Reporting of tobacco use and impact on outcomes in cancer cooperative group clinical trials: A systematic scoping review.

40 Background: Continued smoking after a diagnosis of cancer negatively impacts cancer outcomes but the impact of tobacco on many innovative treatments has not yet been well established. Collecting and evaluating tobacco use in cancer clinical trials may advance understanding of the consequences of tobacco use on specific treatment modalities. We performed a systematic scoping review of the frequency of reporting and analysis of tobacco use in clinical trials run by cancer cooperative clinical trial groups. Methods: A comprehensive literature search was conducted to identify cancer cooperative group clinical trials published from January 2017 to October 2019 using Medline, Epub Ahead of Print and In-Process & Other Non-Indexed Citations, Embase, Cochrane Central Register of Controlled Trials using OvidSP. Eligible studies evaluated either systemic and/or radiation therapies, involved at least one cancer cooperative group, included > 100 adult patients and reported on at least one primary or secondary endpoint, which included overall survival (OS), disease/progression-free survival (DFS/PFS), response rates, toxicities/adverse events, or quality of life (QoL). Secondary analyses of previously published trials were excluded. Results: Among 14843 identified studies, 91 studies representing 90 trials met inclusion criteria. 24% were phase II trials, 2% phase II/III and 74% phase III. Trial start dates ranged from 1995-2015 with most (29%) between 2007-2008; median trial sample size was 406 (range: 100-4994); 86% involved systematic therapy, 35% involved radiation; 14% were lung and 5% were head and neck trials. 51% of trials had a curative intent, 33% were palliative and 16% involved hematologic cancers. 74 studies reported on OS, 73 DFS/PFS, and 88 toxicity/QoL. 19 studies reported baseline tobacco use information, while two reported collecting follow-up tobacco use. Of those collecting baseline tobacco use, only 7 reported any analysis of the impact of tobacco on clinical outcomes. There was significant heterogeneity in the reporting of baseline tobacco use: 5 reported never/ever status, 10 reported never/ex-smoker/current smoker status; 4 reported some measure of smoking intensity; none reported on verifying smoking status or second hand smoke exposure. Trials of tobacco related (lung and head and neck) cancers were more likely to report baseline tobacco use compared to non-tobacco related cancers (83% vs 6% p < 0.001). Conclusions: Few cancer cooperative group clinical trials report and analyze trial participants’ baseline tobacco use, and even fewer collect follow up information. Significant heterogeneity exists in reporting tobacco use. Routine standardized collection and reporting of tobacco use, both at baseline and follow up in clinical trials, should be implemented to enable investigators to evaluate the clinical impact of tobacco use on new cancer therapies.

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Tobacco Assessment in Actively Accruing National Cancer Institute Cooperative Group Program Clinical Trials

Journal of Clinical Oncology ◽

10.1200/jco.2011.40.8815 ◽

2012 ◽

Vol 30 (23) ◽

pp. 2869-2875 ◽

Cited By ~ 31

Author(s):

Erica N. Peters ◽

Essie Torres ◽

Benjamin A. Toll ◽

K. Michael Cummings ◽

Ellen R. Gritz ◽

...

Keyword(s):

Clinical Trials ◽

Cancer Treatment ◽

Treatment Outcomes ◽

Tobacco Use ◽

Phase Iii ◽

Cooperative Group ◽

Group Program ◽

Status Assessment ◽

Oncology Practice

Purpose Substantial evidence suggests that tobacco use has adverse effects on cancer treatment outcomes; however, routine assessment of tobacco use has not been fully incorporated into standard clinical oncology practice. The purpose of this study was to evaluate tobacco use assessment in patients enrolled onto actively accruing cancer clinical trials. Methods Protocols and forms for 155 actively accruing trials in the National Cancer Institute's (NCI's) Clinical Trials Cooperative Group Program were evaluated for tobacco use assessment at enrollment and follow-up by using a structured coding instrument. Results Of the 155 clinical trials reviewed, 45 (29%) assessed any form of tobacco use at enrollment, but only 34 (21.9%) assessed current cigarette use. Only seven trials (4.5%) assessed any form of tobacco use during follow-up. Secondhand smoke exposure was captured in 2.6% of trials at enrollment and 0.6% during follow-up. None of the trials assessed nicotine dependence or interest in quitting at any point during enrollment or treatment. Tobacco status assessment was higher in lung/head and neck trials as well as phase III trials, but there was no difference according to year of starting accrual or cooperative group. Conclusion Most actively accruing cooperative group clinical trials do not assess tobacco use, and there is no observable trend in improvement over the past 8 years. Failure to incorporate standardized tobacco assessments into NCI-funded Cooperative Group Clinical Trials will limit the ability to provide evidence-based cessation support and will limit the ability to accurately understand the precise effect of tobacco use on cancer treatment outcomes.

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BiovaxID™ Vaccine Therapy of Follicular Lymphoma in First Remission: Long-Term Follow-Up of a Phase II Trial and Status of a Controlled, Randomized Phase III Trial.

Blood ◽

10.1182/blood.v106.11.2441.2441 ◽

2005 ◽

Vol 106 (11) ◽

pp. 2441-2441 ◽

Cited By ~ 8

Author(s):

Carlos Santos ◽

Lee Stern ◽

Laura Katz ◽

Thelma Watson ◽

Gause Barry

Keyword(s):

Clinical Trial ◽

Phase Ii ◽

Disease Free Survival ◽

T Cell Response ◽

Phase Iii ◽

Patient Specific ◽

Free Survival ◽

The Impact ◽

Disease Free

Abstract Malignant B-cells in Follicular Non-Hodgkin’s Lymphoma expresses a clonal idiotype immunoglobulin which can serve as the basis for a patient-specific anti-idiotype vaccine. In a previous single-arm Phase II study by Bendandi, et al (Nature Med5:1171–1177, 1999), we evaluated the ability of tumor-specific idiotype (Id) conjugated to keyhole limpet hemocyanin (KLH) administered concurrently with granulocyte-monocyte colony-stimulating factor (GM-CSF) adjuvant to induce complete remissions and molecular remissions in treated patients. The vaccine formulation induced a tumor-specific cytotoxic CD8+ and CD4+ T-cell response in patients in first complete remission after standard chemotherapy, as well as achieved molecular remissions in 8 of 11 of these patients. Data available at the time of this abstract for the 20-patient cohort, indicates a median follow-up of 9.167 years. 9 patients (45 %) remain in continuous first CR at their most recent follow-up (either in 2004 or 2005), and overall survival is 95%. The data further indicates the median disease free survival for the cohort is 96.5 months (8.04 years). To date there have been no additional reported mortalities in this cohort. As of August 2005, we report the progress of the Phase III clinical trial for this vaccine, opened in January 2000 by the NCI to evaluate the impact of this hybridoma-based Id vaccine on disease-free survival in a group of up to 375 previously untreated patients who have attained a CR or CRu from PACE [Prednisone, Doxorubicin, Cyclophosphamide, and Etoposide (ProMACE without methotrexate)] chemotherapy, and who are randomized to receive either vaccine or control. To date, 187 patients have been accrued onto the study. Of those patients, 145 (77.5%) achieved a CR or Cru and are being followed in this ongoing clinical trial.

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Cetuximab in the Treatment of Locally Advanced Head and Neck Cancer

European Oncology & Haematology ◽

10.17925/eoh.2011.07.01.16 ◽

2011 ◽

Vol 07 (01) ◽

pp. 16

Author(s):

Rainald Knecht ◽

Keyword(s):

Quality Of Life ◽

Clinical Trials ◽

Head And Neck ◽

Phase Ii ◽

Locally Advanced ◽

Phase Iii ◽

Significant Advance ◽

Life Questionnaire ◽

Large Phase

Locally advanced squamous cell cancer of the head and neck (LA SCCHN) includes various cancers of the oral cavity, pharynx and larynx that have spread from the primary site but have not metastasised. Due to poor public awareness of SCCHN and its symptoms, about 5070% of cases are diagnosed only when the disease has become locally advanced; prognosis by this time is poorer than during earlier stages. Combinations of chemotherapy with radiotherapy have produced greater efficacy in treating LA SCCHN over radiotherapy alone in various clinical trials, but this approach increases the incidence of toxicities. An alternative therapeutic approach is to use the monoclonal antibody cetuximab (Erbitux®). Cetuximab targets epidermal growth factor receptor (EGFR), which is overexpressed in LA SCCHN, and this overexpression of EGFR is associated with poor prognosis. A number of recent phase II and III clinical trials have demonstrated that cetuximab is an effective and safe treatment for LA SCCHN. One large phase III clinical trial demonstrated that the addition of cetuximab to radiotherapy in patients with LA SCCHN provides substantial efficacy and quality of life benefits, including improvements in overall survival, disease-free survival, response rate and European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 parameters, without markedly affecting safety and tolerability. Other, smaller phase II studies in patient populations having either resectable or non-resectable tumours have demonstrated the benefits of adding cetuximab to other chemotherapy/radiotherapy regimens for LA SCCHN. Cetuximab is currently the only targeted biological therapy approved for use in combination with radiation therapy for LA SCCHN. In conclusion, cetuximab represents a significant advance in the treatment of LA SCCHN. Furthermore, based on the data from the large phase III trial, the most recent European Society for Medical Oncology (ESMO) guidelines recommend the use of cetuximab in combination with radiotherapy in LA SCCHN.

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Patient-Reported Outcomes in Phase II Cancer Clinical Trials: Lessons Learned and Future Directions

Journal of Clinical Oncology ◽

10.1200/jco.2007.11.7275 ◽

2007 ◽

Vol 25 (32) ◽

pp. 5058-5062 ◽

Cited By ~ 27

Author(s):

Lynne I. Wagner ◽

Lari Wenzel ◽

Edward Shaw ◽

David Cella

Keyword(s):

Clinical Trials ◽

Phase Ii ◽

Symptom Management ◽

Patient Reported Outcomes ◽

Phase Iii ◽

Cancer Clinical Trials ◽

Phase Ii Trials ◽

Patient Reported ◽

Phase Iii Trials ◽

The Impact

With increasing limits on the resources available to conduct cancer clinical trials, the inclusion of patient-reported outcomes (PROs) in treatment and symptom management trials must be prioritized. Although it has been suggested on occasion that phase III trials should take precedence over phase II trials, we argue that there is a clear and important role for PRO assessment in phase II trials going forward. To illustrate the value realized from including PROs in phase II trials, we provide case examples from cancer treatment and supportive care. The benefits of including PROs in symptom management intervention research are exemplified using phase II trials targeting cognitive impairment. The inclusion of PROs in phase II cancer clinical trials adds important information about the impact of treatment in health-related quality of life, and advances the science of PRO measurement. These contributions significantly enhance the design of phase III trials, ultimately leading to the efficient utilization of clinical trial resources.

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A phase II trial design with direct assignment option for initial marker validation.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.30_suppl.34 ◽

2012 ◽

Vol 30 (30_suppl) ◽

pp. 34-34 ◽

Cited By ~ 1

Author(s):

Sumithra J. Mandrekar ◽

Ming-Wen An ◽

Daniel J. Sargent

Keyword(s):

Clinical Trials ◽

Phase Ii ◽

Type I Error ◽

Predictive Biomarkers ◽

Stage Ii ◽

Phase Iii ◽

Type I ◽

Design Strategies ◽

Number Of Patients ◽

The Impact

34 Background: Phase II clinical trials aim to identify promising experimental regimens for further testing in phase III trials. Testing targeted therapies with predictive biomarkers mandates efficient trial designs. Current biomarker-based trial designs, including the enrichment, all-comers, and adaptive designs, randomize patients to receive treatment or not throughout the entire duration of the trial. Recognizing the need for randomization yet acknowledging the possibility of promising but nonconclusive results after a preplanned interim analysis (IA), we propose a two-stage phase II design that allows for the possibility of direct assignment (i.e., stop randomization and assign all patients to the experimental arm in stage II) based on IA results. Methods: Using simulations, we compared properties of the direct assignment option design to a 1:1 randomized phase II design and assessed the impact of the timing of IA (after 33%, 50%, or 67% of accrual) and number of IA (one versus two with option for direct assignment at the first and second) over a range of response rate ratios (between 1.0 and 3.0). Results: Between 12% and 30% of the trials (out of 6,000 simulated trials) adopt direct assignment in stage II, with direct adoption depending on the treatment effect size and specified type I error rate (TIER). The direct assignment option design has minimal loss in power (<1.8%) and minimal increase in T1ER (<2.1%) compared to a 1:1 randomized design. The maximum loss in power across possible timings of IA was <1.2%. For the direct assignment option design, there was a 20%-50% increase in the number of patients treated on the experimental (vs. control) arm for the 1 IA case, and 40%-100% increase for the 2 IA case. Conclusions: Testing predictive biomarkers in clinical trials requires new design strategies. In the spectrum of phase II designs from adaptive to balanced randomized all-comers or enrichment designs, the direct assignment design provides a middle ground with desirable statistical properties that may appeal to both clinicians and patients.

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OA10.03 Reporting of Tobacco Use and Impact on Outcomes in Cancer Cooperative Group Clinical Trials: A Systematic Scoping Review

Journal of Thoracic Oncology ◽

10.1016/j.jtho.2021.01.309 ◽

2021 ◽

Vol 16 (3) ◽

pp. S123-S124

Author(s):

L. Eng ◽

J. Brual ◽

A. Nagee ◽

S. Mok ◽

R. Fazelzad ◽

...

Keyword(s):

Clinical Trials ◽

Tobacco Use ◽

Scoping Review ◽

Cooperative Group

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Empiric proton pump inhibitor therapy after esophageal food impaction may mask eosinophilic esophagitis diagnosis at follow-up

Diseases of the Esophagus ◽

10.1093/dote/doab030 ◽

2021 ◽

Author(s):

Luke Hillman ◽

Sarah Donohue ◽

Aimee Teo Broman ◽

Patrick Hoversten ◽

Eric Gaumnitz ◽

...

Keyword(s):

Proton Pump Inhibitor ◽

Proton Pump ◽

Eosinophilic Esophagitis ◽

Empiric Therapy ◽

Proton Pump Inhibitor Therapy ◽

Significant Heterogeneity ◽

Food Impaction ◽

Esophageal Food Impaction ◽

The Impact

Summary Esophageal food impaction (EFI) is often the first presentation for patients with eosinophilic esophagitis (EoE); however, there is significant heterogeneity in the management of EFI. We aimed to study the impact of EFI management, particularly post-EFI medication prescriptions on EoE diagnosis, follow-up, and recurrence in patients with endoscopic features of EoE. In our retrospective study, adults presenting between 2007 and 2017 with EFI requiring endoscopic dis-impaction with endoscopic features of EoE (furrows, rings, and/or exudates) were included. We examined the impact of demographics and EFI management on EoE diagnosis, follow-up (esophagogastroduodenoscopy [EGD] or clinic visit within 6 months), and recurrence. We identified 164 cases of EFI due to suspected EoE. Biopsy was performed in 68 patients (41.5%), and 144 patients (87.8%) were placed on proton pump inhibitor (PPI) and/or swallow corticosteroids after EFI, including 88.5% of those not biopsied. PPI use at time of biopsy was negatively associated with EoE diagnosis (odds ratio: 0.39, confidence interval: 0.17–0.85). Sixty-one (37.4%) patients were lost to follow-up at 6 months. Recurrent EFI at 1 year occurred in 3.7% of patients. Medications, most commonly PPI, are frequently prescribed after EFI when the endoscopic features of EoE are present, which may mask the diagnosis of EoE on follow-up EGD. We estimated that for every five patients biopsied on PPI, one case of EoE is masked. As recurrent EFI within 1 year is uncommon, empiric therapy should be avoided until diagnostic biopsies are obtained. Further efforts to reduce loss to follow-up after EFI are also needed.

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Unconventional Anticancer Agents: A Systematic Review of Clinical Trials

Journal of Clinical Oncology ◽

10.1200/jco.2005.03.8406 ◽

2006 ◽

Vol 24 (1) ◽

pp. 136-140 ◽

Cited By ~ 20

Author(s):

Andrew J. Vickers ◽

Joyce Kuo ◽

Barrie R. Cassileth

Keyword(s):

Clinical Trials ◽

Phase I ◽

Cancer Patients ◽

Phase Ii ◽

Dose Finding ◽

Phase Iii ◽

High Dose ◽

Free Text ◽

Phase Ii Trials ◽

Off Label

Purpose A substantial number of cancer patients turn to treatments other than those recommended by mainstream oncologists in an effort to sustain tumor remission or halt the spread of cancer. These unconventional approaches include botanicals, high-dose nutritional supplementation, off-label pharmaceuticals, and animal products. The objective of this study was to review systematically the methodologies applied in clinical trials of unconventional treatments specifically for cancer. Methods MEDLINE 1966 to 2005 was searched using approximately 200 different medical subject heading terms (eg, alternative medicine) and free text words (eg, laetrile). We sought prospective clinical trials of unconventional treatments in cancer patients, excluding studies with only symptom control or nonclinical (eg, immune) end points. Trial data were extracted by two reviewers using a standardized protocol. Results We identified 14,735 articles, of which 214, describing 198 different clinical trials, were included. Twenty trials were phase I, three were phase I and II, 70 were phase II, and 105 were phase III. Approximately half of the trials investigated fungal products, 20% investigated other botanicals, 10% investigated vitamins and supplements, and 10% investigated off-label pharmaceuticals. Only eight of the phase I trials were dose-finding trials, and a mere 20% of phase II trials reported a statistical design. Of the 27 different agents tested in phase III, only one agent had a prior dose-finding trial, and only for three agents was the definitive study initiated after the publication of phase II data. Conclusion Unconventional cancer treatments have not been subject to appropriate early-phase trial development. Future research on unconventional therapies should involve dose-finding and phase II studies to determine the suitability of definitive trials.

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A Review of Marital Intimacy-Enhancing Interventions among Married Individuals

Global Journal of Health Science ◽

10.5539/gjhs.v8n8p74 ◽

2015 ◽

Vol 8 (8) ◽

pp. 74 ◽

Cited By ~ 4

Author(s):

Maryam Kardan-Souraki ◽

Zeinab Hamzehgardeshi ◽

Ismail Asadpour ◽

Reza Ali Mohammadpour ◽

Soghra Khani

Keyword(s):

Clinical Trials ◽

Randomized Controlled Trials ◽

Cochrane Library ◽

Controlled Trials ◽

Main Concern ◽

Care Providers ◽

Marital Intimacy ◽

Randomized Controlled ◽

The Impact

BACKGROUND: Lack of intimacy is currently the main concern rather than main concern of the experts in psychology and counseling. It is considered as one of the most important causes for divorce and as such to improve marital intimacy a great number of interventions have been proposed in the literature. Intimacy training and counseling make the couples take effective and successful steps to increase marital intimacy. No study has reviewed the interventions promoting marital intimacy after marriage. Thus, this review study aimed to classify the articles investigating the impact of interventional programs on marital intimacy after marriage.SEARCH METHODS: In April 2015, we performed a general search in Google Scholar search engines, and then we did an advanced search the databases of Science Direct, ProQuest, SID, Magiran, Irandoc, Pubmed, Scopus, <a href="http://www.cochranelibrary.com/">Cochrane Library</a>, and Psych info; Cumulative Index to Nursing and Allied Health Literature (CINAHL). Also, lists of the references of the relevant articles were reviewed for additional citations. Using Medical Subject Headings (MESH) keywords: Intervention (Clinical Trials, Non-Randomized Controlled Trials, Randomized Controlled Trials, Education), intimacy, marital (Marriage) and selected related articles to the study objective were from 1995 to April 2015. Clinical trials that evaluated one or more behavioral interventions to improve marital intimacy were reviewed in the study.MAIN RESULTS: 39 trials met the inclusion criteria. Eleven interventions had follow-up, and 28 interventions lacked follow-up. The quality evidence for 22 interventions was low, for 15 interventions moderate, and for one intervention was considered high. Findings from studies were categorized in 11 categories as the intimacy promoting interventions in dimensions of emotional, psychological, physical, sexual, temporal, communicational, social and recreational, aesthetic, spiritual, intellectual intimacy, and total intimacy.AUTHORS’ CONCLUSIONS: Improving and promoting communication, problem solving, self-disclosure and empathic response skills and sexual education and counseling in the form of cognitive-behavioral techniques and based on religious and cultural context of each society, an effective step can be taken to enhance marital intimacy and strengthen family bonds and stability. Health care providers should consider which interventions are appropriate to the couple characteristics and their relationships.

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