Treatment of cancer with radiation and drugs.

1996 ◽  
Vol 14 (12) ◽  
pp. 3156-3174 ◽  
Author(s):  
I F Tannock
Keyword(s):  
Randomized Trials ◽  
Combined Treatment ◽  
Therapeutic Index ◽  
Clinical Results ◽  
Therapeutic Benefit ◽  
Current Status ◽  
Combined Modality Treatment ◽  
Normal Tissues ◽  
Tissue Microenvironment ◽  
Meta Analyses

PURPOSE To review the current status and future prospects of combined treatment of cancer with radiation and drugs. DESIGN A review of (1) mechanisms whereby combined use of radiation and drugs might lead to improved therapeutic benefit for the treatment of cancer; (2) problems related to the design and analysis of clinical trials that evaluate combined modality treatment; and (3) clinical results of larger randomized trials that have compared combined versus single modality treatment for various types of cancer. RESULTS Improvement in the therapeutic index depends on exploitation of the biologic properties that differ between tumors and normal tissues; such properties may include mechanisms of resistance to radiation and drugs, tissue microenvironment, and cell proliferation or repopulation during radiotherapy. To detect or rule out the small but clinically important differences in outcome that might occur will require the performance of large, randomized, controlled trials or patient-based meta-analyses; single-arm studies, small randomized trials, and subgroup analyses of larger trials can generate hypotheses. Clinical gains from combined treatment have been demonstrated in a few sites, with disappointing results in others. In general, more promising results have accrued from concurrent treatment, despite greater toxicity, than from sequential use of drugs and radiation. CONCLUSION Clinical gains from combined treatment with radiation and drugs have been small. New, mechanistically based approaches to combined treatment are required.

Altered Fractionation in Radiotherapy

1998 ◽  
Vol 84 (2) ◽  
pp. 155-159 ◽  
Author(s):  
Riccardo Valdagni
Keyword(s):  
Treatment Time ◽  
Clinical Results ◽  
Therapeutic Benefit ◽  
Phase Iii ◽  
Overall Treatment Time ◽  
Conventional Fractionation ◽  
Normal Tissues ◽  
Normal Tissue Damage ◽  
Altered Fractionation ◽  
Cell Repopulation

Differences between late-responding (slowly proliferating) normal tissues and early-responding (rapidly proliferating) normal tissues and tumor cells and the event of tumor cell repopulation occurring during treatment have essentially led to the development of altered fractionation schemes. Altered fractionation regimens mainly refer to schedules utilising two or more (small dose) fractions per day for part of or for the entire treatment course. It must be underlined that a true standard or conventional fractionation regimen does not exist: no schedule is universally recognised as the standard of reference to be compared with. However, continental European and U.S. conventional regimens are the considered control arm with which the new experimental regimens have to be compared. For this reason they are generally recognised as the standards. The basic rationale for hyperfractionated or accelerated regimens respectively lies in the possibility (a) to deliver higher total doses reducing late-responding normal tissue damage, (b) to deliver total doses in a reduced overall treatment time to defeat tumor clonogen repopulation. Multiple fractions per day should not be delivered with interfraction intervals smaller than 6 hours. Clinical results of phase I-II and limited but convincing phase III randomised trials suggest that a therapeutic benefit can be achieved with new altered regimens.

Thymidylate synthase inhibitors in cancer therapy: direct and indirect inhibitors.

1997 ◽  
Vol 15 (1) ◽  
pp. 389-400 ◽  
Author(s):  
Y M Rustum ◽  
A Harstrick ◽  
S Cao ◽  
U Vanhoefer ◽  
M B Yin ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Clinical Evaluation ◽  
Thymidylate Synthase ◽  
Dihydropyrimidine Dehydrogenase ◽  
Therapeutic Index ◽  
Clinical Results ◽  
New Drugs ◽  
Phase Iii ◽  
Normal Tissues ◽  
High Level

PURPOSE AND METHODS Although fluoropyrimidines, in particular, fluorouracil (5-FU) and fluorodeoxyuridine (FdUrd), are active alone and in combination with other agents in a variety of human malignancies, therapeutic selectivity, resistance, and efficacy have been a major limitation in cancer therapy. Preclinical and clinical results in advanced and adjuvant colorectal cancers confirmed that the therapeutic efficacy of fluoropyrimidines, with thymidylate synthase (TS) as a primary target, can be improved significantly with leucovorin (LV) modulation. With the recognition that TS is an important therapeutic target, direct and specific inhibitors have been developed and are under intensive preclinical and clinical evaluation, primarily in patients with colorectal cancer, with demonstrable activity. The direct TS inhibitors have been shown to be potent, with a high level of specificity under therapeutic conditions for TS. This includes ZD1694, AG337, and LY231514. To date, although the therapeutic activity of both direct and indirect inhibitors of TS is similar, differences in the magnitude and profile of toxicity have been observed. A phase III comparative evaluation of a direct inhibitor of TS (ZD1694) with an indirect inhibitor (5-FU/LV) has been completed and showed similar activity but reduced toxicity in favor of ZD1694. RESULTS Recognition that greater than 95% of the injected dose of 5-FU is rapidly inactivated by dihydropyrimidine dehydrogenase (DPD) to therapeutically inactive products, but with toxicity to normal tissues, led to the development of inhibitors of this enzyme with the aim to modify the therapeutic index of 5-FU. Several inhibitors in combination with 5-FU are under preclinical and clinical evaluation, including uracil and 5-chloro-2,4-dihydroxy pyridine, as modulators of 5-FU derived from its prodrug tegafur and 5-ethynyluracil as a modulator of 5-FU. CONCLUSION In this review, an update of the present status of direct and indirect inhibitors of TS is discussed, as well as the future prospect for new drugs alone and in combination.

Cytoprotective Agents to Avoid Chemotherapy Induced Sideeffects on Normal Cells: A Review

2019 ◽  
Vol 19 (10) ◽  
pp. 765-781
Author(s):  
Seema Rohilla ◽  
Harish Dureja ◽  
Vinay Chawla
Keyword(s):  
Adverse Effects ◽  
Anticancer Agents ◽  
Therapeutic Index ◽  
Chemotherapeutic Agents ◽  
Vital Role ◽  
Normal Cells ◽  
Normal Tissues ◽  
Organ Specific ◽  
Delay In Treatment

Anticancer agents play a vital role in the cure of patients suffering from malignancy. Though, the chemotherapeutic agents are associated with various adverse effects which produce significant toxic symptoms in the patients. But this therapy affects both the malignant and normal cells and leads to constricted therapeutic index of antimalignant drugs which adversely impacts the quality of patients’ life. Due to these adversities, sufficient dose of drug is not delivered to patients leading to delay in treatment or improper treatment. Chemoprotective agents have been developed either to minimize or to mitigate the toxicity allied with chemotherapeutic agents. Without any concession in the therapeutic efficacy of anticancer drugs, they provide organ specific guard to normal tissues.

Is Atherothromboaspiration a Possible Solution for the Prevention of No-Reflow Phenomenon in Acute Coronary Syndromes? Single Centre Experience and Review of the Literature

2019 ◽  
Vol 17 (2) ◽  
pp. 164-179
Author(s):  
Antonis S. Manolis
Keyword(s):  
Coronary Intervention ◽  
Covered Stent ◽  
Current Status ◽  
Extensive Literature ◽  
Review Of The Literature ◽  
Single Centre ◽  
Total N ◽  
No Reflow ◽  
Clinical Benefits ◽  
Meta Analyses

Background: Intracoronary thrombus in acute Myocardial Infarction (MI) confers higher rates of no-reflow with attendant adverse consequences. Earlier Randomized-Controlled-Trials (RCTs) of routine thromboaspiration during Percutaneous Coronary Intervention (PCI) indicated a clinical benefit, but more recent RCTs were negative. However, data of selective use of this adjunctive approach remain scarce. </P><P> Objective: The aim of this single-centre prospective study was to report the results of selective thromboaspiration during PCI in patients with intracoronary thrombi, and also to provide an extensive literature review on current status of thromboaspiration. </P><P> Methods: The study included 90 patients (77 men; aged 59.3±12.7 years) presenting with acute MI (STElevation MI (STEMI) in 74, non-STEMI in 16) who had intracoronary thrombi and were submitted to thromboaspiration. </P><P> Results: Total (n=67) or subtotal (n=18) vessel occlusions were present in 85 (94%) patients. Thromboaspiration and subsequent PCI were successful in 89/90 (98.9%) patients, with coronary stenting in 86 (96.6%). In 4 patients with residual thrombus, a mesh-covered stent was implanted. IIb/IIIa-inhibitors were administered in 57 (63.3%) patients. No-reflow occurred in only 1 (1.1%) patient. The postprocedural course was uneventful. Review of the literature revealed several early observational and RCTs and meta-analyses favouring manual, not mechanical, thrombectomy. However, newer RCTs and meta-analyses significantly curtailed the initial enthusiasm for the clinical benefits of routine use of thromboaspiration. </P><P> Conclusion: Selective thromboaspiration for angiographically visible thrombi in MI patients undergoing PCI, as an adjunct to mechanical reperfusion and to IIb/IIIa-inhibitors, may be an option since this manoeuvre may improve procedural and clinical outcome.

scholarly journals Women in surgery: a systematic review of 25 years

BMJ Leader ◽  
2020 ◽  
pp. leader-2019-000199
Author(s):  
Charleen Singh ◽  
Caitlin Loseth ◽  
Noordeen Shoqirat
Keyword(s):  
Quality Of Life ◽  
Systematic Review ◽  
Work Life ◽  
Current Status ◽  
Leadership Roles ◽  
Review Of The Literature ◽  
Life Balance ◽  
Surgical Residency ◽  
Meta Analyses

The number of women entering medicine significantly increased over the last decades. Currently, over half of the medical students are women but less than half are applying to surgery and even less go on to surgical specialties. Even fewer women are seen in leadership roles throughout the profession of surgery and surgical residency. Our purpose of the literature review is to identify any themes, which would provide insight to the current phenomenon. We used the Preferred Reporting Items for Systemic Reviews and Meta-Analyses method for a systematic review of the literature over a 20-year period (1998–2018). Five broad themes were identified: education and recruitment, career development, impact of/on life around the globe and surgical subspecialties as areas of barriers for women entering or considering surgery. The systematic review suggests there are opportunities to improve and encourage women entering the profession of surgery as well as the quality of life for surgeons. Creating systems for mentorship across programmes, having policies to support work–life balance and recognising surgical training overlaps with childbearing years are key opportunities for improvement. Improving the current status in surgery will require direction from leadership.

Tourism research for the GCC region: Current status and future research directions

2021 ◽  
pp. 135481662199996
Author(s):  
Ali Salman Saleh ◽  
Charbel Bassil ◽  
Arsalan Safari
Keyword(s):  
United Arab Emirates ◽  
Current Status ◽  
Future Research ◽  
Research Directions ◽  
Regional Tourism ◽  
Research Theme ◽  
Tourism Sector ◽  
Future Research Directions ◽  
Meta Analyses ◽  
The Impact

Tourism in the Gulf Cooperation Council (GCC) countries has recently been considered by policymakers as a new avenue for economic diversification. Despite the considerable literature concerning the impact of tourism worldwide, only a limited number of studies have looked at the tourism sector in the GCC region or analyzed its economic, sociocultural, and environmental impacts. This article therefore conducts a systematic review of the state of the literature related to tourism in the GCC region. It provides effective insights about the current status, gaps, and challenges and proposes future research directions in this area for academics, practitioners, and policymakers with an interest in regional tourism development. The preferred reporting items for systematic reviews and meta-analyses approach was used to identify and select the papers. Some 23 papers were identified and analyzed. The majority of these studies focused on the United Arab Emirates, specifically the Dubai emirate. We found the most dominant research theme to be tourism planning.

scholarly journals Addition of Androgen-Deprivation Therapy or Brachytherapy Boost to External Beam Radiotherapy for Localized Prostate Cancer: A Network Meta-Analysis of Randomized Trials

2020 ◽  
Vol 38 (26) ◽  
pp. 3024-3031 ◽  
Author(s):  
William C. Jackson ◽  
Holly E. Hartman ◽  
Robert T. Dess ◽  
Sam R. Birer ◽  
Payal D. Soni ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Deprivation Therapy ◽  
Randomized Trials ◽  
Practice Patterns ◽  
Meta Analysis ◽  
External Beam Radiotherapy ◽  
Localized Prostate Cancer ◽  
External Beam ◽  
Brachytherapy Boost ◽  
Meta Analyses

PURPOSE In men with localized prostate cancer, the addition of androgen-deprivation therapy (ADT) or a brachytherapy boost (BT) to external beam radiotherapy (EBRT) have been shown to improve various oncologic end points. Practice patterns indicate that those who receive BT are significantly less likely to receive ADT, and thus we sought to perform a network meta-analysis to compare the predicted outcomes of a randomized trial of EBRT plus ADT versus EBRT plus BT. MATERIALS AND METHODS A systematic review identified published randomized trials comparing EBRT with or without ADT, or EBRT (with or without ADT) with or without BT, that reported on overall survival (OS). Standard fixed-effects meta-analyses were performed for each comparison, and a meta-regression was conducted to adjust for use and duration of ADT. Network meta-analyses were performed to compare EBRT plus ADT versus EBRT plus BT. Bayesian analyses were also performed, and a rank was assigned to each treatment after Markov Chain Monte Carlo analyses to create a surface under the cumulative ranking curve. RESULTS Six trials compared EBRT with or without ADT (n = 4,663), and 3 compared EBRT with or without BT (n = 718). The addition of ADT to EBRT improved OS (hazard ratio [HR], 0.71 [95% CI, 0.62 to 0.81]), whereas the addition of BT did not significantly improve OS (HR, 1.03 [95% CI, 0.78 to 1.36]). In a network meta-analysis, EBRT plus ADT had improved OS compared with EBRT plus BT (HR, 0.68 [95% CI, 0.52 to 0.89]). Bayesian modeling demonstrated an 88% probability that EBRT plus ADT resulted in superior OS compared with EBRT plus BT. CONCLUSION Our findings suggest that current practice patterns of omitting ADT with EBRT plus BT may result in inferior OS compared with EBRT plus ADT in men with intermediate- and high-risk prostate cancer. ADT for these men should remain a critical component of treatment regardless of radiotherapy delivery method until randomized evidence demonstrates otherwise.

scholarly journals Anxiety as a risk factor for cardiovascular disease independent of depression: A narrative review of current status and conflicting findings

2021 ◽  
Vol 8 (1) ◽  
pp. 205510292098746
Author(s):  
Håvard R Karlsen ◽  
Florian Matejschek ◽  
Ingvild Saksvik-Lehouillier ◽  
Eva Langvik
Keyword(s):  
Cardiovascular Disease ◽  
Risk Factor ◽  
Study Design ◽  
Empirical Support ◽  
Narrative Review ◽  
Current Status ◽  
Depression And Anxiety ◽  
Evidential Support ◽  
Meta Analyses

The aim of this paper is to summarise and evaluate the empirical support for the association between anxiety and cardiovascular disease (CVD) and to address challenges related to method and study design. We review results from meta-analyses and more recent findings on the association of anxiety and the risk of CVD. Depression and anxiety are often listed as psychosocial risk markers of CVD, but the role of anxiety as a risk factor for CVD has not received the same evidential support as the effects of depression. Through a narrative review we identified six meta-analyses as well as 15 recent large studies of anxiety and CVD that we summarise. Some of the conflicting findings may be artefacts of study design or population the sample is drawn from. Researchers should take care to be population specific, measurement specific and outcome specific, and to control for comorbid depression.

Open and Endovascular Treatment of Unruptured Carotid-Ophthalmic Aneurysms: Clinical and Radiographic Outcomes

Neurosurgery ◽  
2011 ◽  
Vol 68 (5) ◽  
pp. 1434-1443 ◽  
Author(s):  
Sanjay Yadla ◽  
Peter G. Campbell ◽  
Bartosz Grobelny ◽  
Jack Jallo ◽  
L. Fernando Gonzalez ◽  
...  
Keyword(s):  
Endovascular Treatment ◽  
Combined Treatment ◽  
Combined Modality Treatment ◽  
Endovascular Techniques ◽  
Patient Demographics ◽  
Radiographic Outcomes ◽  
Major Complications ◽  
Initial Procedure ◽  
Elective Setting

Abstract BACKGROUND: Aneurysms of the carotid-ophthalmic artery present unique challenges to cerebrovascular neurosurgeons given their proximity to vital anatomic structures. OBJECTIVE: To report our experience with a combined-modality treatment of unruptured carotid-ophthalmic aneurysms over a 12-year period. METHODS: A retrospective review of 161 patients who underwent open, endovascular, or combined treatment of 170 aneurysms from January 1997 to July 2009 was conducted. Medical records, operative reports, office notes, and follow-up angiograms were reviewed to obtain data on patient demographics, angiographic results, and clinical outcomes. RESULTS: One hundred forty-seven aneurysms were treated via endovascular techniques; 17 aneurysms (10%) were treated with microsurgical clip ligation; and 6 aneurysms (3.5%) were treated with a combined approach. Of the aneurysms treated via an endovascular approach alone, 81.6% of aneurysms had evidence of ≥ 95% occlusion on initial angiogram. There was a 1.4% rate of major complications associated with the initial procedure. Twenty-six of these aneurysms (18.9%) required further intervention on the basis of early angiographic results. Major complications occurred after 6 of 23 open microsurgical procedures (26.1%), including 2 instances of permanent visual loss. Nine clipped patients had long-term angiographic follow-up; none required further intervention. CONCLUSION: Endovascular treatment of carotid-ophthalmic aneurysms with modern endovascular techniques can be performed safely and efficaciously in the elective setting.

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