Role of endolaryngeal surgery (with or without laser) compared with radiotherapy in the management of early (T1) glottic cancer: a clinical practice guideline

Aims

To provide evidence-based practice guideline recommendations concerning the role of endolaryngeal surgery (with or without laser) compared with radiation therapy for patients with early (T1) glottic cancer, assessing survival, locoregional control, laryngeal preservation rates, and voice outcomes.

Methods

The medline, embase, and Cochrane Library databases were searched to identify relevant studies from 1996 to 2011. Recommendations were formulated based on that evidence and on the expert opinion of Cancer Care Ontario’s Head and Neck Cancer disease site group. The systematic review and practice guideline were externally reviewed by practitioners in Ontario, Canada.

Results

The available evidence was of a level insufficient to demonstrate a clear difference between treatment options when considering the likelihood of local control or overall survival. Although the evidence was mainly retrospective, there was a suggestion that, compared with surgery, radiotherapy might be associated with less measureable perturbation of voice without a significant difference in patient perception. The likelihood of laryngeal preservation may be higher when surgery can be offered as initial treatment.

Conclusions

For patients with early (T1) glottic cancer, the evidence is insufficient to demonstrate a difference between endolaryngeal surgery (with or without laser) and external-beam radiation therapy. The choice between treatment modalities has been based on patient and clinician preferences and general medical condition.     

A phase II evaluation of a 3-hour infusion of paclitaxel, cisplatin, and 5-fluorouracil in patients with advanced or recurrent squamous cell carcinoma of the head and neck: Southwest Oncology Group study 0007

BACKGROUND: Previous data from an institutional pilot study in patients with advanced or recurrent squamous cell carcinoma of the head and neck (SCCHN) who received treated a combined chemotherapy regimen of paclitaxel, cisplatin, and 5-fluorouracil indicated an overall response rate of 60% and a median survival of 6 months. To validate these results and to determine the feasibility of this combination, a Phase II study was conducted by the Southwest Oncology Group (SWOG S0007). METHODS: Patients with advanced or recurrent SCCHN were eligible if they had received 1 previous regimen of induction/adjuvant chemotherapy or no prior systemic therapy. Patients received treatment with paclitaxel (135 mg/m(2) on Day 1), followed by cisplatin (75 mg/m(2) on Day 1), and 5-fluorouracil (1000 mg/m(2)per day as a 96-hour continuous infusion on Days 1-4) every 21 days. RESULTS: Seventy-six patients received a combined total of 286 cycles of chemotherapy. Sixty-nine patients were evaluable for response. There were 5 complete responses (7%) and 23 partial responses (33%) partial responses, for an overall response rate of 41%. The median progression-free survival was 4 months, and the median overall survival was 10 months. Six treatment-related deaths were documented, including deaths in 2 patients who had a Zubrod PS of 2. Grade 3 or 4 neutropenia (according to National Cancer Institute Common Toxicity Criteria [version 2.0]) was observed in 47% of patients. Other Grade 3 or 4 adverse events included mucositis (34% of patients), nausea (20% of patients), anemia (9% of patients), and neuropathy (8% of patients). CONCLUSIONS: The combination of paclitaxel, cisplatin, and 5-fluorouracil had efficacy similar to that of standard treatment regimens in patients with advanced or recurrent SCCHN but with increased toxicity.     

Poly (ADP-ribose) polymerase 3 (PARP3), a potential repressor of telomerase activity

Background

Considering previous result in Non-Small Cell Lung Cancer (NSCLC), we investigated in human cancer cells the role of PARP3 in the regulation of telomerase activity.

Methods

We selected A549 (lung adenocarcinoma cell line) and Saos-2 (osteosarcoma cell line), with high and low telomerase activity levels, respectively. The first one was transfected using a plasmid construction containing a PARP3 sequence, whereas the Saos-2 cells were submitted to shRNA transfection to get PARP3 depletion. PARP3 expression on both cell systems was evaluated by real-time quantitative PCR and PARP3 protein levels, by Western-blot. Telomerase activity was determined by TRAP assay.

Results

In A549 cells, after PARP3 transient transfection, data obtained indicated that twenty-four hours after transfection, up to 100-fold increased gene expression levels were found in the transfected cells with pcDNA/GW-53/PARP3 in comparison to transfected cells with the empty vector. Moreover, 48 hours post-transfection, telomerase activity decreased around 33%, and around 27%, 96 hours post-transfection. Telomerase activity average ratio was 0.67 ± 0.05, and 0.73 ± 0.06, respectively, with significant differences. In Saos-2 cells, after shRNA-mediated PARP3 silencing, a 2.3-fold increase in telomerase activity was detected in relation to the control.

Conclusion

Our data indicated that, at least in some cancer cells, repression of PARP3 could be responsible for an increased telomerase activity, this fact contributing to telomere maintenance and, therefore, avoiding genome instability.     

Breast and cervical cancer screening behaviours among colorectal cancer survivors in Nova Scotia

Purpose

We analyzed patterns and factors associated with receipt of breast and cervical cancer screening in a cohort of colorectal cancer survivors.

Methods

Individuals diagnosed with colorectal cancer in Nova Scotia between January 2001 and December 2005 were eligible for inclusion. Receipt of breast and cervical cancer screening was determined using administrative data. General-population age restrictions were used in the analysis (breast: 40–69 years; cervical: 21–75 years). Kaplan–Meier and Cox proportional hazards models were used to assess time to first screen.

Results

Of 318 and 443 colorectal cancer survivors eligible for the breast and cervical cancer screening analysis respectively, 30.1% [95% confidence interval (ci): 21.2% to 39.0%] never received screening mammography, and 47.9% (95% ci: 37.8% to 58.0%) never received cervical cancer screening during the study period. Receipt of screening before the colorectal cancer diagnosis was strongly associated with receipt of screening after diagnosis (hazard ratio for breast cancer screening: 4.71; 95% ci: 3.42 to 6.51; hazard ratio for cervical cancer screening: 6.83; 95% ci: 4.58 to 10.16).

Conclusions

Many colorectal cancer survivors within general-population screening age recommendations did not receive breast and cervical cancer screening. Future research should focus on survivors who meet age recommendations for population-based cancer screening.     

Evaluation of an alpha agonist alone and in combination with a nonsteroidal antiinflammatory agent in the treatment of experimental rhinovirus colds.

The pathogenesis of symptoms of the common cold and their optimal treatment are incompletely understood. To evaluate the role of an oral alpha agonist alone and in combination with a nonsteroidal anti-inflammatory drug in the treatment of experimental rhinovirus colds, 58 subjects were randomized to receive pseudoephedrine 60 mg alone, pseudoephedrine 60 mg plus ibuprofen 200 mg, or placebo, four times daily for 4 1/2 days beginning 30 hours after intranasal rhinovirus inoculation under double-blind conditions. The frequencies of infection, colds occurrence, and viral shedding did not differ significantly between the groups. Total symptom scores were reduced by 59% by pseudoephedrine plus ibuprofen (p less than 0.05) and 48% by pseudoephedrine alone compared with placebo. Nasal symptom scores tended to be lower in recipients of pseudoephedrine plus ibuprofen compared with pseudoephedrine alone (p = 0.09), but other parameters showed no significant treatment differences between the groups. Rhinorrhea, as determined by nasal secretion weights, was significantly reduced in both treatment groups compared to placebo. Nasal patency measurements tended to show the greatest improvement in recipients of pseudoephedrine plus ibuprofen. Therapy was clinically well tolerated. The results suggest that an oral alpha agonist is effective in modifying certain manifestations of experimental rhinovirus infection and that the addition of a nonsteroidal anti-inflammatory drug may provide additional benefit in nasal symptoms and patency. Studies involving large numbers of patients with natural colds are needed to determine the clinical significance of these findings.     

Breast cancer oral anti-cancer medication adherence: a systematic review of psychosocial motivators and barriers

Purpose

In the past decade, there has been an increase in the development and use of oral anti-cancer medications (OAMs), especially for breast cancer–the most prevalent cancer in women. However, adherence rates for OAMs are often suboptimal, leading to lower survival rate, increased risk of recurrence, and higher healthcare costs. Our goal was to identify potentially modifiable psychosocial facilitators and barriers that may be targeted to increase OAM adherence for breast cancer patients.

Methods

We systematically searched PubMed for studies published in the U.S. by June 15, 2016 that addressed the following: (1) OAMs for breast cancer; (2) medication adherence; and (3) at least one psychosocial aspect of adherence.

Results

Of the 1752 papers screened, 21 articles were included and analyzed. The most commonly reported motivators for adherence are patient-provider relationships (n = 11 studied, 82% reported significant association) and positive views and beliefs of medication (n = 9 studied, 89% reported significant association). We also identified consistent evidence of the impact of depression and emotions, perception of illness, concern of side effects, self-efficacy in medication management and decision making, knowledge of medication, and social support on OAM adherence.

Conclusions

Compared to traditional demographic, system, and clinical-related factors that have been well documented in the literature but are not easily changed, these cognitive, psychological, and interpersonal factors are more amendable via intervention and therefore could generate greater benefit in improving patient compliance and health outcomes. As OAMs shift treatment administration responsibility onto patients, continuous provider communication and education on illness and regimen are the keys to supporting patients’ medication behavior.

     

Young women's perspectives on cervical cancer prevention in Appalachian Kentucky

Human papillomavirus (HPV) vaccination coupled with routine Papanicolaou (Pap) tests can prevent pervasive HPV infections causing cervical cancer. However, both HPV vaccination rates and Pap testing rates in Appalachian Kentucky are lower among all age groups than the rest of the United States. We recruited 19 young women residing in Appalachian Kentucky from university-based and rural clinical settings for group and individual interviews. After considering an integrated behavioral framework, we illustrate these women's perspectives by detailing five themes, including (a) experiential beliefs pose barriers to performing behaviors, (b) three vaccine doses complicate vaccination intention, (c) women have misunderstandings about HPV and the HPV vaccination function, (d) normative influences cue action (and inaction), and (e) specific environmental and contextual barriers exist to performing cervical cancer prevention behaviors in Appalachian Kentucky. These findings related to cervical cancer prevention in Appalachian Kentucky have implications for health-message design and clinical practice.     

A critical assessment of docking programs and scoring functions

Docking is a computational technique that samples conformations of small molecules in protein binding sites; scoring functions are used to assess which of these conformations best complements the protein binding site. An evaluation of 10 docking programs and 37 scoring functions was conducted against eight proteins of seven protein types for three tasks: binding mode prediction, virtual screening for lead identification, and rank-ordering by affinity for lead optimization. All of the docking programs were able to generate ligand conformations similar to crystallographically determined protein/ligand complex structures for at least one of the targets. However, scoring functions were less successful at distinguishing the crystallographic conformation from the set of docked poses. Docking programs identified active compounds from a pharmaceutically relevant pool of decoy compounds; however, no single program performed well for all of the targets. For prediction of compound affinity, none of the docking programs or scoring functions made a useful prediction of ligand binding affinity.