Category: Oncology

Hot Topics: Financial Concerns Hinder Younger Cancer Survivors’ Treatment Compliance

Do cancer survivors change their prescription drug use for financial reasons? Findings from a nationally representative sample in the United States

Zheng Z, Han X, Guy GP, et al. Do cancer survivors change their prescription drug use for financial reasons? Findings from a nationally representative sample in the United States. Cancer. 2017:n/a-n/a. http://dx.doi.org/10.1002/cncr.30560.

BACKGROUND
There is limited evidence from nationally representative samples about changes in prescription drug use for financial reasons among cancer survivors in the United States.
METHODS
The 2011 to 2014 National Health Interview Survey was used to identify adults who reported ever having been told they had cancer (cancer survivors; n = 8931) and individuals without a cancer history (n = 126,287). Measures of changes in prescription drug use for financial reasons included: 1) skipping medication doses, 2) taking less medicine, 3) delaying filling a prescription, 4) asking a doctor for lower cost medication, 5) buying prescription drugs from another country, and 6) using alternative therapies. Multivariable logistic regression analyses were controlled for demographic characteristics, number of comorbid conditions, interactions between cancer history and number of comorbid conditions, and health insurance coverage. Main analyses were stratified by age (nonelderly, ages 18-64 years; elderly, ages ≥65 years) and time since diagnosis (recently diagnosed, <2 years; previously diagnosed, ≥2 years).
RESULTS
Among nonelderly individuals, both recently diagnosed (31.6%) and previously diagnosed (27.9%) cancer survivors were more likely to report any change in prescription drug use for financial reasons than those without a cancer history (21.4%), with the excess percentage changes for individual measures ranging from 3.5% to 9.9% among previously diagnosed survivors and from 2.6% to 2.7% among recently diagnosed survivors (P < .01). Elderly cancer survivors and those without a cancer history had comparable rates of changes in prescription drug use for financial reasons.
CONCLUSIONS
Nonelderly cancer survivors are particularly vulnerable to changes in prescription drug use for financial reasons, suggesting that targeted efforts are needed. Cancer 2017. © 2017 American Cancer Society.
Posted in Hot Topics in Research, Oncology

Hot Topics: Larger Racial Disparity in Cervical Cancer Gap Than Previously Estimated

Hysterectomy-corrected cervical cancer mortality rates reveal a larger racial disparity in the United States

Beavis AL, Gravitt PE, Rositch AF. Hysterectomy-corrected cervical cancer mortality rates reveal a larger racial disparity in the United States. Cancer. 2017. http://dx.doi.org/10.1002/cncr.30507.

BACKGROUND
The objectives of this study were to determine the age-standardized and age-specific annual US cervical cancer mortality rates after correction for the prevalence of hysterectomy and to evaluate disparities by age and race.

METHODS
Estimates for deaths due to cervical cancer stratified by age, state, year, and race were derived from the National Center for Health Statistics county mortality data (2000-2012). Equivalently stratified data on the prevalence of hysterectomy for women 20 years old or older from the Behavioral Risk Factor Surveillance System survey were used to remove women who were not at risk from the denominator. Age-specific and age-standardized mortality rates were computed, and trends in mortality rates were analyzed with Joinpoint regression.

RESULTS
Age-standardized rates were higher for both races after correction. For black women, the corrected mortality rate was 10.1 per 100,000 (95% confidence interval [CI], 9.6-10.6), whereas the uncorrected rate was 5.7 per 100,000 (95% CI, 5.5-6.0). The corrected rate for white women was 4.7 per 100,000 (95% CI, 4.6-4.8), whereas the uncorrected rate was 3.2 per 100,000 (95% CI, 3.1-3.2). Without the correction, the disparity in mortality between races was underestimated by 44%. Black women who were 85 years old or older had the highest corrected rate: 37.2 deaths per 100,000. A trend analysis of corrected rates demonstrated that white women’s rates decreased at 0.8% per year, whereas the annual decrease for black women was 3.6% (P < .05).

CONCLUSIONS
A correction for hysterectomy has revealed that cervical cancer mortality rates are underestimated, particularly in black women. The highest rates are seen in the oldest black women, and public health efforts should focus on appropriate screening and adequate treatment in this population. Cancer 2017. © 2017 American Cancer Society.

Posted in Front Page, Hot Topics in Research, Oncology

Hot Topics: New Free Database Crowdsources Cancer Mutation Research

CIViC is a Community Knowledgebase for Expert Crowdsourcing the Clinical Interpretation of Variants in Cancer

Griffith M, Spies NC, Krysiak K, et al. CIViC is a community knowledgebase for expert crowdsourcing the clinical interpretation of variants in cancer. Nat Genet. 2017;49(2):170-174. http://dx.doi.org/10.1038/ng.3774.

CIViC is an expert-crowdsourced knowledgebase for Clinical Interpretation of Variants in Cancer describing the therapeutic, prognostic, diagnostic and predisposing relevance of inherited and somatic variants of all types. CIViC is committed to open-source code, open-access content, public application programming interfaces (APIs) and provenance of supporting evidence to allow for the transparent creation of current and accurate variant interpretations for use in cancer precision medicine.

Posted in Front Page, Hot Topics in Research, Oncology

A Souvenir Smuggled Home From Cuba: A Cancer Vaccine

A Souvenir Smuggled Home From Cuba: A Cancer Vaccine

Lung cancer patients are travelling to Cuba.

 

Posted in December, Hot Topics in Research, Lung, News, Oncology

Sexual Health in Women Affected by Cancer: Focus on Sexual Pain

Sexual Health in Women Affected by Cancer: Focus on Sexual Pain

As cancer therapies improve, the number of women surviving or living long lives with cancer continues to increase. Treatment modalities, including surgery, chemotherapy, radiotherapy, and hormonal therapy, affect sexual function and may cause sexual pain through a variety of mechanisms, depending on treatment type. Adverse sexual effects resulting from ovarian damage, anatomic alterations, and neurologic, myofascial, or pelvic organ injury may affect more than half of women affected by cancer. Despite the fact that no specialty is better qualified to render care for this consequence of cancer treatments, many obstetrician–gynecologists (ob-gyns) feel uncomfortable or ill-equipped to address sexual pain in women affected by cancer. Asking about sexual pain and dyspareunia and performing a thorough physical examination are essential steps to guide management, which must be tailored to individual patient goals. Understanding the cancer treatment-related pathophysiology of sexual pain aids in providing this care. Effective mechanism-based treatments for sexual pain and dyspareunia are available, and by using them, knowledgeable ob-gyns can enhance the quality of life of potentially millions of women affected by cancer.

 

Deborah Coady, MD, and Vanessa Kennedy, MD

Obstet Gynecol 2016;128:775–91    DOI: 10.1097/AOG.0000000000001621

Posted in December, Hot Topics in Research, Oncology

Long-term benefits and risks of frontline nilotinib vs imatinib for chronic myeloid leukemia in chronic phase: 5-year update of the randomized ENESTnd trial

Long-term benefits and risks of frontline nilotinib vs imatinib for chronic myeloid leukemia in chronic phase: 5-year update of the randomized ENESTnd trial

In the phase 3 Evaluating Nilotinib Efficacy and Safety in Clinical Trials–Newly Diagnosed Patients (ENESTnd) study, nilotinib resulted in earlier and higher response rates and a lower risk of progression to accelerated phase/blast crisis (AP/BC) than imatinib in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP). Here, patients’ long-term outcomes in ENESTnd are evaluated after a minimum follow-up of 5 years. By 5 years, more than half of all patients in each nilotinib arm (300 mg twice daily, 54%; 400 mg twice daily, 52%) achieved a molecular response 4.5 (MR4.5; BCR-ABL ⩽0.0032% on the International Scale) compared with 31% of patients in the imatinib arm. A benefit of nilotinib was observed across all Sokal risk groups. Overall, safety results remained consistent with those from previous reports. Numerically more cardiovascular events (CVEs) occurred in patients receiving nilotinib vs imatinib, and elevations in blood cholesterol and glucose levels were also more frequent with nilotinib. In contrast to the high mortality rate associated with CML progression, few deaths in any arm were associated with CVEs, infections or pulmonary diseases. These long-term results support the positive benefit-risk profile of frontline nilotinib 300 mg twice daily in patients with CML-CP.

A Hochhaus, G Saglio, TP Hughes, RA Larson, D-W Kim, S Issaragrisil, PD le Coutre, G Etienne , PE Dorlhiac-Llacer, RE Clark, IW Flinn, H Nakamae, B Donohue, W Deng, D Dalal, HD Menssen and HM Kantarjian

Leukemia (2016) 30, 1044–1054; doi:10.1038/leu.2016.5

Posted in August, Blood, Hot Topics in Research, Oncology

Association Between Treatment at a High-Volume Facility and Improved Survival for Radiation-Treated Men With High-Risk Prostate Cancer

Association Between Treatment at a High-Volume Facility and Improved Survival for Radiation-Treated Men With High-Risk Prostate Cancer

Purpose: Although the association between higher hospital volume and improved outcomes has been well-documented in surgery, there is little data about whether this effect exists for radiation-treated patients. We investigated whether treatment at a radiation facility that treats a high volume of prostate cancer patients is associated with improved survival for men with high-risk prostate cancer. Methods and Materials: We used the National Cancer Database (NCDB) to identity patients diagnosed with prostate cancer from 2004 to 2006. The radiation case volume (RCV) of each hospital was based on its number of radiation-treated prostate cancer patients. We used propensity-score based analysis to compare the overall survival (OS) of high-risk prostate cancer patients in high versus low RCV hospitals. Primary endpoint is overall survival. Covariates adjusted for were tumor characteristics, sociodemographic factors, radiation type, and use of androgen deprivation therapy (ADT). Results: A total of 19,565 radiation-treated high-risk patients were identified. Median follow-up was 81.0 months (range: 1-108 months). When RCV was coded as a continuous variable, each increment of 100 radiation-managed patients was associated with improved OS (adjusted hazard ratio [AHR]: 0.97; 95% confidence interval [CI]: 0.95- 0.98; P<.0001) after adjusting for known confounders. For illustrative purposes, when RCV was dichotomized at the 80th percentile (43 patients/year), high RCV was associated with improved OS (7-year overall survival 76% vs 74%, log-rank test PZ.0005; AHR: 0.91, 95% CI: 0.86-0.96, PZ.0005). This association remained significant when RCV was dichotomized at 75th (37 patients/year), 90th (60 patients/year), and 95th (84 patients/year) percentiles but not the 50th (19 patients/year). Conclusions: Our results suggest that treatment at centers with higher prostate cancer radiation case volume is associated with improved OS for radiation-treated men with high-risk prostate cancer. 

Int J Radiation Oncol Biol Phys, Vol. 94, No. 4, pp. 683e690, 2016

Copyright: 2016 The Authors

Yu-Wei Chen, MD, MS, Brandon A. Mahal, MD, Vinayak Muralidhar, MSc, Michelle Nezolosky, BA, Clair J. Beard, MD, Robert B. Den, MD, Felix Y. Feng, MD,Karen E. Hoffman, MD, MPH, MHSc, Neil E. Martin, MD, MPH, Peter F. Orio, DO, MS, and Paul L. Nguyen, MD

Posted in April, Hot Topics in Research, Oncology, Prostate Tagged with: ,

Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report

Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report

BACKGROUND: We update recommendations on 12 topics that were in the 9th edition of these guidelines, and address 3 new topics.

METHODS: We generate strong (Grade 1) and weak (Grade 2) recommendations based on high- (Grade A), moderate- (Grade B), and low- (Grade C) quality evidence.

RESULTS: For VTE and no cancer, as long-term anticoagulant therapy, we suggest dabigatran (Grade 2B), rivaroxaban (Grade 2B), apixaban (Grade 2B), or edoxaban (Grade 2B) over vitamin K antagonist (VKA) therapy, and suggest VKA therapy over low-molecular-weight heparin (LMWH; Grade 2C). For VTE and cancer, we suggest LMWH over VKA (Grade 2B), dabigatran (Grade 2C), rivaroxaban (Grade 2C), apixaban (Grade 2C), or edoxaban (Grade 2C). We have not changed recommendations for who should stop anticoagulation at 3 months or receive extended therapy. For VTE treated with anticoagulants, we recommend against an inferior vena cava filter (Grade 1B). For DVT, we suggest not using compression stockings routinely to prevent PTS (Grade 2B). For subsegmental pulmonary embolism and no proximal DVT, we suggest clinical surveillance over anticoagulation with a low risk of recurrent VTE (Grade 2C), and anticoagulation over clinical surveillance with a high risk (Grade 2C). We suggest thrombolytic therapy for pulmonary embolism with hypotension (Grade 2B), and systemic therapy over catheter-directed thrombolysis (Grade 2C). For recurrent VTE on a non-LMWH anticoagulant, we suggest LMWH (Grade 2C); for recurrent VTE on LMWH, we suggest increasing the LMWH dose (Grade 2C).

CONCLUSIONS: Of 54 recommendations included in the 30 statements, 20 were strong and none was based on high-quality evidence, highlighting the need for further research.

 

CHEST 2016; 149(2):315-352

Clive Kearon, MD, PhD; Elie A. Akl, MD, MPH, PhD; Joseph Ornelas, PhD; Allen Blaivas, DO, FCCP; David Jimenez, MD, PhD, FCCP; Henri Bounameaux, MD; Menno Huisman, MD, PhD; Christopher S. King, MD, FCCP; Timothy A. Morris, MD, FCCP; Namita Sood, MD, FCCP; Scott M. Stevens, MD; Janine R. E. Vintch, MD, FCCP; Philip Wells, MD; Scott C. Woller, MD; and COL Lisa Moores, MD, FCCP

Posted in Blood, Hot Topics in Research, Lung, March, Research Commentary

Long-term toxic effects of proton radiotherapy for paediatric medulloblastoma: a phase 2 single-arm study

Long-term toxic effects of proton radiotherapy for paediatric medulloblastoma: a phase 2 single-arm study

Background

Compared with traditional photon radiotherapy, proton radiotherapy irradiates less normal tissue and might improve health outcomes associated with photon radiotherapy by reducing toxic effects to normal tissue. We did a trial to assess late complications, acute side-effects, and survival associated with proton radiotherapy in children with medulloblastoma.

Methods

In this non-randomised, open-label, single-centre, phase 2 trial, we enrolled patients aged 3–21 years who had medulloblastoma. Patients had craniospinal irradiation of 18–36 Gy radiobiological equivalents (GyRBE) delivered at 1·8 GyRBE per fraction followed by a boost dose. The primary outcome was cumulative incidence of ototoxicity at 3 years, graded with the Pediatric Oncology Group ototoxicity scale (0–4), in the intention-to-treat population. Secondary outcomes were neuroendocrine toxic effects and neurocognitive toxic effects, assessed by intention-to-treat. This study is registered at ClinicalTrials.gov, number NCT00105560.

Findings

We enrolled 59 patients from May 20, 2003, to Dec 10, 2009: 39 with standard-risk disease, six with intermediate-risk disease, and 14 with high-risk disease. 59 patients received chemotherapy. Median follow-up of survivors was 7·0 years (IQR 5·2–8·6). All patients received the intended doses of proton radiotherapy. The median craniospinal irradiation dose was 23·4 GyRBE (IQR 23·4–27·0) and median boost dose was 54·0 GyRBE (IQR 54·0–54·0). Four (9%) of 45 evaluable patients had grade 3–4 ototoxicity according to Pediatric Oncology Group ototoxicity scale in both ears at follow-up, and three (7%) of 45 patients developed grade 3–4 ototoxicity in one ear, although one later reverted to grade 2. The cumulative incidence of grade 3–4 hearing loss at 3 years was 12% (95% CI 4–25). At 5 years, it was 16% (95% CI 6–29). Pediatric Oncology Group hearing ototoxicity score at a follow-up of 5·0 years (IQR 2·9–6·4) was the same as at baseline or improved by 1 point in 34 (35%) of 98 ears, worsened by 1 point in 21 (21%), worsened by 2 points in 35 (36%), worsened by 3 points in six (6%), and worsened by 4 points in two (2%). Full Scale Intelligence Quotient decreased by 1·5 points (95% CI 0·9–2·1) per year after median follow-up up of 5·2 years (IQR 2·6–6·4), driven by decrements in processing speed and verbal comprehension index. Perceptual reasoning index and working memory did not change significantly. Cumulative incidence of any neuroendocrine deficit at 5 years was 55% (95% CI 41–67), with growth hormone deficit being most common. We recorded no cardiac, pulmonary, or gastrointestinal late toxic effects. 3-year progression-free survival was 83% (95% CI 71–90) for all patients. In post-hoc analyses, 5-year progression-free survival was 80% (95% CI 67–88) and 5-year overall survival was 83% (95% CI 70–90).

Interpretation

Proton radiotherapy resulted in acceptable toxicity and had similar survival outcomes to those noted with conventional radiotherapy, suggesting that the use of the treatment may be an alternative to photon-based treatments.

Torunn I Yock, Beow Y Yeap, David H Ebb, Elizabeth Weyman, Bree R Eaton, Nicole A Sherry, Robin M Jones, Shannon M MacDonald, Margaret B Pulsifer, Beverly Lavally, Annah N Abrams, Mary S Huang, Karen J Marcus, Nancy J Tarbell

The Lancet Oncology

Posted in Brain, February, Hot Topics in Research, Oncology, Pediatrics Tagged with: , ,

Prostate cancer discovery may make it easier to kill cancer cells

Checkpoint Kinase 2 Negatively Regulates Androgen Sensitivity and Prostate Cancer Cell Growth

Abstract:

Prostate cancer is the second leading cause of cancer death in American men, and curing metastatic disease remains a significant challenge. Nearly all patients with disseminated prostate cancer initially respond to androgen deprivation therapy (ADT), but virtually all patients will relapse and develop incurable castrationresistant prostate cancer (CRPC). A high-throughput RNAi screen to identify signaling pathways regulating prostate cancer cell growth led to our discovery that checkpoint kinase 2 (CHK2) knockdown dramatically increased prostate cancer growth and hypersensitized cells to low androgen levels. Mechanistic investigations revealed that the effects of CHK2 were dependent on the downstream signaling proteins CDC25C and CDK1. Moreover, CHK2depletion increased androgen receptor (AR) transcriptional activity on androgen-regulated genes, substantiating the finding that CHK2 affects prostate cancer proliferation, partly, through the AR. Remarkably, we further show that CHK2 is a novel ARrepressed gene, suggestive of a negative feedback loop between CHK2 and AR. In addition, we provide evidence that CHK2 physically associates with the AR and that cell-cycle inhibition increased this association. Finally, IHC analysis of CHK2 in prostate cancer patient samples demonstrated a decrease in CHK2 expression in high-grade tumors. In conclusion, we propose that CHK2 is a negative regulator of androgen sensitivity and prostate cancer growth, and that CHK2 signaling is lost during prostate cancer progression to castration resistance. Thus, perturbing CHK2 signaling may offer a new therapeutic approach for sensitizing CRPC to ADT and radiation.

 

Cancer Research. 12/1/2015, Vol. 75 Issue 23, p5093-5105. 13p.

Posted in Hot Topics in Research, Oncology, Prostate, Uncategorized