The Past: What We Have Learned in the Last Decade

AbstractHodgkin lymphoma (HL) has become a curable malignancy for most patients during the last decades. However, many controversies still exist on the optimal strategy of how to cure our patients. The key question is how to balance the risks and toxicities of chemotherapy and radiotherapy against the need for a definite treatment for early or advanced-stage HL patients. However, although many studies have been conducted and reported during the past decade, interpretation of their results and treatment recommendations might vary significantly in different countries. For example, early-stage HL might be divided into two different subgroups: early favorable and early unfavorable or not. Treatment of early-stage HL might include radiotherapy (“combined modality”) or not. Depending on the extent of radiotherapy, the schedule and number of chemotherapy cycles are also questioned. For advanced-stage HL, the situation is not much different. Compared with ABVD (adriamycin, bleomycin, vinblastine, and dacarbazine), the more aggressive escalated BEACOPP regimen (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone) is highly effective, but also raises concern due to excessive toxicity. Thus, there is a controversy about the standard of care for advanced HL patients. Because no mature results comparing these approaches with each other are currently available, it remains our duty to share the preliminary information with our patients and to figure out the most appropriate individual treatment strategy. Of course, the discussion of these issues is influenced by experiences and preferences. In contrast, in this article, we will try to focus on the available scientific evidence regarding the first-line treatment of HL. Of course, focusing on the last decade necessarily exclude the most recent results from ongoing studies. Thus, even though this article comprises treatment recommendations for HL patients, the best treatment certainly still is within properly designed prospective clinical trials.

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Difficult-to-treat gout flares: eligibility for interleukin-1 inhibition in private practice is uncommon according to current EMA approval

Rheumatology ◽

10.1093/rheumatology/kez203 ◽

2019 ◽

Vol 58 (12) ◽

pp. 2181-2187 ◽

Cited By ~ 6

Author(s):

Tristan Pascart ◽

Laurène Norberciak ◽

Hang-Korng Ea ◽

Sahara Graf ◽

Pascal Guggenbuhl ◽

...

Keyword(s):

Interleukin 1 ◽

Standard Of Care ◽

Acute Gout ◽

Second Line ◽

First Line ◽

Cross Sectional ◽

The Past ◽

Systemic Glucocorticoids ◽

Anti Inflammatory ◽

Gout Flares

Abstract Objective The objective was to determine the proportion of patients with difficult-to-treat or difficult-to-prevent acute gout attacks eligible for IL-1 inhibition. Methods Participants included in the French cross-sectional GOSPEL cohort (n = 1003 gout patients) were examined for contraindications and intolerance to standard of care (SoC) drugs of gout flares (colchicine, non-steroidal anti-inflammatory drugs and systemic glucocorticoids). Patients were classified as definitely eligible for first-line IL-1 inhibition (canakinumab) according to European summary of product characteristics (contraindications/intolerance to SoC and at least three flares per year) without any other anti-inflammatory options (contraindications/intolerance only), or potentially eligible (precaution of use). Eligibility to receive IL-1 during an on-going flare related to insufficient efficacy was assessed (second-line eligibility). Results Definite first-line eligibility for IL-1 therapy was found in 10 patients (1%) and contraindication to all SoC therapies in nine patients who had presented <3 flares in the past 12 months. At least precaution of use for SoC therapies was noted for 218/1003 patients (21.7%). Of 487 patients experiencing flares at baseline, 114 (23.4%) were still experiencing pain scored ⩾4/10 numeric scale on day 3, one of whom could not receive further SoC drugs. Only nine of them had three or more flares in the past year and were eligible for second-line IL-1 inhibition. Conclusion Despite significant numbers of patients without any SoC anti-inflammatory therapeutic options for gout flares, eligibility for IL-1 inhibition therapy according to current European approval is rare.

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Optimizing First-Line Therapy for Follicular Lymphoma: Is It Time for Chemotherapy-Free Approaches?

Journal of the National Comprehensive Cancer Network ◽

10.6004/jnccn.2019.5038 ◽

2019 ◽

Vol 17 (11.5) ◽

pp. 1414-1416

Author(s):

Richard I. Fisher

Keyword(s):

Follicular Lymphoma ◽

Standard Of Care ◽

Hematologic Malignancies ◽

First Line ◽

Current Standard ◽

The Past ◽

First Line Therapy ◽

Free Treatment ◽

Tremendous Progress ◽

Made In

Over the past several decades, tremendous progress has been made in the treatment of follicular lymphoma. The addition of rituximab to chemotherapy led to significant improvements in survival in the 1990s. Current standard of care in advanced-stage, previously untreated follicular lymphoma is rituximab plus chemotherapy, sometimes followed by rituximab maintenance. Now, as more research is conducted in the field of chemotherapy-free treatment, Dr. Richard I. Fisher discussed the importance of carefully constructed phase II or III trials at the NCCN 2019 Annual Congress: Hematologic Malignancies. He maintained that a nonchemotherapy treatment regimen comprising rituximab + lenalidomide can be considered in carefully selected patients, and that it is currently the only chemotherapy-free treatment that should be recommended.

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Update on Intra-Arterial Chemotherapy for Retinoblastoma

The Scientific World JOURNAL ◽

10.1155/2014/869604 ◽

2014 ◽

Vol 2014 ◽

pp. 1-6 ◽

Cited By ~ 11

Author(s):

Mario Zanaty ◽

Guilherme Barros ◽

Nohra Chalouhi ◽

Robert M. Starke ◽

Philip Manasseh ◽

...

Keyword(s):

Advanced Stage ◽

High Efficacy ◽

First Line ◽

Intravenous Chemotherapy ◽

Technical Aspects ◽

The Past

The tools for managing retinoblastoma have been increasing in the past decade. While globe-salvage still relies heavily on intravenous chemotherapy, tumors in advanced stage that failed chemotherapy are now referred for intra-arterial chemotherapy (IAC) to avoid enucleation. However, IAC still has many obstacles to overcome. We present an update on the indications, complications, limitations, success, and technical aspects of IAC. Given its safety and high efficacy, it is expected that IAC will replace conventional strategies and will become a first-line option even for tumors that are amenable for other strategies.

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Population-Based, Cause-Specific Risk of Non-Lymphoma Deaths Among 20,491 Adults with Classical Hodgkin Lymphoma (cHL) Treated with Initial Chemotherapy in the United States, 2000-2015

Blood ◽

10.1182/blood-2019-124831 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 4034-4034

Author(s):

Graca M. Dores ◽

Rochelle E. Curtis ◽

Nicole H. Dalal ◽

Martha S. Linet ◽

Lindsay M. Morton

Keyword(s):

Adverse Events ◽

Early Stage ◽

The United States ◽

First Year ◽

Advanced Stage ◽

Treatment Approaches ◽

The Past ◽

Specific Risk ◽

Stage Disease

Introduction: Advances in cHL treatment over the past 50 years have been fueled, in part, by recognition of long-term treatment-related complications that emerged after cure of cHL became a reality. While cHL-specific survival has continued to improve with time, premature death following diagnosis and treatment of cHL remains life-limiting. Most studies of cHL mortality have focused on long-term survivors and included patients treated with chemotherapy approaches and radiation techniques used in the past. Therefore, we sought to comprehensively quantify early and late cause-specific risks of death among U.S. adults with cHL treated with chemotherapy during a treatment era predominated by ABVD-based (doxorubicin, bleomycin, vinblastine, dacarbazine) chemotherapy. Methods: We used data from 17 cancer registry areas of the Surveillance, Epidemiology, and End Results Program to quantify risks of death among individuals diagnosed with early (I/II) or advanced (III/IV) stage cHL between ages 20-74 years and treated with initial chemotherapy during 2000-2015. We calculated standardized mortality ratios (SMRs) and 95% confidence intervals to compare cause-specific risk of death following cHL to that expected in the general U.S. population and estimated absolute excess risks (per 10,000 patient-years) to quantify disease-specific death burden. Results: Among 24,205 cHL patients, we assessed mortality among the 85% (n=20,491) treated with initial chemotherapy (37% of the 20,491 also received initial radiotherapy). With a mean follow-up of 6.7 years, we observed 3,230 deaths due to lymphoma (n=1,936), other neoplasms (n=273), noncancers (n=937), and unknown (n=84) causes. The risk of non-lymphoma deaths overall was significantly elevated 1.5- and 2.3-fold among adults diagnosed with early or advanced cHL, respectively, representing 20 (early stage) and 75 (advanced stage) excess deaths/10,000 patient-years. The most common causes of noncancer deaths were attributed to cardiovascular (n=284), respiratory (n=166), and infectious (n=119) diseases and accidents/falls/adverse events (n=121). The greatest increased risk of cardiovascular deaths was observed for heart disease <1-year after cHL which persisted 1-4 and >5 years after early and advanced stage cHL. Death from interstitial lung disease (ILD) significantly exceeded the expected rate by 14- and 24-fold in early and advanced stage cHL, respectively, most notably within the first year of diagnosis (SMRearly=90; SMRadvanced=128), with SMRs decreasing substantially after 1-year but remaining significantly increased in both stage groups. Patients were also prone to infection-related deaths irrespective of early (SMRearly=2.2) or advanced (SMRadvanced=3.9) cHL, both <1 or >1 year after diagnosis, with the greatest excesses occurring within the first year. Individuals with early (SMRearly=1.8) and advanced stage (SMRadvanced=4.2) disease had significantly elevated risks of death from adverse events (deaths coded as sequelae of drug, treatment, or other specified exposure), most notably <1 year after cHL diagnosis (SMRearly=7.5; SMRadvanced=17.5). Among non-lymphoma neoplasms, death from myelodysplastic syndromes/acute myeloid leukemia (MDS/AML) was significantly increased among early (SMRearly=5.2) and advanced stage (SMRadvanced=8.6) cHL. No MDS/AML deaths occurred within 1-year of cHL, but risks increased to >9-fold among both stage groups 1-4 years after diagnosis, and excesses persisted at >5-years among those with advanced stage cHL (SMRadvanced=9.1). Lung cancer accounted for the majority of solid tumor deaths among those with early (SMRearly=1.4) and advanced stage (SMRadvanced=1.9) cHL, with heightened risks beginning at >5 years among early stage cHL and at 1-4 years among advanced stage disease. Conclusion: Despite tailored treatment approaches in an ABVD-predominant era, risk of non-lymphoma deaths remains significantly elevated among cHL patients 20-74 years of age in the U.S., with early or advanced stage disease, and <1 or >1 year from diagnosis. Our data strongly support implementation of preventive and supportive measures following cHL diagnosis and continued refinement of treatment approaches to minimize premature deaths. Disclosures No relevant conflicts of interest to declare.

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Retrast: Retreatment after adjuvant trastuzumab—Our regional southern Italy experience.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e11526 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e11526-e11526

Author(s):

Michele Caruso ◽

Vincenzo Adamo ◽

Paolo Tralongo ◽

Dario Giuffrida ◽

Vittorio Gebbia ◽

...

Keyword(s):

Median Time ◽

Early Stage ◽

Rare Event ◽

Standard Of Care ◽

First Line ◽

Primary Resistance ◽

Adjuvant Trastuzumab ◽

First Line Therapy ◽

Line Of Therapy ◽

Metastatic Sites

e11526 Background: Trastuzumab (T) is the standard of care for pts with HER2+ve BC. Relapse after adj T remains a rare event. Since the large use of T in adj setting, becomes crucial to evaluate advantages of retreatment with T for pts who relapsed after treatment in early stage. There is still lack of clinical evidence and poor data from CT to say that there is a benefit in T re-exposure after relapse following adj T. Methods: Since Jun 2006 and Dec 2011, we reviewed pts with early BC treated with T in adj therapy, relapsed and re-treated with T in first line therapy, in 10 departments of medical oncology in Sicily. We aimed to study feasibility, responses and treatment outcome. Results: 62 pts with HER2+ve fulfilled the criteria for this analysis and 47 were evaluated. Pts had a median age of 53 ys (29-79). ER/PgR-ve cases were 16 (34 %). Ki67 was > 20% in 34 pts (74%). 31 pts (64%) had >3 nodes+ve. All the pts received adj therapy with anthra+/-taxane. 55% of pts had >2 metastatic sites. 12 (25,5%) pts were revalued for HER2: 10 pts confirmed 3+ and two pts 2+ were FISH+. Median time from diagnosis to relapse was 25 mos (7 – 36). Median time from last dose of T to relapse was 10 ms (2 – 35). 33 (70,2%) pts and 14 pts (29,8%) had early (< 12 ms) and late progression (≥ 12 ms) respectively after adj T. First line of therapy was T in combination with mono/polychemotherapy in 42 pts (89,3%) and 5 pts (10,6%) respectively. 27 pts (57,4%) had objective responses (CR 5, PR 22) and 7 pts (14,8%) stable disease. 13 pts (27,6%) had progression: all of these pts had early progressive disease after adj T, 9 pts (69,2%) had Ki67>20%, 5 pts (38,4%) were ER/PgR-ve and 8 pts (61,5%) ER/PgR+ve. Median TTP was 4 mos (range 2-7). Median TTP for early and late relapses pts were respectively 3,7 and 4,8 mos, (p = 0,4). Median OS from relapse to death was 23 mos (r 12 – 37). LVSD G1 (EF < 60-50%) was observed only in 7 pts (14%). Conclusions: Our data confirm the feasibility and safety of treatment with T after adj T therapy and is active for a disease control rate in 72,4% of cases. These results demonstrate that relapses after adj T occurred early (<12 ms) in 70% of pts. However pts with primary resistance (27,6%) should be well categorized using biomolecular markers to receive up-front drugs that overcome the resistance to T.

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How to Choose the Best Cross-linking Procedure in 2016

European Ophthalmic Review ◽

10.17925/eor.2015.09.02.98 ◽

2015 ◽

Vol 09 (02) ◽

pp. 98

Author(s):

Nikki Hafezi ◽

◽

Farhad Hafezi ◽

◽

...

Keyword(s):

Solid Body ◽

Research Evidence ◽

Scientific Evidence ◽

Standard Of Care ◽

Cross Linking ◽

Common Pathway ◽

Corneal Ectasia ◽

The Past ◽

Final Common Pathway

Ever since cross-linking (CXL) technology was introduced into clinical ophthalmology in 1999, the technique has established itself as a standard of care in the treatment of corneal ectasia. The original protocol, referred to as the ‘Dresden protocol’, consisted of 30 minutes of iso-osmolaric riboflavin instillation on a de-epithelialised cornea, followed by irradiation at 365 nm and 3 mW/cm2for 30 minutes. These settings correspond to a fluence of 5.4 J/cm2. A large variety of modifications of this original protocol have emerged in the past years: some of these modifications are backed up by a solid body of research evidence, both clinically and experimentally, whereas other modifications are based on little to no scientific evidence. Navigating through this ‘sea of new protocols’ is becoming increasingly difficult for the treating ophthalmologist. The two most important modifications are transepithelial (epi-on) CXL and accelerated CXL. Most interestingly, they seem to share a final common pathway, which determines efficacy: oxygen dependency.

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Evolving Strategies in First-Line Chronic Lymphocytic Leukemia: Is There a Role for Chemoimmunotherapy?

Journal of the National Comprehensive Cancer Network ◽

10.6004/jnccn.2019.5026 ◽

2019 ◽

Vol 17 (11.5) ◽

pp. 1408-1410 ◽

Cited By ~ 1

Author(s):

Jennifer R. Brown ◽

William G. Wierda

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Standard Of Care ◽

Hematologic Malignancies ◽

Lymphocytic Leukemia ◽

New Drugs ◽

First Line ◽

The Past ◽

Annual Congress ◽

Line Setting ◽

Made In

With the enormous progress made in treatment and management, many oncologists have called this the golden age of chronic lymphocytic leukemia (CLL). The past few years alone have seen the approval of multiple agents, including small molecule inhibitors that have led to longer, more durable periods of disease control. However, the introduction of these new drugs into the armamentarium has raised an important question regarding standard of care: is there still a role for chemoimmunotherapy in the first-line setting? At the NCCN 2019 Annual Congress: Hematologic Malignancies, Drs. William G. Wierda and Jennifer R. Brown presented opposing sides of the debate.

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Efficacy and safety results from AvaALL: an open-label, randomized phase III trial of standard of care (SOC) with or without continuous bevacizumab (Bev) treatment beyond progression (PD) in patients (pts) with advanced non-small-cell lung cancer (NSCLC) progressing after first-line Bev and chemotherapy (chemo)

Pneumologie ◽

10.1055/s-0037-1619221 ◽

2018 ◽

Vol 72 (S 01) ◽

pp. S39-S40

Author(s):

F Griesinger ◽

J Bennouna ◽

J de Castro Carpeno ◽

AM Dingemans ◽

F Grossi ◽

...

Keyword(s):

Lung Cancer ◽

Standard Of Care ◽

Small Cell ◽

Phase Iii ◽

Efficacy And Safety ◽

Small Cell Lung ◽

First Line ◽

Open Label ◽

Phase Iii Trial ◽

Treatment Beyond Progression

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Risk Factor Of Substitution ARV First Line People Living With HIV/AIDS In General Hospital Buleleng Bali

STRADA JURNAL ILMIAH KESEHATAN ◽

10.30994/sjik.v9i1.240 ◽

2020 ◽

Vol 9 (1) ◽

pp. 190-197

Author(s):

Luh Putu Desy Puspaningrat ◽

Gusti Putu Candra ◽

Putu Dian Prima Kusuma Dewi ◽

I Made Sundayana ◽

Indrie Lutfiana

Keyword(s):

Risk Factor ◽

General Hospital ◽

Medical Records ◽

Secondary Data ◽

District General Hospital ◽

People Living With Hiv ◽

First Line ◽

The Past ◽

Factor Substitution ◽

Living With Hiv

Substitution is still a threat to the failure of ARV therapy so that no matter how small it must be noted and monitored in ARV therapy. The aims was analysis risk factor substitution ARV first line in therapy ARV. This study was an analytic longitudinal study with retrospective secondary data analysis in a cohort of patients receiving ARV therapy at the District General Hospital of Buleleng District for the period of 2006-2015 and secondary data from medical records of PLHA patients receiving ART. Result in this study that the percentage of first-line ARV substitution events is 9.88% (119/1204) who received ARV therapy for the past 11 years. Risk factors that increase the risk of substitution in ARV therapy patients are zidovudine (aOR 4.29 CI 1.31 -2.65 p 0.01), nevirapine (aOR1.86 CI 2.15 - 8.59 p 0.01) and functional working status (aOR 1.46 CI 1.13 - 1.98 p 0.01).

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