Quality of Life of Patients with Cancer: A Determinant of the Quality of Life of Their Family Caregivers

Abstract

Cancer disrupts the quality of life of both the patients and their family caregivers. This study attempted to explore the relationship between the quality of life of cancer patients and their family caregivers and to examine whether the quality of life, age, and gender of the patients contributed to the quality of life of their family caregivers. This correlational study involved 206 pairs of participants consisting of cancer patients and their corresponding family caregivers. The European Organization for the Treatment and Research of Quality of Life Questionnaire C-30 (version 3) was administered on the patients and the Caregiver Quality of Life-Cancer was administered on their family caregivers. The result revealed that social functioning, appetite loss, physical functioning, and gender of the patients contributed significantly to the quality of life of their family caregivers. Implications, shortcomings, and future directions were discussed.

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miR-139 Functions as An Antioncomir to Repress Glioma Progression Through Targeting IGF-1 R, AMY-1, and PGC-1{beta}

Gliomas are the most common primary malignant brain tumor with poor prognosis, characterized by a highly heterogeneous cell population, extensive proliferation, and migration. A lot of molecular mechanisms regulate gliomas development and invasion, including abnormal expression of oncogenes and variation of epigenetic modification. MicroRNAs could affect cell growth and functions. Several reports have demonstrated that miR-139 plays multifunctions in kinds of solid tumors through different pathways. However, the antitumor mechanisms of this miR-139 are not unveiled in detail. In this study, we not only validated the low expression level of miR-139 in glioma tissues and cell lines but also detected the effect of miR-139 on modulating gliomas proliferation and invasion both in vitro and in vivo. We identified insulin-like growth factor 1 receptor, associate of Myc 1, and peroxisome proliferator-activated receptor coactivator 1β as direct targets of miR-139 and the levels of them were all inversely correlated with miR-139 in gliomas. Insulin like growth factor 1 receptor promoted gliomas invasion through Akt signaling and increased proliferation in the peroxisome proliferator-activated receptor coactivator 1β-dependent way. Associate of Myc 1 also facilitated gliomas progression by activating c-Myc pathway. Overexpression of the target genes could retrieve the antitumor function of miR-139, respectively, in different degrees. The nude mice transplantation tumor experiment displayed that glioma cells stably expressed miR-139 growth much slower in vivo than the negative control cells. Taken together, these findings suggested miR-139 acted as a favorable factor against gliomas progression and uncovered a novel regulatory mechanism, which may provide a new evidenced prognostic marker and therapeutic target for gliomas.

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Image-Guided High-Dose Rate Brachytherapy in Cervix Carcinoma Using Balloon Catheter and Belt Immobilization System

Purpose:

The efficacy of image-guided high-dose rate brachytherapy for cervical cancer is limited by the ineffective rectal sparing devices available commercially and the potential applicator movement. We developed a novel device using a balloon catheter and a belt immobilization system, serving for rectal dose reduction and applicator immobilization purposes, respectively.

Methods:

The balloon catheter is constructed by gluing a short inflatable tube to a long regular open-end catheter. Contrast agent (10) cm³ is injected into the inflatable end, which is affixed to the tandem and ring applicator, to displace the posterior vaginal wall. The belt immobilization system consists of a specially designed bracket that can hold and fix itself to the applicator, a diaper-like Velcro fastener package used for connecting the patient's pelvis to the bracket, and a buckle that holds the fasteners to stabilize the whole system. The treatment data for 21 patients with cervical cancer using both balloon catheter and belt immobilization system were retrospectively analyzed. Computed tomography and magnetic resonance images, acquired about 30 minutes apart, were registered to evaluate the effectiveness of the immobilization system.

Results:

In comparison with a virtual rectal blade, the balloon decreased the rectal point dose by 34% ± 4.2% (from 276 ± 57 to 182 ± 38 cGy), corresponding to an extra sparing distance of 7.9 ± 1.1 mm. The maximum sparing distance variation per patient is 1.4 ± 0.6 mm, indicating the high interfractional reproducibility for rectum sparing. With the immobilization system, the mean translational and rotational displacements of the applicator set are <3 mm and <1.5°, respectively, in all directions.

Conclusions:

The rectal balloon provides significant dose reduction to the rectum and it may potentially minimize patient discomfort. The immobilization system permits almost no movement of the applicator during treatment. This work has the potential to be promoted as a standardized solution for high-dose rate treatment of cervical cancer.

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Erratum

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FDA Approves Eribulin Mesylate for Advanced Liposarcoma

The Food and Drug Administration (FDA) approved eribulin mesylate (Halaven®) on January 28 for some patients with liposarcoma. The approval is for patients whose cancers are advanced (metastatic) or cannot be removed by surgery (unresectable) and are no longer responding to anthracycline-based chemotherapy.

"The approval offers a therapeutic option for a disease with minimal treatment options," said Chris Heery, M.D., director of the Clinical Trials Group in NCI's Center for Cancer Research.

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Machine learning-based classification of diffuse large B-cell lymphoma patients by eight gene expression profiles

Abstract

Gene expression profiling (GEP) had divided the diffuse large B-cell lymphoma (DLBCL) into molecular subgroups: germinal center B-cell like (GCB), activated B-cell like (ABC), and unclassified (UC) subtype. However, this classification with prognostic significance was not applied into clinical practice since there were more than 1000 genes to detect and interpreting was difficult. To classify cancer samples validly, eight significant genes (MYBL1, LMO2, BCL6, MME, IRF4, NFKBIZ, PDE4B, and SLA) were selected in 414 patients treated with CHOP/R-CHOP chemotherapy from Gene Expression Omnibus (GEO) data sets. Cutoffs for each gene were obtained using receiver–operating characteristic curves (ROC) new model based on the support vector machine (SVM) estimated the probability of membership into one of two subgroups: GCB and Non-GCB (ABC and UC). Furtherly, multivariate analysis validated the model in another two cohorts including 855 cases in all. As a result, patients in the training and validated cohorts were stratified into two subgroups with 94.0%, 91.0%, and 94.4% concordance with GEP, respectively. Patients with Non-GCB subtype had significantly poorer outcomes than that with GCB subtype, which agreed with the prognostic power of GEP classification. Moreover, the similar prognosis received in the low (0–2) and high (3–5) IPI scores group demonstrated that the new model was independent of IPI as well as GEP method. In conclusion, our new model could stratify DLBCL patients with CHOP/R-CHOP regimen matching GEP subtypes effectively.

To classify diffuse large B-cell lymphoma (DLBCL) samples validly, a classified model based on machine learning was developed by eight significant genes (MYBL1, LMO2, BCL6, MME, IRF4, NFKBIZ, PDE4B, and SLA). As a result, patients in the training and validated cohorts were stratified into two subgroups (GCB and Non-GCB) with 94%, 91%, and 94.4% concordance with gene expression profiling (GEP), respectively. In conclusion, our new model could stratify DLBCL patients with CHOP/R-CHOP regimen matching GEP subtypes effectively.

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Mesenchymal stem/stromal cells—a key mediator for regeneration after perinatal morbidity?

Abstract

Perinatal complications in both term- and preterm-born infants are a leading cause of neonatal morbidities and mortality. Infants face different challenges in the neonatal intensive care unit with long-term morbidities such as perinatal brain injury and bronchopulmonary dysplasia being particularly devastating. While advances in perinatal medicine have improved our understanding of the pathogenesis, effective therapies to prevent and/or reduce the severity of these disorders are still lacking. The potential of mesenchymal stem/stromal cell (MSC) therapy has emerged during the last two decades, and an increasing effort is conducted to address brain- and lung-related morbidities in neonates at risk. Various studies support the notion that MSCs have protective effects. MSCs are an easy source and may be readily available after birth in a clinical setting. MSCs' mechanisms of action are diverse, including migration and homing, release of growth factors and immunomodulation, and the potential to replace injured cells. Here, we review the pathophysiology of perinatally acquired brain and lung injuries and focus on MSCs as potential candidates for therapeutic strategies summarizing preclinical and clinical evidence.

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Acknowledgment of Authors [Acknowledgments]

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Reducing the Time From Diagnosis to Treatment of Patients With Stage II/III Rectal Cancer at a Large Public Hospital [Quality in Action]

Curative-intent therapy for stage II/III rectal cancer is necessarily complex. Current guidelines by the National Comprehensive Cancer Network recommend preoperative concurrent chemoradiation followed by resection and additional adjuvant chemotherapy. We used standard quality improvement methodology to implement a cost-effective intervention that reduced the time from diagnosis to treatment of patients with stage II/III rectal cancer by approximately 30% in a large public hospital in Houston, Texas. Implementation of the program resulted in a reduction in time from pathologic diagnosis to treatment of 29% overall, from 62 to 44 days. These gains were cost neutral and resulted from improvements in scheduling and coordination of care alone. Our results suggest that: (1) quality improvement methodology can be successfully applied to multidisciplinary cancer care, (2) effective interventions can be cost neutral, and (3) effective strategies can overcome complexities such as having multiple sites of care, high staff turnover, and resource limitations.

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Acknowledgment of Reviewers [Acknowledgments]

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Impact of a Palliative Care Checklist on Clinical Documentation [Quality in Action]

Purpose:

Checklists are used in many different settings for the purpose of standardization and reduction of preventable errors in practice. Our group sought to determine whether a palliative care checklist (PCC) would improve the clinical documentation of key patient information.

Methods:

An initial review of 110 randomly selected medical records dictated by 10 physicians was performed. The authors identified portions of the dictated medical records that were included regularly, as well as those that were frequently missed. A PCC was drafted after final approval was obtained from the 13 faculty members. Dictations from 13 clinical faculties in the supportive care center were reviewed. A ² test or Fisher's exact test was applied to assess the difference in overall checked rates before and after checklist use. A paired t test was used to examine the difference in the average complete rate and checked rates before and after checklist use.

Results:

There were improvements in the documentation before and after the checklist for scores on the Cut-down, Annoyed, Guilty, Eye-opener questionnaire for alcoholism (79% v 94%; P ≤ .0001), psychosocial history (69% v 95%; P ≤ .0001), Eastern Cooperative Oncology Group performance status (38% v 81%; P ≤ .0001), advance care planning (28% v 41%; P = .0008), and overall (78% v 95%; P ≤ .0001). There was no significant improvement in the documentation for opioid-induced neurotoxicity (37% v 37%; P = .9492) or the Edmonton Symptom Assessment Scale (98% v 99%; P = .4511).

Conclusion:

Our study showed that the use of a PCC improved the quality of the documentation of a patient visit in an outpatient clinical setting.

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Development of a Cancer Care Summary Through the Electronic Health Record [Quality in Action]

Introduction:

Our objective was to improve communication concerning lung cancer patients by developing and distributing a Cancer Care Summary that would provide clinically useful information about the patient's diagnosis and care to providers in diverse settings.

Methods:

We designed structured, electronic forms for the electronic health record (EHR), detailing tumor staging, classification, and treatment. To ensure completeness and accuracy of the information, we implemented a data quality cycle, composed of reports that are reviewed by oncology clinicians. The data from the EHR forms are extracted into a structured query language database system on a daily basis, from which the Summaries are derived. We conducted focus groups regarding the utility, format, and content of the Summary. Cancer Care Summaries are automatically generated 4 months after a patient's date of diagnosis, then every 6 months for those receiving treatment, and on an as-needed basis for urgent care or hospital admission.

Results:

The product of our improvement project is the Cancer Care Summary. To date, 102 individual patient Summaries have been generated. These documents are automatically entered into the National Jewish Health (NJH) EHR, attached to correspondence to primary care providers, available to patients as electronic documents on the NJH patient portal, and faxed to emergency departments and admitting physicians on patient evaluation.

Conclusion:

We developed a sustainable tool to improve cancer care communication. The Cancer Care Summary integrates information from the EHR in a timely manner and distributes the information through multiple avenues.

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Improving Chemotherapy Ordering Process [Quality in Action]

Purpose:

Chemotherapy is a high-risk medication and is the second most common cause of fatal medication errors. The ordering process can be unsafe and inefficient, putting patients at risk for medication errors. The aim of this project was to decrease the number of chemotherapy order forms with at least one deviation by 50% within 5 months.

Methods:

A multidisciplinary team identified causes for variance in form completion, deficits in knowledge of ordering processes, and acceptance of incomplete orders by the staff. The Plan, Do, Study, Act improvement methodology evaluated the chemotherapy ordering process and found different types of deviations on order forms. Interventions consisted of educating physicians on entering complete information on orders, instituting same-day laboratory work on the day of the physician's visit, standardizing laboratory parameters, performing audits of the order forms manually, and educating nurses on not accepting orders with deviations.

Results:

All order forms were reviewed, and data were collected on different types of deviations. The following deviations were identified: laboratory test results were not being entered into the order form within 7 days, physicians were not providing their name and pager number, and the days of the chemotherapy cycle were missing from the order forms. Before the intervention, 70.1% of the chemotherapy order forms had at least one deviation. After 5 months of interventions, there was a reduction of 19% in the number of order forms with at least one deviation. Follow-up at 6 months and 1 year showed continuing reductions in the number of chemotherapy orders with at least one deviation.

Conclusion:

Improvement was a result of collaboration between interdisciplinary departments. The original goal was surpassed as a result of educating physicians and staff and standardizing the ordering process. If the number of deviations in chemotherapy order forms is decreased, oncology patients will receive safe, efficient, and quality care.

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Meningeal Myelomatosis [Case Report]

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ReCAP: Comparison of Independent Error Checks for Oral Versus Intravenous Chemotherapy [CARE DELIVERY]

QUESTION ASKED:

In the United States, research has found that oral chemotherapy is subject to fewer safeguards than are in routine use for intravenous (IV) chemotherapy; however, less is known about the Canadian context. The objective of this study was to determine whether similar safeguards, in the form of independent checks, existed to identify potential errors related to IV and oral chemotherapy formulations in a particular cancer system.

SUMMARY ANSWER:

In the cancer system studied, a total of 57 systematic checks were identified for IV chemotherapy, whereas only six systematic checks were identified for oral chemotherapy. Community pharmacists were the only qualified professionals involved in independent, systematic checking of oral chemotherapy, which occurred during ordering and dispensing.

METHODS:

Human factors specialists conducted observations and interviews in cancer center clinics, a cancer center pharmacy, and four community pharmacies across Nova Scotia. Processes were analyzed to determine whether an independent check was performed, which qualified provider completed the check, and at what point of the process the check occurred.

BIAS, CONFOUNDING FACTOR(S), DRAWBACKS:

This study had some limitations. Although there are many forms of safeguards (eg, preprinted orders), only one type of safeguard (ie, independent checks) was examined in the cancer system studied. We chose to focus on independent checks because they were observable and were defined in the cancer center's policies. Another limitation was that just a single jurisdiction (Nova Scotia), and four community pharmacies were examined. We examined each community pharmacy in detail, and sites were chosen to be representative (eg, rural versus urban). Further, the model used to deliver oral chemotherapy in Nova Scotia is not unique; a number of other provinces share similar models.

REAL-LIFE IMPLICATIONS:

There is an enormous opportunity for pharmacists and other qualified professionals to take on an expanded role in improving patient safety for oral chemotherapy. Oral chemotherapy, like IV chemotherapy, is known to be potentially hazardous, but in the cancer system studied, there were dramatically fewer independent checks associated with all aspects of oral chemotherapy–related processes. Greater involvement of pharmacists, both in the clinic environment and the community, would facilitate increased systematic checking, which could improve patient safety related to oral chemotherapy.

FIG 2.

Systematic checks conducted by qualified health care practitioners across planning, ordering, dispensing, and administration of oral and intravenous (IV) chemotherapies. RNCC, chemotherapy-certified registered nurse.

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Breast Cancer in Women Older Than 80 Years [Clinical Reviews]

Breast cancer is the most common cancer in women, with an incidence that rises dramatically with age. The average age at diagnosis of breast cancer is 61 years, and the majority of woman who die of breast cancer are age 65 years and older. Major improvements in public health and medical care have resulted in dramatic increases in longevity. The oldest old (those age 80 years and older) are a rapidly expanding group and now comprise 9 million members of the US population. The treatment of individuals who are age 80 years and older is complex and involves clearly defining the goals and value of treatment while also weighing risks, such as the potential effects of treatment on functional loss and quality of life. Limited evidence-based treatment guidelines exist for the caring of this older cohort of patients with breast cancer. Data from clinical trials that enroll primarily younger patients lack the information needed to estimate the likelihood of toxicities that can be life changing in older adults. Clinicians who make treatment recommendations should place the available evidence in the context of the patient's life expectancy and geriatric assessment results that include an evaluation of a patient's functional status, comorbidities, cognition, social support, nutritional status, and psychological state. Furthermore, these decisions should be placed in the context of the patient's goals for treatment, preferences, and values. This review summarizes the current literature and focuses on the role of geriatric assessment in treatment recommendations for patients age 80 years and older with early and metastatic breast cancer.

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Treatment of Breast Cancer in Women Older Than 80 Years Is a Complex Task [COMMENTARIES]

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ReCAP: Feasibility and Effectiveness of a Pilot Program to Facilitate Quality Improvement Learning in Oncology: Experience of the American Society of Clinical Oncology Quality Training Program [FOCUS ON QUALITY]

CONTEXT AND QUESTION ASKED:

Improving quality of oncology delivery is an important responsibility for busy oncology practices. Is it feasible to construct a training program for oncology professionals to teach quality improvement that is applicable to practice?

SUMMARY ANSWER:

Using a longitudinal, project-based program with a mix of in-person and distance-learning components, the ASCO Quality Training Program is a highly feasible method to facilitate quality improvement learning in oncology.

METHODS:

The ASCO Quality Training Program (QTP) consisted of three in-person Learning Sessions and four phases: pre-work, planning, implementation, and sustain and spread. We measured two primary outcomes: program feasibility and effectiveness.

BIAS, CONFOUNDING FACTOR(S), DRAWBACKS:

Although we observed high participation, satisfaction, and applicability of content to the needs of the oncology learners, it should be noted that this represents a small, pilot project.

REAL-LIFE IMPLICATIONS:

Even busy oncology clinicians find a structured program to learn and practice quality improvement skills valuable. Conclusions regarding long-term applicability effectiveness and feasibility among non-early adopters require further study.

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Geriatricizing Oncology Care: Older Women With Breast Cancer [COMMENTARIES]

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ReCAP: Feasibility and Accuracy of Extracting Cancer Stage Information From Narrative Electronic Health Record Data [CARE DELIVERY]

QUESTION ASKED:

Cancer stage, one of the most important prognostic factors for cancer-specific survival, is often documented in narrative form in electronic health records (EHRs), and as such is difficult to abstract by registrars and other secondary data users, including clinicians participating in quality reporting activities. Can the cancer stage be accurately extracted by natural language processing (NLP) of the text from EHRs?

SUMMARY ANSWER:

In a combined dataset of N = 2,323 patients with lung cancer (training set: n = 1,103; validation set n = 1,220), we analyzed 751,880 documents and discovered at least one stage statement for 98.6% of patients (median of 24 documents with stage statements per patient). Despite a high degree of discordance in patient records (83.6% of patients had conflicting stage statements in their HER; Fig 2), algorithmically derived stage accuracy was very high in the validation set, = 0.906 (95% CI, 0.873 to 0.939), as compared with the gold standard of tumor registrar–derived stage.

METHODS:

We developed an NLP algorithm to extract stage statements from machine-readable EHR documents, including automated rules to choose the most likely stage when discordance was present in the EHR; the algorithm was developed on a training set of patients with lung cancer and independently validated on a test set of patients with lung cancer who were seen at our institution.

BIAS, CONFOUNDING FACTOR(S), DRAWBACKS:

An exact stage (eg, stage I, stage IV) could be calculated for only 72% of the patients; the remainder were assigned an inexact stage (eg, "early stage"). In an exploratory analysis, we were able to distinguish stage IIIA from stage IIIB, but the accuracy was not as good, in the 64% to 79% range. The experiments were carried out only on patients with lung cancer, so it is unknown whether other tumor types would have a similar level of performance. We did not explicitly consider the provenance of the information, (eg, was the stage documented by a medical student, an attending oncologist, etc). Finally, given that this was performed at a single tertiary care institution, there may be significant differences in documentation patterns at other institutions that could affect the reproducibility of the results.

REAL-LIFE IMPLICATIONS:

This new approach to the determination of summary stage in patients with lung cancer can be applied rapidly and broadly to a patient population with large amounts of EHR data. Despite the presence of significant discordance in documentation, the results were highly accurate. This proof-of-concept suggests that NLP may augment and enhance manual abstraction efforts and may even replace them for certain targeted applications.

FIG 2.

Network diagram of stage co-occurrences found in individual patient records. Circles represent network nodes, which are proportionate to the number of times that a particular stage category is mentioned across all patients. Lines between nodes represent network edges, with width proportionate to the number of times that a particular co-occurrence is observed across all patients.

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Cancer Staging in Electronic Health Records: Strategies to Improve Documentation of These Critical Data [Editorials]

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ReCAP: Would Women With Breast Cancer Prefer to Receive an Antidepressant for Anxiety or Depression From Their Oncologist? [CARE DELIVERY]

QUESTIONS ASKED:

Preferences of patients with breast cancer for provider-specific pharmacologic management of anxiety and depression are unknown. Use of patient-guided treatment preferences for the treatment of depression and anxiety are known to improve adherence and treatment outcomes in primary care settings, but these preferences are not known in women with breast cancer. This may be especially true shortly after the patient receives a diagnosis of cancer and is most psychologically symptomatic, yet committed to following through with her oncologic care. Do breast cancer patients have preferences regarding having their anxiety and depression assessed and treated by their oncologists versus being cared for by a psychiatrist or mental health provider?

SUMMARY ANSWER:

The majority of patients accepted antidepressant prescribing by their oncologist; only a minority preferred treatment by a mental health professional. These findings are consistent with previous data from medically ill patients that demonstrated a preference for medical providers to address and treat their depression or anxiety. Twenty percent of participants would not want any treatment. Patients who met depression criteria were less likely to prefer a mental health referral. Patients who were already taking an antidepressant or demonstrated higher levels of chronic stress were more likely to prefer a mental health referral.

METHODS:

Patients with breast cancer (stages 0-IV) were asked two questions: (1) "Would you be willing to have your oncologist treat your depression or anxiety with an antidepressant medication if you were to become depressed or anxious at any point during your treatment?" and (2) "Would you prefer to be treated by a psychiatrist or mental health professional for problems with either anxiety or depression?" In addition, the Distress Thermometer and Problem List, Hospital Anxiety and Depression Scale, Risky Families Questionnaire, and demographic information were assessed.

BIAS, CONFOUNDING FACTORS, DRAWBACKS:

This was a survey of only women who were asked to self-report hypothetical preferences. Although minimal differences were noted for the 16.8% of participants who were already taking an antidepressant medication, it is not clear how they might have interpreted the questions in a more realistic setting.

REAL-LIFE IMPLICATIONS:

These findings suggest a benefit for promoting education of oncologists to assess psychological symptoms and manage anxiety and depression as a routine part of an outpatient visit. It highlights a fertile opportunity for oncologists to integrate mental health treatment for their patients by beginning pharmacologic treatment, discussing their anxiety or depressive symptoms, and initiating or comanaging pharmacologic treatment of anxiety or depression. Early recognition and management of distress, anxiety, and depression would limit the delay in obtaining appropriate treatment, especially during the first year after a cancer diagnosis when patients are most symptomatic and have many difficult treatment decisions to make. The oncologist's use of antidepressant medications to treat anxiety and depression may benefit patients most by following guidelines. A collaborative care model offers one potential solution that could establish ownership, expand resources, disseminate knowledge, and provide a system of integration for mental health and oncology providers.

Table 1.

Cohort Characteristics and Preference for Oncologist Versus Mental Health Care Provider

Preference for Oncologist (n = 111)Preference for Psychiatrist/Mental Health Provider (n = 118)CharacteristicYes (n = 67; 60.4%)No (n = 44; 39.6%)Yes (n = 31; 26.3%)No (n = 44; 37.3%)Does Not Matter (n = 43; 6.4%)No.%No.%²pNo.%No.%No.%²pRace/ ethnicity Black or African American1218.201328.301.99.58412.91023.31024.410.15.12 White3756.102145.7022711848.92151.2 Latino1015.20817.80412.91125.64.09.8 Other710.6048.7013.249.3614.6Married3553.002143.800.96.331238.722502559.53.10.21Working3672.002363.900.64.422275.921751961.351.94.38Lumpectomy2437.552554.303.08.081346.41841.91947.50.30.86Mastectomy3654.502043.501.33.251344.82455.81946.31.10.58Chemotherapy3858.502756.300.06.812064.52556.82356.10.61.74Receiving anti-hormones3961.902043.503.64.061758.61945.22357.51.71.43Taking antidepressant1218.20918.800.01.941135.5613.6511.97.73.02*Distress Screen (DT&PL ≥4) n = 44 (55.1%)3054.502055.600.01.931659.32362.21445.22.16.34Distress Screen (DT&PL ≥7) n = 17 (17.2%)916.40616.700.00.9727.4924.3619.43.11.21Anxiety Screen (HADS-A ≥ 8), n = 46 (36.8%)2538.501634.000.23.631343.31432.61740.50.01.61Depression Screen (HADS-D ≥ 8), n = 25
(20.8%)1320.00817.000.16.69413.3818.61023.81.25.53MeanSDMeanSDTpMeanSDMeanSDMeanSDFpAge, years55.013.8956.213.080.47.6453.614.757.812.154.213.91.10.34Distress (DT&PL, range 0-10)3.92.333.81.95-0.10.924.22.04.33.03.42.51.15.32Anxiety (HADS-A, range 0-21)6.14.445.83.51-0.38.716.73.85.64.06.44.40.68.51Depression (HADS-D, range 0-21)3.53.914.43.321.23.223.73.73.93.74.13.90.12.89Chronic Stress (RFQ, range 13-65)23.611.8123.67.640.03.9826.8*9.120.5*8.224.012.03.60.03*

Abbreviations: DT&PL, Distress Thermometer and Problem List; HADS-A, Hospital Anxiety and Depression Scale-Anxiety; HADS-D Hospital Anxiety and Depression Scale-Depression; RFQ, Risky Families Questionnaire; SD, standard deviation.

*

p < .05.

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Benefits and Pitfalls of Using Administrative Data to Study Hospitalization Patterns in Patients With Cancer Treated With Chemotherapy [Editorials]

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Extended RAS Gene Mutation Testing in Metastatic Colorectal Carcinoma to Predict Response to Anti-Epidermal Growth Factor Receptor Monoclonal Antibody Therapy: American Society of Clinical Oncology Provisional Clinical Opinion Update 2015 Summary [ASCO Special Article]

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Refining the Standard of Care: How Oncology Treatment Pathways Can Make a Difference [Editorials]

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ReCAP: Impact of Multidisciplinary Care on Processes of Cancer Care: A Multi-Institutional Study [CARE DELIVERY]

QUESTION ASKED:

What is the relationship between the level of implementation of multidisciplinary care (MDC) and various processes of cancer care (eg, time to treatment receipt, evaluation for enrollment onto a clinical trial) among community cancer centers serving patients diagnosed with colon, rectal, or lung cancer? There is limited generalizable evidence on this topic. It is important to answer this question using data that can generalize across cancer patients, the majority of whom receive treatment in a community cancer center.

SUMMARY ANSWER:

Focusing on the time to receipt of cancer-directed treatment as one key process of cancer care in this patient population, we found that the answer to our question depended on the MDC assessment area and tumor site (Table 1). Among patients with colon cancer, higher MDC levels of physician engagement (ie, a higher level of physician engagement at the institutional level) were associated with a shorter time to treatment receipt, whereas higher MDC levels of case planning were associated with a longer time to treatment receipt. Among patients with rectal cancer, higher MDC levels of physician engagement were associated with a shorter time to cancer-directed treatment receipt, whereas higher MDC levels of evaluation for enrollment onto clinical trials were associated with a longer time to treatment receipt. Among patients with lung cancer, there was no association between the MDC areas of assessment and the time to cancer-directed treatment receipt.

Table 1.

Multivariable Analyses of the Associations Between MDC Implementation and Time to Cancer-Directed Treatment Receipt

VariableLung (n = 560)*Colon (n = 378)*Rectal (n = 141)*HR95% CIHR95% CIHR95% CICase planning    LowReferenceReferenceReference High0.780.471.280.650.490.851.260.662.42Physician engagement    LowReferenceReferenceReference    Moderate0.870.481.581.501.191.892.611.066.44    High0.980.462.102.661.704.174.871.4116.78Care coordination    LowReferenceReferenceReference    Moderate0.780.551.110.670.371.231.260.752.12    High0.640.241.690.550.271.100.360.111.15Clinical trial    LowReferenceReferenceReference    High0.880.571.361.480.842.580.54*0.310.95

NOTE. Hazard ratios were adjusted for patient clinical and demographic measures: age, race, ethnicity, diagnosis year, gender, and cancer center geographic classification (rural/urban). The final specification of each multivariate regression model varied with the disease site and outcome measure due to differences in sample sizes and in the performance of the statistical models (eg, model fit, convergence).

Abbreviations: HR, hazard ratio (covariate adjusted); MDC, multidisciplinary care.

*

Controlling for age, year of diagnosis, gender, cancer center location and race.

P < .05.

P< .001.

METHODS:

We collected data for patients receiving care at 14 National Cancer Institute (NCI) community cancer centers. We characterized the NCI community cancer centers according to their level of MDC implementation across seven MDC assessment areas and over time. Using statistical regression models, we investigated the relationship between the level of MDC implementation and various process measures, including time to treatment receipt, clinical trial evaluation, receipt of multimodality treatment, and adherence to treatment guidelines published by the National Comprehensive Cancer Network.

BIAS, CONFOUNDING FACTOR(S), DRAWBACKS:

In the absence of a validated MDC assessment tool, the NCI community cancer centers used a nonvalidated tool. Additional institutional-level data would have been useful for characterizing norms and practices that may have differed across cancer centers and potentially explained variation in care processes. Although we controlled for patient demographic characteristics, baseline data were not available to document patient comorbidity or performance status level. To the extent that cancer centers at higher levels of MDC implementation may have been more likely to treat clinically complex patients, the inability to control for potential confounding bias caused by patient case mix may have influenced the study results.

REAL-LIFE IMPLICATIONS:

MDC models are important decision-making forums in current oncology practice. They involve oncologists in generating a comprehensive and coordinated plan of care for patients. Although MDC is purported to offer benefits to patients, there is limited generalizable evidence regarding the benefit to individuals receiving care at community cancer centers in the United States. Across various care processes that are important for characterizing cancer care, this study's results indicate that changes in the level of MDC implementation could differentially affect the process of care, depending on the MDC area of assessment and the cancer site. In addition, the study results can be used to generate hypotheses for future studies among individuals diagnosed with colon, rectal, or lung cancer.

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ReCAP: ASCO Core Curriculum for Cancer Survivorship Education [CARE DELIVERY]

CONTEXT AND QUESTION(S) ASKED:

The number of cancer survivors is increasing exponentially. Currently there about 15 million cancer survivors, and by 2025, there will be nearly 20 million. Who will provide survivorship care, what are evidenced-based or best care practices, what are best methods to disseminate this information and assess its impact on physician practice, and what are the most cost-effective health care delivery models to serve the majority of survivors?

SUMMARY ANSWER:

The ASCO Survivorship Committee in collaboration with the ASCO Professional Development Committee developed a core curriculum and core competencies for physicians, allied health professionals, training programs, and policymaking organizations. Adapted from Institute of Medicine recommendations for survivorship care, the core curriculum and competencies include the following subheadings: surveillance for recurrence and second malignancies, long-term and late effects, health promotion and prevention, psychosocial well-being, special populations including adolescent and young adult survivors, older adult cancer survivors, caregivers of cancer survivors and communication and care coordination.

METHODS:

An environmental scan (a process that systematically surveys and interprets relevant data to identify opportunities and barriers) for survivorship was performed. Although survivorship content exists in various courses, conferences, guidelines, and Web-based applications, the information is incomplete and not easily found. Hence, there was a need for this content to be easy to access and available in one place. Content experts formulated the individual sections based on the environmental scan and their knowledge of the various subheadings.

BIAS, CONFOUNDING FACTOR(S), DRAWBACKS:

Both an environmental scan and a comprehensive literature review have standard methodologies. The differences are in scope; an environmental scan is more like an overview, and the standard literature review is more granular. For this article, we felt that environmental scan better served the purpose of developing a survivorship core curriculum and competencies.

REAL-LIFE IMPLICATIONS:

Survivorship care is one the most challenging problems oncologists face today and in the near future. Fundamental to the relatively new field of survivorship care is this core curriculum and competencies, which provide the framework necessary to generate appropriate referrals depending on local practices and expertise.

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The Use of Anatomical Information for Molecular Image Reconstruction Algorithms: Attenuation/Scatter Correction, Motion Compensation, and Noise Reduction

Abstract

PET and SPECT are important tools for providing valuable molecular information about patients to clinicians. Advances in nuclear medicine hardware technologies and statistical image reconstruction algorithms enabled significantly improved image quality. Sequentially or simultaneously acquired anatomical images such as CT and MRI from hybrid scanners are also important ingredients for improving the image quality of PET or SPECT further. High-quality anatomical information has been used and investigated for attenuation and scatter corrections, motion compensation, and noise reduction via post-reconstruction filtering and regularization in inverse problems. In this article, we will review works using anatomical information for molecular image reconstruction algorithms for better image quality by describing mathematical models, discussing sources of anatomical information for different cases, and showing some examples.

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Erratum to: SEOM guidelines for the treatment of gastric cancer 2015

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Carfilzomib combined with suberanilohydroxamic acid (SAHA) synergistically promotes endoplasmic reticulum stress in non-small cell lung cancer cell lines

Abstract

Purpose

The endoplasmic reticulum (ER) stress response is a therapeutic target for pharmacologic intervention in cancer cells. We hypothesized that combining carfilzomib (CFZ), a proteasome inhibitor, and vorinostat (SAHA), a histone deacetylase (HDAC) inhibitor, would synergistically activate ER stress in non-small cell lung cancer (NSCLC) cell lines, resulting in enhanced anti-tumor activity.

Methods

Five NSCLC cell lines were treated with CFZ, SAHA, or the combination and cell proliferation measured using the MTT assay. Calcusyn software was utilized to determine the combination index as a measure of synergy. Cell viability and cytotoxicity were measured using trypan blue exclusion, CellTiter, and CytoTox assays. Western blot was used to measure markers of apoptosis, ER stress, and oxidative stress-related proteins. Reactive oxygen species (ROS) was measured using the fluorophore CM–H₂DCFDA.

Results

Synergistic activity was observed for all cell lines following 48 and 72 h of combined treatment. H520 and A549 cell lines were used to assess viability and apoptosis. In both cell lines, increased death and cleaved caspase-3 were observed following combination treatment as compared with single-agent treatments. Combination therapy was associated with upregulation of ER stress-regulated proteins including activating transcription factor 4, GRP78/BiP, and C/EBP homologous protein. Both cell lines also showed increased ROS and the oxidative stress-related protein, heat shock protein 70.

Conclusion

Combining proteasome inhibition with HDAC inhibition enhances ER stress, which may contribute to the synergistic anticancer activity observed in NSCLC cell lines. Further preclinical and clinical studies of CFZ + SAHA in NSCLC are warranted.

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Demographic, tumor and clinical features of clinical trials versus clinical practice patients with HER2-positive early breast cancer: results of a prospective study

Abstract

Background

Several randomized clinical trials (RCTs) have demonstrated the efficacy of trastuzumab-based adjuvant therapy in HER2-positive breast cancer (BC). However, RCT patients may not invariably be representative of patients routinely seen in clinical practice (CP). To address this issue, we compared the clinical and tumor features of RCT and CP patients with HER2-positive BC.

Patients and methods

From January to December 2012, 650 consecutive patients with HER2-positive early BC, treated in 36 different types of Italian healthcare facilities, were enrolled in this study. Age, treatment, tumor size (T), nodes (N), grade (G), estrogen receptor (ER) and progesterone receptor (PgR) status were prospectively collected in these CP patients. The same data were extracted from the main adjuvant trastuzumab RCTs and pooled using the random-effects model of DerSimonian and Laird. RCT and CP patients were compared by using the Cochran Q statistics.

Results

Versus RCT patients, CP patients were more likely to be older than 50 years (65 vs. 49 %; p < 0.0001) and to have HR (ER and/or PgR)-positive (72 vs. 54 %; p < 0.0001) BC and less likely to have tumor >2 cm (T ≥ 2 cm 39 vs. 59 %; p < 0.0001), positive N (47 vs. 89 %; p < 0.0001) and a high G (61 vs. 67 %; p = 0.0241). CP patients more frequently received adjuvant endocrine therapy (70 vs. 57 %; p < 0.0003) and less frequently adjuvant chemotherapy (97 vs. 99.7 %; p < 0.0001).

Conclusions

Most tumor and clinical features differed significantly between CP and RCT patients. These data raise concerns about the applicability of RCT results to CP patients.

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Upregulation of nuclear transporter, Kpnβ1, contributes to accelerated cell proliferation- and cell adhesion-mediated drug resistance (CAM-DR) in diffuse large B-cell lymphoma

Abstract

Background

The Karyopherin proteins are involved in the shuttling of cargo proteins, and certain RNAs, across the nuclear pore complex into and out of the cell nucleus. Karyopherin β1 (Kpnβ1) is a member of the Karyopherin β superfamily of nuclear transport proteins. In addition to the nuclear import function, Kpnβ1 is associated with the occurrence of tumors. This study investigated the expression and biologic function of Kpnβ1 in diffuse large B-cell lymphoma (DLBCL).

Methods

The prognostic value of Kpnβ1 expression was evaluated using immunohistochemical staining. The role of Kpnβ1 on cell proliferation- and cell adhesion-mediated drug resistance (CAM-DR) was also determined.

Results

We demonstrated that Kpnβ1 mRNA and protein expression levels were significantly higher in DLBCL B-cells and DLBCL cell lines than in normal CD19 purified B-cells. Immunohistochemical analysis suggested that the expression of Kpnβ1 was correlated with Ki-67 (P < 0.001). Kaplan–Meier curve showed that high expression of Kpnβ1 was significantly associated with shorter overall survival. In addition, Kpnβ1 was associated with the proliferation of DLBCL cells. Importantly, we found that Kpnβ1 could interact with p65 and promote CAM-DR via accelerating NF-κB activation in DLBCL.

Conclusions

Patients with tumors highly expressing Kpnβ1 have poorer overall survivals. Kpnβ1 interacts with p65 and enhances CAM-DR.

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MicroRNA-206 functions as a tumor suppressor in colorectal cancer by targeting FMNL2

Abstract

Background

Colorectal cancer (CRC) is one of the most common cancers in the world. MicroRNAs play important roles in the progression of CRC. This study aimed to investigate the role of miR-206 and its novel mechanism in the invasion and metastasis of CRC.

Methodology

Real-time RT-PCR or Western blotting was used to detect the expressions of miR-206, FMNL2 and c-MET in CRC cell lines and tissues. Luciferase reporter assays were conducted to detect the associations between miR-206 and 3′UTRs of FMNL2 and c-MET. A series of loss-of-function and gain-of-function assays were performed to evaluate the effect of miR-206 on the proliferation, invasion and metastasis of CRC cells.

Results

miR-206 was significantly down-regulated in CRC tissues and correlated closely with differentiation, lymphatic metastasis and serosal invasion. miR-206 suppressed CRC cell proliferation by arresting CRC cells in the G1/G0 phase and accelerating apoptosis. miR-206 also inhibited cell invasion and lung metastasis in CRC cells. Mechanically, FMNL2 and c-MET were identified as direct targets of miR-206. And FMNL2 rescued the suppression of miR-206 in the proliferation and invasion of CRC cells.

Conclusions

This study revealed functional and mechanistic links between miR-206 and oncogene FMNL2 and c-MET in the progression of CRC. miR-206 functioned as a tumor suppressor in the progression of CRC by targeting FMNL2 and c-MET. Restoration of miR-206 expression may represent a promising therapeutic approach for targeting malignant CRC.

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Unique intravascular tumor microenvironment predicting recurrence of lung squamous cell carcinoma

Abstract

Purpose

Histological vascular invasion (VI) by tumors is a risk factor for recurrence after surgical resection. However, VI features vary histologically. The aim of this study was to identify characteristic VI features that are associated with recurrence in squamous cell carcinoma (SCC) of the lung.

Methods

We enrolled 149 patients with pathological stage I primary lung SCC in this study and examined whether the presence, frequency, and size of VI were associated with recurrence. We also evaluated immunophenotypes of carcinoma cells and stromal cells within VI areas.

Results

Of the 149 patients, 58 had tumors with VI. The presence of VI was significantly correlated with shorter recurrence-free survival (RFS) (P = 0.018). Although VI frequency was not associated with RFS, larger VI size (>425 µm) was significantly correlated with shorter RFS (P = 0.003). Carcinoma cells within larger VI areas expressed significantly higher levels of podoplanin, cancer stem cell marker (P = 0.039); higher numbers of CD34⁺ microvessels (P = 0.009), CD204⁺ macrophages (P = 0.026), and α-SMA⁺ myofibroblasts (P = 0.056) were present within larger VI areas than within smaller VI ones.

Conclusions

Our results indicate that larger VI areas are a predictor for recurrence in lung SCC; also, within the larger blood vessel, cancer stem cells and abundant stromal cells can create a more favorable microenvironment for tumor metastasis.

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Treatment results of alternating chemoradiotherapy followed by proton beam therapy boost combined with intra-arterial infusion chemotherapy for stage III–IVB tongue cancer

Abstract

Purpose

Proton beam therapy (PBT), compared with conventional radiotherapy, can deliver high-dose radiation to a tumor, while minimizing doses delivered to surrounding normal tissues. The better dose distribution of PBT may contribute to the improvement in local control rate and reduction in late adverse events. We evaluated therapeutic results and toxicities of PBT combined with selective intra-arterial infusion chemotherapy (PBT-IACT) in patients with stage III–IVB squamous cell carcinoma of the tongue.

Materials and methods

After 2 systemic chemotherapy courses and whole-neck irradiation (36 Gy in 20 fractions), we administered concurrent chemoradiotherapy comprising PBT for the primary tumor [28.6–33 Gy(RBE) in 13–15 fractions] and for the metastatic neck lymph node [33–39.6 Gy(RBE) in 15–18 fractions] with weekly retrograde intra-arterial chemotherapy by continuous infusion of cisplatin with sodium thiosulfate.

Results

Between February 2009 and September 2012, 33 patients were enrolled. The median follow-up duration was 43 months. The 3-year overall survival, progression-free survival, local control rate, and regional control rate for the neck were 87.0, 74.1, 86.6, and 83.9 %, respectively. Major acute toxicities >grade 3 included mucositis in 26 cases (79 %), neutropenia in 17 cases (51 %), and dermatitis in 11 cases (33 %). Late grade 2 osteoradionecrosis was observed in 1 case (3 %).

Conclusions

PBT-IACT for stage III–IVB tongue cancer has an acceptable toxicity profile and showed good treatment results. This protocol should be considered as a treatment option for locally advanced tongue cancer.

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Comparison of the Glasgow Prognostic Score (GPS) and the modified Glasgow Prognostic Score (mGPS) in evaluating the prognosis of patients with operable and inoperable non-small cell lung cancer

Abstract

Purpose

The Glasgow Prognostic Score (GPS) and modified Glasgow Prognostic Score (mGPS) are shown to be reliable prognostic indexes in patients with operable and inoperable non-small cell lung cancer (NSCLC). Considering the difference between the two indexes lies in whether hypoalbuminemia without an elevated C-reactive protein (CRP) is associated with worse survival, this study aims to evaluate the prognostic performance of hypoalbuminemia in patients without an elevated CRP and to compare the prognostic value of GPS and mGPS in patients with operable and inoperable NSCLC.

Methods

The data of 2988 patients were retrospectively collected from the Shanghai Health Information Network. Univariate and multivariate Cox regression was performed to investigate the prognostic effect of albumin, CRP, GPS and mGPS. Restricted cubic spline was also performed to evaluate the relationship between albumin and hazard ratio. Kaplan–Meier survival curves were estimated and compared using the log-rank test. Additional discriminative ability of GPS and of mGPS was evaluated using the area under the curve and Harrell's concordance index.

Results

Hypoalbuminemia was associated with worse survival in both operable and inoperable patients without an elevated CRP. The Kaplan–Meier survival curve of hypoalbuminemic patients without an elevated CRP was more close to the curve of patients with an elevated CRP and a normal albumin than to the curve of patients with neither of these abnormalities. Multivariate analysis, AUC and C-index all indicated that GPS had a higher prognostic value than mGPS.

Conclusions

Hypoalbuminemia was associated with worse survival in patients with or without an elevated CRP. GPS was superior to mGPS in predicting survival in operable and inoperable NSCLC patients.

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The expanding role of metformin in cancer: an update on antitumor mechanisms and clinical development

Abstract

Metformin has been used for nearly a century to treat type 2 diabetes mellitus. Epidemiologic studies first identified the association between metformin and reduced risk of several cancers. The anticancer mechanisms of metformin involve both indirect or insulin-dependent pathways and direct or insulin-independent pathways. Preclinical studies have demonstrated metformin's broad anticancer activity across a spectrum of malignancies. Prospective clinical trials involving metformin in the chemoprevention and treatment of cancer now number in the hundreds. We provide an update on the anticancer mechanisms of metformin and review the results thus far available from prospective clinical trials investigating metformin's efficacy in cancer.

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Erratum to: SEOM guidelines for the treatment of gastric cancer 2015

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Knowledge and Attitudes About Oral Cancer Among Dental Students After Bologna Plan Implementation

Abstract

Oral cancer is the most common of head and neck tumours. Dentists have an important role in the most effective prevention measures: controlling aetiological factors and early detection. Dental curriculum has suffered changes in their structures and contents during Bologna process. The aim of this study is to explore oral cancer knowledge and attitudes among dental students of Granada after the implementation of the Bologna plan. A cross-sectional study was carried out in the School of Dentistry of the University of Granada. A questionnaire was delivered to dental students in the fourth and fifth years (of study) to assess knowledge and attitudes about oral cancer area. 79.3 % related that they examined the oral mucosa from their patients regularly. Almost the whole sample (95.9 %) said that they would advise their patients about risk factors for oral cancer when they graduated. Tobacco followed by alcohol was the main oral cancer risk factor identified (94.2 and 72.7 %, respectively). 96.7 % of the sample would like to receive more information about this subject. Fourth year students had taught self-examination for early detection of oral cancer more frequently than fifth year students (42.5 versus 22.9 %, respectively). The results of this study revealed that dental students had good attitudes in the area of oral cancer. On the other hand, it highlights the need for an improvement of the teaching program regarding risk factors for oral cancer and performing routine oral examination.

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Bizarre parosteal osteochondromatous proliferation in the lingual area of the mandibular body versus osteochondroma at the mandibular condyle

Abstract

Background

Bizarre parosteal osteochondromatous proliferation (BPOP) is benign and usually occurs in the small tubular bones of the hands and feet, but it is extremely rare in the oral and maxillofacial region.

Methods

The present study compares a case of BPOP occurring in the lingual area of the right mandibular body with a representative case of osteochondroma occurring in the left mandibular condyle using immunohistochemical methods.

Results

BPOP showed no continuity to the cortical bone of the mandible on X-ray and was histologically composed of immature cartilage and bone tissues, whereas osteochondroma showed overgrowth of hypertrophic chondrocytes accompanied by mature bone with endochondral ossification. Although BPOP showed no features of cellular atypia or malignant transformation, it expressed more osteogenic proteins, including BMP-2, BMP-4, RUNX2, OC, AP, OPG, RANKL, CTGF, and bFGF, than osteochondroma. Furthermore, the perichondral spindle cells and marrow osteoblasts/fibroblasts of BPOP showed stronger immunoreaction of PCNA, p53, β-catenin, BCL2, pAKT, survivin, 14-3-3, CEA, EMA, pan-K, and S-100 than the tumor cells of osteochondroma.

Conclusions

Therefore, it was presumed that similar to embryonal osteochondroid tissue, BPOP might be activated by osteogenic and oncogenic signaling and that this increased signaling may explain the rapid growth and high recurrence of BPOP.

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Radiobiologically based analysis of the influence of breathing motion and DIR method on lung treatment plans

Abstract

Objective

The purposes of this work are to investigate the influence of breathing motion on the quality of delivered radiation therapy treatment for lung cancer patients, to study the effect of tumor volume movement and anatomy change (due to the breathing motion) on the dose distribution through a radiobiological analysis, and finally, to examine the influence of the deformable image registration (DIR) method used on the 4D dose accumulation.

Methods

The work is based on the 4D CT image sets and treatment plans of ten lung cancer patients. For each patient, the actual delivered dose was approximated through the development of the "4D" treatment plan, which was created by applying the plan of the average intensity projection (AIP) CT on the ten respiratory phases of the 4D CT dataset. Additionally, the "4D optimal" plan was created, which was based on the optimized plans of each of the 4D CT phases using the same beam setup and objectives as for the 4D AIP plan. Equal weights were used for the different phases, and for both the 4D and 4D optimal cases, the individual phase plans were exported from the treatment planning system (TPS) to the Velocity AI where the dose distributions were summed using DIR together with the extended deformable multipass (EXDMP) and deformable multipass (DMP) methods. A radiobiological analysis was performed based on the radiobiological parameters of the involved organs at risk (OARs) and planning target volume (PTV).

Results

Using the complication-free tumor control probability (P ₊) index, non-negligible differences in P ₊ were observed between the 4D and 4D optimal dose distributions as well as between the dose distributions that were generated with different DIR methods. The optimal P ₊ values ranged from 9.4 to 98.8 % for the 4D case and from 17.1 to 99.1 % for the 4D optimal case. The clinical P ₊ values ranged from 4.3 to 81.4 % for the 4D case using the EXDMP method and from 4.3 to 81.5 % for the DMP method. These differences emphasize the significance of using the proper DIR algorithm and its influence on the final dose distribution.

Conclusion

The radiobiological and dosimetric analyses showed the importance of taking into account the breathing motion during treatment planning. That was especially evident for smaller tumors and tumors with large motion extent. Also, the importance of choosing the proper DIR method was found to be great since it may lead to large differences in the accumulated 4D dose distribution.

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Two randomized, double-blind, placebo-controlled, dose-escalation phase 1 studies evaluating BTH1677, a 1, 3–1,6 beta glucan pathogen associated molecular pattern, in healthy volunteer subjects

Summary

Background BTH1677 is a beta glucan pathogen associated molecular pattern (PAMP) currently being investigated as a novel cancer therapy. Here, the initial safety and pharmacokinetic (PK) results of BTH1677 in healthy subjects are reported. Subjects and Methods In the Phase 1a single-dosing study, subjects were randomized (3:1 per cohort) to a single intravenous (iv) infusion of BTH1677 at 0.5, 1, 2, 4, or 6 mg/kg or placebo, respectively. In the Phase 1b multi-dosing study, subjects were randomized (3:1 per cohort) to 7 daily iv infusions of BTH1677 at 1, 2, or 4 mg/kg or placebo, respectively. Safety and PK non-compartmental analyses were performed. Results Thirty-six subjects (N = 24 Phase 1a; N = 12 Phase 1b) were randomized to treatment. No deaths or serious adverse events occurred in either study. Mild or moderate adverse events (AEs) occurred in 67 % of BTH1677-treated subjects in both studies. Treatment-related AEs (occurring in ≥10 % of subjects) included dyspnea, flushing, headache, nausea, paraesthesia, and rash in Phase 1a and conjunctivitis and headache in Phase 1b. BTH1677 serum concentration was linear with dose. Clearance, serum elimination half-life (t_1/2) and volume of distribution (Vss) were BTH1677 dose-independent. In Phase 1b, area under the curve, t_1/2, and Vss values were larger at steady state on days 6–30 versus day 0. Conclusions BTH1677 was well tolerated after single doses up to 6 mg/kg and after 7 daily doses up to 4 mg/kg.

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UCA1 functions as a competing endogenous RNA to suppress epithelial ovarian cancer metastasis

Abstract

Urothelial cancer associated 1 (UCA1) is an example of functional long noncoding RNAs involved in many biologic processes. However, little is known about the association between UCA1 expression and metastasis in epithelial ovarian cancer (EOC). Findings of this study confirmed that not only UCA1 was aberrantly upregulated in EOC tissues and cells, but also correlated with status of lymph node metastasis and FIGO stage. Furthermore, univariate and multivariate analyses showed that UCA1 was a prognostic factor for overall survival in EOC patients. In vitro, knockdown of UCA1 reduced the invasion and migration ability of EOC cells. The results showed that UCA1 could function as an endogenous sponge by directly binding to miR-485-5p. Depletion of UCA1 was involved in the downregulation of matrix metallopeptidase 14 (MMP14) expression, a target gene of miR-485-5p. In conclusion, our work indicates that UCA1 is a new prognostic biomarker for EOC, establishing a novel connection among UCA1, miR-485-5p, and MMP14 in EOC metastasis.

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A truncated phosphorylated p130Cas substrate domain is sufficient to drive breast cancer growth and metastasis formation in vivo

Abstract

Elevated p130Cas (Crk-associated substrate) levels are found in aggressive breast tumors and are associated with poor prognosis and resistance to standard therapeutics in patients. p130Cas signals majorly through its phosphorylated substrate domain (SD) that contains 15 tyrosine motifs (YxxP) which recruit effector molecules. Tyrosine phosphorylation of p130Cas is important for mediating migration, invasion, tumor promotion, and metastasis. We previously developed a Src*/SD fusion molecule approach, where the SD is constitutively phosphorylated. In a polyoma middle T-antigen (PyMT)/Src*/SD double-transgenic mouse model, Src*/SD accelerates PyMT-induced tumor growth and promotes a more aggressive phenotype. To test whether Src*/SD also drives metastasis and which of the YxxP motifs are involved in this process, full-length and truncated SD molecules fused to Src* were expressed in breast cancer cells. The functionality of the Src*/SD fragments was analyzed in vitro, and the active proteins were tested in vivo in an orthotopic mouse model. Breast cancer cells expressing the full-length SD and the functional smaller SD fragment (spanning SD motifs 6–10) were injected into the mammary fat pads of mice. The tumor progression was monitored by bioluminescence imaging and caliper measurements. Compared with control animals, the complete SD promoted primary tumor growth and an earlier onset of metastases. Importantly, both the complete and truncated SD significantly increased the occurrence of metastases to multiple organs. These studies provide strong evidence that the phosphorylated p130Cas SD motifs 6–10 (Y236, Y249, Y267, Y287, and Y306) are important for driving mammary carcinoma progression.

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The MDM4 SNP34091 (rs4245739) C-allele is associated with increased risk of ovarian—but not endometrial cancer

Abstract

The MDM4 protein (also known as MDMX or HDMX) is a negative regulator of p53, not only by direct interaction but also through its interaction with MDM2. Further, MDM4 overexpression and amplification have been observed in several cancer forms. Recently, a single nucleotide polymorphism (SNP) in the 3' untranslated region of the MDM4 gene, SNP34091A > C (rs4245739) was reported to alter MDM4 messenger RNA (mRNA) stability by modulating a microRNA binding site, thereby leading to decreased MDM4 levels. In this case-control study, we aimed to evaluate the possible association between MDM4 SNP34091 status and cancer risk by comparing the genotype frequencies in large hospital-based cohorts of endometrial- (n = 1404) and ovarian (n = 1385) cancer patients with healthy female controls (n = 1870). Genotype frequencies were compared by odds ratio (OR) estimates and Fisher exact tests. We found that individuals harboring the MDM4 SNP34091AC/CC genotypes had a significantly elevated risk for serous ovarian cancer (SOC) in general and high-grade serous ovarian cancer (HGSOC) in particular (SOC: OR = 1.18., 95 % CI = 1.01–1.39; HGSOC: OR = 1.25, CI = 1.02–1.53). No association between SNP34091 genotypes and endometrial cancer risk was observed. Our data indicate the MDM4 SNP34091AC/CC genotypes to be associated with an elevated risk for SOC and in particular the HGSOC type.

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Association between the CpG island methylator phenotype and its prognostic significance in primary pulmonary adenocarcinoma

Abstract

Aberrant methylation of promoter CpG islands is one of the most important inactivation mechanisms for tumor suppressor and tumor-related genes. Previous studies using genome-wide DNA methylation microarray analysis have suggested the existence of a CpG island methylator phenotype (CIMP) in lung adenocarcinomas. Although the biological behavior of these tumors varies according to tumor stage, no large-scale study has examined the CIMP in lung adenocarcinoma patients according to tumor stage. Furthermore, there have been no reported results regarding the clinical significance of each of the six CIMP markers. To examine the CIMP in patients with pulmonary adenocarcinoma after a surgical resection, we performed methylation analysis of six genes (CCNA1, ACAN, GFRA1, EDARADD, MGC45800, and p16 ^INK4A) in 230 pulmonary adenocarcinoma cases using the SEQUENOM MassARRAY platform. Fifty-four patients (28 %, 54/191) were in the CIMP-high (CIMP-H) group associated with high nodal stage (P = 0.007), the presence of micropapillary or solid histology (P = 0.003), and the absence of an epidermal growth factor receptor (EGFR) mutation (P = 0.002). By multivariate analysis, CIMP was an independent prognostic marker for overall survival (OS) and disease-specific survival (P = 0.03 and P = 0.43, respectively). In the stage I subgroups alone, CIMP-H patients had lower OS rates than the CIMP-low (CIMP-L) group (P = 0.041). Of the six CIMP markers, ACAN alone was significantly associated with patient survival. CIMP predicted the risk of progression independently of clinicopathological variables and enables the stratification of pulmonary adenocarcinoma patients, particularly among stage I cases.

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Exosomal miRNAs as biomarkers of recurrent lung cancer

Abstract

Prognosis of lung cancer still remains grim largely due to recurrence and aggressive metastasis of the disease. In this study, we examined the potential of exosomal miRNAs as biomarkers of recurrent lung cancer. Initially, in vitro miRNA profiles of normal lung (Beas-2b) and lung cancer (H1299) cells and of exosomes isolated from conditioned media were determined. In vivo study involved establishing subcutaneous primary and recurrent lung cancer xenografts in nude mouse model and examining tumor and serum exosomal miRNA alteration in secondary/recurrent lung tumors. A total of 77 miRNAs were observed to be significantly modulated in the H1299 cells (47 miRNA upregulated and 30 downregulated) compared to the Beas-2b cells. The exosomes isolated from conditioned media indicated several miRNAs which were in agreement with cells of origin. A similarity was also observed between miRNAs from serum exosomes and tumors, indicating their origin from the lung tumors. Two miRNAs, miR-21 and miR-155, were found to be significantly upregulated in recurrent tumors compared to primary tumors. These miRNAs were also upregulated in serum exosomes of recurrent tumor-bearing animals versus non-tumor- or primary tumor-bearing animals. Increased expression of the recurrent disease markers were also observed in recurrent tumors compared with primary tumors. Serum exosomes from recurrent tumor mice mirrored its tumor profile in expressing higher levels of these proteins compared with exosomes from primary tumor mice. Our data suggest that exosomal miRNA signatures may be a true representation of a pathological profile of lung cancer; thus, miRNAs could serve as promising biomarkers for non-invasive diagnosis of the disease.

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Association between the CpG island methylator phenotype and its prognostic significance in primary pulmonary adenocarcinoma

Abstract

Aberrant methylation of promoter CpG islands is one of the most important inactivation mechanisms for tumor suppressor and tumor-related genes. Previous studies using genome-wide DNA methylation microarray analysis have suggested the existence of a CpG island methylator phenotype (CIMP) in lung adenocarcinomas. Although the biological behavior of these tumors varies according to tumor stage, no large-scale study has examined the CIMP in lung adenocarcinoma patients according to tumor stage. Furthermore, there have been no reported results regarding the clinical significance of each of the six CIMP markers. To examine the CIMP in patients with pulmonary adenocarcinoma after a surgical resection, we performed methylation analysis of six genes (CCNA1, ACAN, GFRA1, EDARADD, MGC45800, and p16 ^INK4A) in 230 pulmonary adenocarcinoma cases using the SEQUENOM MassARRAY platform. Fifty-four patients (28 %, 54/191) were in the CIMP-high (CIMP-H) group associated with high nodal stage (P = 0.007), the presence of micropapillary or solid histology (P = 0.003), and the absence of an epidermal growth factor receptor (EGFR) mutation (P = 0.002). By multivariate analysis, CIMP was an independent prognostic marker for overall survival (OS) and disease-specific survival (P = 0.03 and P = 0.43, respectively). In the stage I subgroups alone, CIMP-H patients had lower OS rates than the CIMP-low (CIMP-L) group (P = 0.041). Of the six CIMP markers, ACAN alone was significantly associated with patient survival. CIMP predicted the risk of progression independently of clinicopathological variables and enables the stratification of pulmonary adenocarcinoma patients, particularly among stage I cases.

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Exosomal miRNAs as biomarkers of recurrent lung cancer

Abstract

Prognosis of lung cancer still remains grim largely due to recurrence and aggressive metastasis of the disease. In this study, we examined the potential of exosomal miRNAs as biomarkers of recurrent lung cancer. Initially, in vitro miRNA profiles of normal lung (Beas-2b) and lung cancer (H1299) cells and of exosomes isolated from conditioned media were determined. In vivo study involved establishing subcutaneous primary and recurrent lung cancer xenografts in nude mouse model and examining tumor and serum exosomal miRNA alteration in secondary/recurrent lung tumors. A total of 77 miRNAs were observed to be significantly modulated in the H1299 cells (47 miRNA upregulated and 30 downregulated) compared to the Beas-2b cells. The exosomes isolated from conditioned media indicated several miRNAs which were in agreement with cells of origin. A similarity was also observed between miRNAs from serum exosomes and tumors, indicating their origin from the lung tumors. Two miRNAs, miR-21 and miR-155, were found to be significantly upregulated in recurrent tumors compared to primary tumors. These miRNAs were also upregulated in serum exosomes of recurrent tumor-bearing animals versus non-tumor- or primary tumor-bearing animals. Increased expression of the recurrent disease markers were also observed in recurrent tumors compared with primary tumors. Serum exosomes from recurrent tumor mice mirrored its tumor profile in expressing higher levels of these proteins compared with exosomes from primary tumor mice. Our data suggest that exosomal miRNA signatures may be a true representation of a pathological profile of lung cancer; thus, miRNAs could serve as promising biomarkers for non-invasive diagnosis of the disease.

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Enzymatically active cathepsin D sensitizes breast carcinoma cells to TRAIL

Abstract

Cathepsin D (CD), a ubiquitously expressed lysosomal aspartic protease, is upregulated in human breast carcinoma and many other tumor types. CD has been repeatedly reported to act as key mediator of apoptosis induced by various chemotherapeutics. However, there is still controversy over the role of enzymatic/proteolytic versus protein-protein interaction activities of CD in apoptotic signaling. The elucidation of molecular mechanism responsible for the effect of CD in the chemotherapy-induced cell death is crucial for development of an appropriate strategy to target this protease in cancer treatment. Therefore, the objective of this study was to investigate the molecular mechanism behind the CD-mediated regulation of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced cell death. For this purpose, MDA-MB-231 breast carcinoma cells with an increased level of wt CD (CD) or mutant enzymatically inactive CD (ΔCD) were subjected to TRAIL and the frequency of apoptosis was determined. Our results show that CD facilitates the TRAIL-induced apoptosis of MDA-MB-231 breast cancer cells in enzymatic activity-dependent manner. Moreover, the importance of endosomal/lysosomal acidification in this process was documented. Analysis of the potential substrates specifically cleaved by CD during the TRAIL-induced apoptosis confirmed caspase-8 and Bid proteins as the CD targets. Moreover, in search for protein regulators of apoptosis that can be cleaved by CD at physiologically relevant pH, we identified the Bcl-2 protein as a suitable candidate. The modulatory role of CD in cell response to TRAIL was also confirmed in another breast cancer cell line SKBR3. These experiments identified the CD enzymatic activity as a new factor affecting sensitivity of breast cancer cells to TRAIL.

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Oxytocin as a protective agent in cisplatin-induced ototoxicity

Abstract

Purpose

Cisplatin is a potent chemotherapeutic drug with serious side effects such as ototoxicity which is characterized by irreversible, bilateral, progressive sensorineural hearing loss. Oxytocin, which is a well-known hormone secreting during pregnancy, has antioxidant and antiinflammatory effect. Our study aims to test and compare the effect of intratympanic (IT) and intraperitoneal (IP) oxytocin on cisplatin ototoxicity with DPOAE.

Methods

A total of 24 Wistar albino rats were randomly divided into four groups: Group 1 received 0.1–0.3 ml IT saline + IP saline solutions for 4 days (n = 6), Group 2 received cumulative dose of 20 mg/kg IP cisplatin divided into two equal doses in first and second days of experiment + 0.1–0.3 ml IT saline for 4 days, Group 3 received same dose of cisplatin as Group 2 + 0.1–0.3 ml IT oxytocin for 4 days, and Group 4 received same dose of cisplatin as Groups 2 and 3 + IP oxytocin with dose of 1 mg/kg. DPOAE was performed prior to procedure and at the end of the experiment on day 5.

Results

Group 2 showed severe ototoxic effect of cisplatin according to DPOAE result (p < 0.05). When compared with Group 2, DPOAE amplitude reductions were smaller in Group 3 (3.2, 3.8, 4.5, 6.3 and 7.6 kHz) (p < 0.05) and Group 4 which is statistically significant in 5.4, 6.3 and 7.6 kHz (p < 0.05). When Group 3 and Group 4 were compared, reductions were smaller in 2.7 and 3.2 kHz in Group 3 (p < 0.05).

Conclusion

In this study, we showed the protective effect of IT and IP oxytocin on cisplatin ototoxicity. We suggest oxytocin in cisplatin ototoxicity, especially via IT route even with high-dose cisplatin.

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Health Services Research and Regionalization of Care—From Policy to Practice: the Ontario Experience in Head and Neck Cancer

Abstract

Patients being treated at higher case volume hospitals or by higher case volume physicians appear to have better outcomes. This volume–outcome relationship is reviewed for oncologic and non-oncologic surgery with a focus on head and neck oncology. The impact of these research findings on health policy and health-care organization in Ontario, Canada, is then outlined. Lastly, future directions for quality improvement in surgical oncology are reviewed in the context of a universal health-care system. These include surgeon report cards, pre-operative checklists, linking funding and remuneration to the quality of delivered care, and the use of process improvement techniques.

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Comparable senescence induction in 3D human cartilage model by exposure to therapeutic doses of X-rays or C-ions

Publication date: Available online 11 February 2016
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Dounia Houria Hamdi, François Chevalier, Jean-Emmanuel Groetz, Florent Durantel, Jean-Yves Thuret, Carl Mann, Yannick Saintigny
PurposeParticle therapy using carbon ions (C-ions) has been successfully used in the treatment of tumors resistant to conventional radiation-therapy. However, the potential side effects to healthy cartilage exposed to lower linear energy transfer (LET) ions in the beam track prior the tumor, have not been evaluated. The aim of this study was to assess the extent of damage following C-ions irradiation in a 3D cartilage model close to human homeostasis.Methods and MaterialsPrimary human articular chondrocytes from a healthy donor were cultured in a collagen scaffold to construct a physioxic 3D cartilage model. Monolayer 2D culture was used as a reference. Cells were irradiated with a single dose of monoenergetic C-ions beam with a linear energy transfer of approximatively 30 keV/μm. This LET corresponds to the entrance channel of C-ions in the shallow healthy tissues before the spread-out Bragg peak (∼100 keV/μm) during hadrontherapy protocols. The same dose of X-rays was used as a reference. Survival, cell death and senescence assays were performed.ResultsAs expected, in 2D culture, C-ions were more efficient than X-rays in reducing cell survival with a relative biological effectiveness of 2.6. This was correlated with a stronger radiation-induced senescence (two-fold) but not to higher cell death induction. Interestingly, this differential effect was not reflected in 3D. Indeed, both ionizing radiations induced comparable rate of senescence induction in 3D.ConclusionsThe higher biological effectiveness of C-ions compared to low-LET radiations taken into account in treatment planning systems might be misevaluated using 2D culture experiments. Radiation-induced senescence is an important factor of potential cartilage attrition. The present data should encourage the scientific community to use relevant models and beams to improve the use of charged particles with a better safety for patients.

Teaser

The relative biological effectiveness of carbon ions compared to X-rays scored 2.6 in primary human articular chondrocytes cultured in 2D. This was correlated to a stronger cellular senescence induction (two-fold). This differential effect was not reflected in 3D cartilage model as both ionizing radiations induced comparable senescence. Carbon ions seem as safe as X-rays to articular cartilage in the context of radiation-therapy.


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Evaluation of robustness to setup and range uncertainties for head and neck patients treated with pencil beam scanning proton therapy

Publication date: Available online 11 February 2016
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Robert Malyapa, Matthew Lowe, Alessandra Bolsi, Antony J. Lomax, Damien C. Weber, Francesca Albertini
PurposeTo evaluate the robustness of head and neck (H&N) plans, treated using intensity modulated proton therapy (IMPT), to range and setup errors and to establish robustness parameters for the planning of future H&N treatments.Methods and MaterialsTen patients previously treated at XXXX were evaluated in terms of robustness to range and setup errors. Error bar dose distributions were generated for each plan, from which a number of metrics were extracted and used to define a 'robustness database' of acceptable parameters over all analysed plans. Patients were treated in sequentially delivered series and plans evaluated for both the first series and for the combined error over the whole treatment. To demonstrate the application of such a database in the head and neck, for one patient, an alternative treatment plan was generated using a simultaneous integrated boost (SIB) approach, as well as plans of differing numbers of fields.ResultsThe 'robustness database' for the treatment of H&N patients is presented. In an example case, comparison of single and multiple field plans against the database show clear improvements in robustness by using multiple fields. Comparing sequentially delivered series and a simultaneous integrated boost approach for this patient show both to be of comparable robustness, although the SIB approach shows a slightly greater sensitivity to uncertaintiesConclusionsA 'robustness database' has been created for the treatment of H&N patients with IMPT based on previous clinical experience. This will allow for the identification of future plans which may benefit from alternative planning approaches to improve robustness

Teaser

Proton plans can be sensitive to errors such as arise from range and setup uncertainties. The robustness of 10 head and neck patients to these uncertainties was evaluated and a database summarising robustness metrics based on these plans was generated which can be used to guide the planning of such treatments. The application of this database was demonstrated by comparing different planning techniques and evaluating the effect of using a different number of fields.


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Can Surface Imaging improve the Patient Set-up for Proton Post-Mastectomy Chestwall Irradiation?

Publication date: Available online 11 February 2016
Source:Practical Radiation Oncology
Author(s): Estelle Batin, Nicolas Depauw, Shannon MacDonald, Hsiao-Ming Lu




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How breast cancer chemotherapy increases the risk of leukaemia: Thoughts about a case of diffuse large B-cell lymphoma and leukaemia after breast cancer chemotherapy.

How breast cancer chemotherapy increases the risk of leukaemia: Thoughts about a case of diffuse large B-cell lymphoma and leukaemia after breast cancer chemotherapy.

Cancer Biol Ther. 2016 Feb 9;:0

Authors: Zhang B, Zhang X, Li M, Kong L, Deng X, Yu J

Abstract
The latest studies suggest that prophylactic chemotherapy or adjuvant chemotherapy for early stage breast cancer may increase the leukaemia risk in patients. For patients with a low risk for breast cancer recurrence, physicians who make the choice for adjuvant therapy should consider the risk of its long-term side effects. Is the occurrence of lymphatic system cancer and leukaemia after breast cancer treatment associated with chemotherapy? Can these types of leukaemia be classified as therapy-related leukaemias? We believe that there may be correlations between any diseases, butwe cannot rush to conclusions or dismiss a correlation because we understand little about the diseases themselves.In this paper, we present a case of secondary diffuse large B-cell lymphoma and leukaemia in patients after breast cancer chemotherapy, it is undeniable that this is a special event. For two distinct tumouroccurrences at different times, we cannot give a clear explanation because of thechanges in the genes that might link them together. and we hope to attract the attention of otherclinicians.

PMID: 26861804 [PubMed - as supplied by publisher]

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Health behaviours and fear of cancer recurrence in 10 969 colorectal cancer (CRC) patients

Abstract

Background

This study aimed to examine whether fear of cancer recurrence (FCR) was related to two important health behaviours (physical activity and smoking) in a large sample of colorectal cancer patients.

Methods

Ten thousand nine hundred sixty nine patients, diagnosed in 2010–11, and in remission in 2013, completed the 'Living with and Beyond Colorectal Cancer' survey. The survey included purpose-designed questions on fear of recurrence ('I have fear about my cancer coming back'), demographics, treatment and health variables. Physical activity (PA) was recorded as number of days per week doing at least 30 min of brisk activity, and smoking status was reported.

Results

Fifty per cent of respondents reported fear of their cancer returning. More women than men ((Odds Ratio; (OR) 1.58; 95% confidence interval (CI) 1.46, 1.71)) more younger than older patients (OR 2.53; CI 2.33, 2.74) and slightly more patients from deprived areas (OR 1.14, 1.05, 1.23) reported FCR. Independently of demographics and treatment, compared with those meeting the PA guidelines, those who were doing only 'some' (OR 1.22; CI 1.11, 1.35) or 'no' PA (OR 1.28; CI 1.15, 1.42) reported higher FCR. Compared with non-smokers, more current smokers reported fear (OR 1.34, CI 1.10, 1.58) and slightly more ex-smokers (OR 1.11; CI 1.04, 1.21).

Conclusions

This cross-sectional study provided novel data showing that colorectal cancer survivors with poorer health behaviours (those with lower activity levels and those who smoked) were more likely to experience FCR. Future research should replicate findings using detailed measures of fear, objective measures of health behaviours and identify directions of associations. © 2016 The Authors. Psycho-Oncology Published by John Wiley & Sons Ltd.

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Impact of gender on decisions to participate in faecal immunochemical test-based colorectal cancer screening: a qualitative study

Abstract

Objective

Faecal immunochemical tests (FITs) are increasingly being used in population-based colorectal cancer-screening programmes. Uptake of FIT is lower in men than women; however, the reasons for this are not well understood. We aimed to explore gender differences in influences on decisions to participate in FIT screening.

Methods

This is a qualitative study using in-depth face-to-face interviews of four groups of screening invitees (male and female screening users and male and female screening non-users), purposively sampled from the database of a population-based FIT screening programme. Recruitment continued until saturation was reached. Interviews were audio recorded and transcribed verbatim. Thematic analysis using the framework approach was employed with the theoretical domains framework guiding analysis.

Results

Forty-seven screening invitees were interviewed. Six theoretical domains influenced screening uptake: 'environmental context and resources', 'beliefs about capabilities', 'beliefs about consequences', 'emotions', 'social influences' and 'knowledge'. Male non-users were often fatalistic, less knowledgeable and misinformed about cancer and FIT screening compared with other groups. Female non-users expressed negative attitudes, beliefs and emotions towards FIT screening, cancer, social influences and the medical profession and were over-confident about their health.

Conclusions

Negative attitudes and emotions to screening dominated non-user decision-making but differed by gender. Opportunities to improve uptake in men and women exist. Greater national discussions on the benefits of FIT screening, and development of screening materials tackling negative attitudes and beliefs while recognising male/female differences, may improve screening uptake. Copyright © 2016 John Wiley & Sons, Ltd.

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How breast cancer chemotherapy increases the risk of leukaemia: Thoughts about a case of diffuse large B-cell lymphoma and leukaemia after breast cancer chemotherapy.

How breast cancer chemotherapy increases the risk of leukaemia: Thoughts about a case of diffuse large B-cell lymphoma and leukaemia after breast cancer chemotherapy.

Cancer Biol Ther. 2016 Feb 9;:0

Authors: Zhang B, Zhang X, Li M, Kong L, Deng X, Yu J

Abstract
The latest studies suggest that prophylactic chemotherapy or adjuvant chemotherapy for early stage breast cancer may increase the leukaemia risk in patients. For patients with a low risk for breast cancer recurrence, physicians who make the choice for adjuvant therapy should consider the risk of its long-term side effects. Is the occurrence of lymphatic system cancer and leukaemia after breast cancer treatment associated with chemotherapy? Can these types of leukaemia be classified as therapy-related leukaemias? We believe that there may be correlations between any diseases, butwe cannot rush to conclusions or dismiss a correlation because we understand little about the diseases themselves.In this paper, we present a case of secondary diffuse large B-cell lymphoma and leukaemia in patients after breast cancer chemotherapy, it is undeniable that this is a special event. For two distinct tumouroccurrences at different times, we cannot give a clear explanation because of thechanges in the genes that might link them together. and we hope to attract the attention of otherclinicians.

PMID: 26861804 [PubMed - as supplied by publisher]

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Effects of methylglyoxal and glyoxalase I inhibition on breast Cancer cells proliferation, invasion, and apoptosis through modulation of MAPKs, MMP9, and Bcl-2

10.1080/15384047.2015.1121346<br/>Yi Guo

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Resection of colorectal liver metastases in the elderly—Is it justified?

Background and Objectives

Liver resection of colorectal liver metastasis (CRLM) may necessitate large metabolic and physiologic reserve. As the population ages, resection of CRLM is increasingly required in the elderly. We assessed the safety and efficacy of these operations.

Methods

Between February 2010 and 2015, 174 patients underwent liver resection of CRLM. Fifty-four and 120 patients were over and under the age of 70 at the time of surgery, respectively (mean ages: 76 ± 4 and 56.5 ± 9 years). Patient and tumor characteristics, perioperative, and long-term outcomes were compared.

Results

Elderly patients had increased rates of IHD (18.5% versus 6.6%, P = 0.0002), COPD (9.2% versus 4.1%, P = 0.01), and DM (30% versus 14%, P = 0.02). Operative time was shorter in elderly patients (222 ± 109 versus 261 ± 110 min; P = 0.04). Intraoperative blood loss was comparable. The rate of minor postoperative complications was similar between groups, but elderly patients had higher rate of major complications (11.1% versus 2.5%, P < 0.0001). One elderly patient died following surgery (1.8%). Length of hospital stay was similar between groups. No difference in 3-year survival was demonstrated.

Conclusions

Although associated with a small increase in postoperative morbidity and mortality, liver resection may be performed safely and effectively in carefully selected elderly patients. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.

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