scholarly journals Evolving Role of Immunotherapy in Recurrent Metastatic Head and Neck Cancer

2020 ◽  
Vol 18 (7) ◽  
pp. 899-906 ◽  
Author(s):  
Xiuning Le ◽  
Renata Ferrarotto ◽  
Trisha Wise-Draper ◽  
Maura Gillison
Keyword(s):  
Overall Survival ◽  
Head And Neck ◽  
Systemic Treatment ◽  
Immune Checkpoint Blockade ◽  
Subsequent Treatment ◽  
First Line ◽  
Improve Response Rate ◽  
The Past ◽  
Important Benefit

Immunotherapy has revolutionized cancer treatment in the past 2 decades, mostly with immune checkpoint blockade approaches. In squamous cell carcinoma of the head and neck (SCCHN), the initial efficacy of immunotherapy was observed in patients with recurrent or metastatic (R/M) disease who received other prior systemic treatment. As monotherapy, anti–PD-1 therapies induce responses in 13% to 18% of patients. More recently, immunotherapy in combination with cytotoxic chemotherapy demonstrated greater safety and efficacy as first-line systemic treatment compared with chemotherapy alone. In R/M SCCHN, the most important benefit of immunotherapy is the significantly improved overall survival, especially in patients with PD-L1–positive tumors. As of 2019, immunotherapy can be used as first-line or subsequent treatment of R/M SCCHN. Many ongoing trials are evaluating immunotherapy combinations or novel immunotherapy strategies, aiming to improve response rate and overall survival. As new targets are identified and new approaches are leveraged, the role of immunotherapy in R/M SCCHN continues to evolve.

scholarly journals Update of Immune Therapies in Recurrent/Metastatic Head and Neck Cancer

2021 ◽  
pp. 297-306
Author(s):  
Danny Rischin
Keyword(s):  
Overall Survival ◽  
Head And Neck ◽  
Standard Of Care ◽  
First Line ◽  
Immune Therapies ◽  
Positive Score ◽  
Previously Treated ◽  
Combined Positive Score ◽  
Overall Survival Benefit

AbstractSince the initial reports of activity of pembrolizumab in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC), investigation of the role of immune therapies has been the major focus of clinical trials in R/M HNSCC. Randomised trials initially with nivolumab and later with pembrolizumab established overall survival benefit in patients with R/M HNSCC previously treated with platinum compared to physicians choice of 2nd line therapy, and have led to regulatory approval around the world. More recently the Keynote-048 trial has compared both pembrolizumab monotherapy and pembrolizumab + platinum/5FU to the Extreme regimen of platinum/5FU/cetuximab in the first-line R/M setting. The key findings from this trial are that pembrolizumab monotherapy compared to Extreme improved overall survival in patients with PD-L1 combined positive score (CPS) ≥ 20 and ≥ 1, and that pembro/chemotherapy improved OS in CPS ≥ 20, CPS ≥ 1 and the total population. Relative to Extreme there was less toxicity in the monotherapy arm and comparable toxicity in the pembro/chemo arm. Based on this trial use of pembrolizumab as part of first-line treatment for R/M HNSCC is appropriate for the majority of patients, and represents a new standard of care. The focus has now moved to identifying combinations that may be superior to pembrolizumab monotherapy or to chemotherapy + pembrolizumab. Some of the more promising approaches under investigation in HNSCC are discussed in this chapter. In summary, immune therapies are now the cornerstone of management of R/M HNSCC with the approval of pembrolizumab in the first-line R/M setting.

scholarly journals Mortality due to cancer treatment delay: systematic review and meta-analysis

BMJ ◽  
2020 ◽  
pp. m4087 ◽  
Author(s):  
Timothy P Hanna ◽  
Will D King ◽  
Stephane Thibodeau ◽  
Matthew Jalink ◽  
Gregory A Paulin ◽  
...  
Keyword(s):  
Systematic Review ◽  
Overall Survival ◽  
Confidence Interval ◽  
Cancer Treatment ◽  
Head And Neck ◽  
Adjuvant Radiotherapy ◽  
Systemic Treatment ◽  
Meta Analysis ◽  
Treatment Delay ◽  
Hazard Ratio

Abstract Objective To quantify the association of cancer treatment delay and mortality for each four week increase in delay to inform cancer treatment pathways. Design Systematic review and meta-analysis. Data sources Published studies in Medline from 1 January 2000 to 10 April 2020. Eligibility criteria for selecting studies Curative, neoadjuvant, and adjuvant indications for surgery, systemic treatment, or radiotherapy for cancers of the bladder, breast, colon, rectum, lung, cervix, and head and neck were included. The main outcome measure was the hazard ratio for overall survival for each four week delay for each indication. Delay was measured from diagnosis to first treatment, or from the completion of one treatment to the start of the next. The primary analysis only included high validity studies controlling for major prognostic factors. Hazard ratios were assumed to be log linear in relation to overall survival and were converted to an effect for each four week delay. Pooled effects were estimated using DerSimonian and Laird random effect models. Results The review included 34 studies for 17 indications (n=1 272 681 patients). No high validity data were found for five of the radiotherapy indications or for cervical cancer surgery. The association between delay and increased mortality was significant (P<0.05) for 13 of 17 indications. Surgery findings were consistent, with a mortality risk for each four week delay of 1.06-1.08 (eg, colectomy 1.06, 95% confidence interval 1.01 to 1.12; breast surgery 1.08, 1.03 to 1.13). Estimates for systemic treatment varied (hazard ratio range 1.01-1.28). Radiotherapy estimates were for radical radiotherapy for head and neck cancer (hazard ratio 1.09, 95% confidence interval 1.05 to 1.14), adjuvant radiotherapy after breast conserving surgery (0.98, 0.88 to 1.09), and cervix cancer adjuvant radiotherapy (1.23, 1.00 to 1.50). A sensitivity analysis of studies that had been excluded because of lack of information on comorbidities or functional status did not change the findings. Conclusions Cancer treatment delay is a problem in health systems worldwide. The impact of delay on mortality can now be quantified for prioritisation and modelling. Even a four week delay of cancer treatment is associated with increased mortality across surgical, systemic treatment, and radiotherapy indications for seven cancers. Policies focused on minimising system level delays to cancer treatment initiation could improve population level survival outcomes.

scholarly journals Circulating MicroRNAs as Prognostic Molecular Biomarkers in Human Head and Neck Cancer: A Systematic Review and Meta-Analysis

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Shree Ram Lamichhane ◽  
Thanuja Thachil ◽  
Harriet Gee ◽  
Natalie Milic
Keyword(s):  
Systematic Review ◽  
Overall Survival ◽  
Head And Neck Cancer ◽  
Head And Neck ◽  
Cancer Patients ◽  
Neck Cancer ◽  
Meta Analysis ◽  
Prognostic Role ◽  
Circulating Micrornas

Background. Circulating microRNAs (miRNAs) are potential molecular biomarkers for cancer detection; however, little is known about their prognostic role in head and neck cancer. This current study is aimed at evaluating the role of novel miRNAs in the survival of head and neck cancer patients. Materials and Methods. We performed a systematic literature search using online databases for articles published between December 2006 and February 2019. A meta-analysis was conducted to assess the correlation between miRNA expressions and overall survival (OS) among the selected head and neck cancer studies. After multilevel screening by reviewers, meta-analysis was performed using hazard ratios (HR) and associated 95% confidence interval (CI) of survival to calculate a pooled effect size. Result. A total of 1577 patients across 13 studies were included in the literature review, with 18 miRNAs upregulated and 4 miRNAs downregulated predicting a poor overall survival. The forest plot generated using cumulated survival data resulted in a pooled HR value of 2.943 (95% CI: 2.394-3.618) indicating a strong association of dysregulated miRNA expression with a poor outcome. Only 2 miRNAs—low levels of miR-9 and high levels of miR-483-5p—were observed in two studies, both showing a significant association with overall cancer survival. Conclusion. To our knowledge, this is the first comprehensive systematic review and meta-analysis that examines the prognostic role of circulating miRNAs from blood in head and neck cancer patients. The combined effect estimates a HR across multiple studies and also supports the previous individual findings that an alteration in miRNA expression is highly associated with poor prognosis. This has the potential to use serum and/or plasma miRNAs as biomarkers and become novel tools for predicting the prognosis of head and neck cancer patients in the near future.

Evolving Therapeutic Strategies in Mucosal Melanoma Have Not Improved Survival over Five Decades

2016 ◽  
Vol 82 (1) ◽  
pp. 1-5 ◽  
Author(s):  
Daniel D. Kirchoff ◽  
Gary B. Deutsch ◽  
Leland J. Foshag ◽  
Ji Hey Lee ◽  
Myung-Shin Sim ◽  
...  
Keyword(s):  
Overall Survival ◽  
Adjuvant Therapy ◽  
Mucosal Melanoma ◽  
Surgical Interventions ◽  
Entire Cohort ◽  
The Past ◽  
Survival Difference ◽  
Disease Site ◽  
The Ideal

Mucosal melanoma represents a distinct minority of disease sites and portends a worse outcome. The ideal treatment and role of adjuvant therapy remains unknown at this time. We hypothesized that a combination of neoadjuvant and adjuvant therapies would improve survival in these aggressive melanomas. Our large, prospectively maintained melanoma database was queried for all patients diagnosed with mucosal melanoma. Over the past five decades, 227 patients were treated for mucosal melanoma. There were 82 patients with anorectal, 75 with sinonasal, and 70 with urogenital melanoma. Five-year overall survival and melanoma-specific survival for the entire cohort were 32.8 and 37.5 per cent, respectively, with median overall survival of 38.7 months. One hundred forty-two patients (63.8%) underwent adjuvant therapy and 15 were treated neo-adjuvantly (6.6%). There was no survival difference by therapy type or timing, disease site, or decade of diagnosis. There was improved survival in patients undergoing multiple surgeries (Hazard Ratio [HR] 0.55, P = 0.0005). Patients receiving neoadjuvant therapy had significantly worse survival outcomes (HR 2.49, P = 0.013). Over the past five decades, improvements have not been seen in outcomes for mucosal melanoma. Although multiple surgical interventions portend a better outcome in patients with mucosal melanoma, adjuvant treatment decisions must be individualized.

Role of silicon under water deficit stress in wheat: (Biochemical perspective): A review

2016 ◽  
Vol 37 (2) ◽  
Author(s):  
Sarang S. Sapre ◽  
Dinesh N. Vakharia
Keyword(s):  
Oxidative Stress ◽  
Water Deficit ◽  
Stress Factors ◽  
Water Deficit Stress ◽  
First Line ◽  
The Past ◽  
Rapid Absorption ◽  
Microscopic Studies ◽  
Stress Application

Silicon’s role in mediating resistance against various stresses has been a matter of focus in the past decade. Poaeceae family plants are known as high accumulators of silicon. Wheat shows rapid absorption, the optimum accumulation of silicon occurring at around 20 days. Silicon plays a role as a mechanical and a physiological barrier. It also alters the levels of osmolytes and antioxidant enzymes which are a first line of defense in the water deficit stress; also reducing the levels of oxidative stress factors such as hydrogen peroxide. But the results vary with respect to the modes of stress application and its duration. Nowadays, foliar mode of silicon application is carried out compared to the traditional soil application yielding some promising results. Further studies are needed to confirm the mechanisms governing protection which can be done with the comparison of the transcriptome analysis of the stressed plants and also microscopic studies revealing the site of deposition.

scholarly journals Single Centre Experience of Managing Patients with Double Hit Lymphoma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5868-5868
Author(s):  
Shankaranarayana Paneesha ◽  
Iman Qureshi ◽  
Malahat Saeed ◽  
Richard Lovell ◽  
Emmanouil Nikolousis ◽  
...  
Keyword(s):  
Overall Survival ◽  
Complete Remission ◽  
Progressive Disease ◽  
Salvage Chemotherapy ◽  
Line Treatment ◽  
First Line ◽  
Single Centre ◽  
Single Centre Experience ◽  
First Line Treatment

Abstract Double or triple hit Lymphomas (DHL) are characterized by translocation rearrangements of C-MYC with the addition of BCL2 and/or BCL 6, which are associated with a poor outcome due to their genetic complexity . Clinical controversies remain regarding the optimum treatment for patients with DHL due to lack of consensus regarding the optimal management and also age and frailty being a significant obstacle, limiting the role of dose-escalated or intensified therapy. Literature review suggests overall median survival for DHL patients is from 0.2-1.5years2. We report our single centre experience of treating this patient group. Materials & Methods: This single centre retrospective study evaluated the outcome of DHL patients who underwent various lines of treatment including standard R-CHOP chemotherapy, more intensive chemotherapy regimens and allogeneic stem cell transplantation (AlloSCT). Diagnosis of DHL was as per the 2008 WHO classification. Statistical analysis was performed by using SPSS 23®. Results: Our study included fourteen patients (9M; 5F) with a median age 60.5 years (range 33-65). 4 patients had stage 2B disease, 3 had stage 3B and 7 had 4B disease. R-CHOP chemotherapy only was commenced as first line treatment in 4 patients, R-CHOP plus intrathecal chemotherapy was given to 2 patients and 1 patient received R-CEOP. 5 patients received intensive chemotherapy with R-CODOX-M/R-IVAC where as one patient received EPOCH in a different centre prior to transfer. 1 patient received radiotherapy only. 10 patients were in complete remission following first line chemotherapy. One patient progressed following first line treatment and was managed palliatively. One patient relapsed whilst awaiting AlloSCT and was given mini-DEX BEAM salvage chemotherapy prior to transplant. One patient had a partial response to first line treatment and was given further rituximab but had progressive disease and was also managed palliatively. One patient had progressive disease and received GDP chemotherapy. 8 patients underwent AlloSCT with BEAM Alemtuzumab conditioning with cyclosporine as GvHD prophylaxis (6 unrelated and 2 sibling donors). The mean overall survival from starting treatment for DHL for the non-transplant cohort was 18.5 months (Range: 0.5 to 36.5) and the median OS was 8.3 months (Range: 4 to 12.6) as compared to mean overall survival of 44.2 months (Range: 22.2 to 66.35) in the transplant cohort with median overall survival not reached (p value: 0.46, Log Rank). In our patients, there was no progression after 3 months from Allo SCT. One patient progressed 6 weeks and died 8 weeks post AlloSCT, whereas two patients progressed 12 weeks and died 14 weeks post AlloSCT. In the cohort who did not undergo AlloSCT, 3 patients have died and two remain in complete remission and 1 patient is undergoing salvage chemotherapy for refractory disease. Conclusion: Our single centre experience of limited number of patients with DHL suggests AlloSCT as a consolidative treatment in first complete remission, may offer survival benefit as compared to no consolidation. Our data also shows no progression of DHL 3 months post AlloSCT highlighting the potential graft versus lymphoma effect. This requires further evaluation in a larger cohort to confirm our preliminary findings and identify potential biomarkers of best response. Confirmation of this result in larger cohort will identify the role of AlloSCT in DHL and enable to reach consensus in the DHL management. Disclosures Kishore: celgene: Other: travel grant.

scholarly journals Impact of New Chemotherapy Regimens on the Treatment Landscape and Survival of Locally Advanced and Metastatic Pancreatic Cancer Patients

2020 ◽  
Vol 9 (3) ◽  
pp. 648 ◽  
Author(s):  
Markus Kieler ◽  
Matthias Unseld ◽  
Daniela Bianconi ◽  
Martin Schindl ◽  
Gabriela V. Kornek ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Median Overall Survival ◽  
Systemic Treatment ◽  
Locally Advanced ◽  
Survival Rates ◽  
Cox Proportional Hazards Model ◽  
Metastatic Pancreatic Cancer ◽  
Line Treatment ◽  
First Line

Background: New chemotherapy regimens for the treatment of metastatic pancreatic cancer have changed the therapy paradigm. We aimed to assess their impact on the treatment landscape and clinical outcome at our academic institution. Methods: In this single institutional posthoc registry analysis, we assessed characteristics and survival rates from all patients with locally advanced and metastatic pancreatic cancer who started a systemic treatment between 01/2011 and 12/2017. Survival analyses were performed by Kaplan-Meier and Cox proportional hazards model. Results: A total of 301 patients started a systemic treatment in the observation period. In the first line treatment, we observed a shift from the four different main regimens (gemcitabine/nab-paclitaxel, modified FOLFIRINOX, gemcitabine/oxaliplatin +/− erlotinib or gemcitabine alone) to gemcitabine/nab-paclitaxel and modified FOLFIRINOX that add up to more than 80% of administered first line treatments in each of the time cohorts (2011–2013 vs. 2014–2017). The rate for first line modified FOLFIRINOX treatment was balanced between the two groups (19% and 15%). Median overall survival differed significantly between the two time cohorts (8.89 versus 11.9 months, p = 0.035). Survival rates for different first to second line treatment sequences (modified FOLFIRINOX to gemcitabine/nab-paclitaxel, gemcitabine/nab-paclitaxel to fluoropyrimidines plus nanoliposomal irinotecan, or gemcitabine/nab-paclitaxel to fluoropyrimidines plus oxaliplatin) were not significantly different and median overall survival ranged from 14.27 to 15.64 months. Conclusion: Our study provides real-world evidence for the effectiveness of the new chemotherapy regimens and underscores the importance of the choice of the front-line regimen when considering different sequencing strategies.

Prognostic role of inflammatory index in head and neck squamous-cell carcinoma patients in first line chemotherapy.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. e18054-e18054
Author(s):  
Valentina Fausti ◽  
Federica Recine ◽  
Flavia Foca ◽  
Sebastiano Calpona ◽  
Davide Bruschi ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Neck Squamous Cell Carcinoma ◽  
Prognostic Role ◽  
First Line ◽  
Inflammatory Index ◽  
Line Chemotherapy

Basic Overview of Current Immunotherapy Approaches in Cancer

2016 ◽  
pp. 298-308 ◽  
Author(s):  
Vamsidhar Velcheti ◽  
Kurt Schalper
Keyword(s):  
Immune Evasion ◽  
Immune Checkpoint ◽  
Immune Checkpoint Blockade ◽  
Therapeutic Strategies ◽  
Checkpoint Blockade ◽  
Basic Principles ◽  
The Past ◽  
Recent Success

Recent success of immunotherapy strategies such as immune checkpoint blockade in several malignancies has established the role of immunotherapy in the treatment of cancer. Cancers use multiple mechanisms to co-opt the host-tumor immune interactions, leading to immune evasion. Our understanding of the host-tumor interactions has evolved over the past few years and led to various promising new therapeutic strategies. This article will focus on the basic principles of immunotherapy, novel pathways/agents, and combinatorial immunotherapies.

Detection of Gastroesophageal Reflux in the Head and Neck: The Role of Scintigraphy

1989 ◽  
Vol 98 (1) ◽  
pp. 74-80 ◽  
Author(s):  
Daniel B. Kuriloff ◽  
Richard Goldfarb ◽  
Paul Chodosh ◽  
Fukiat Ongseng
Keyword(s):  
Gastroesophageal Reflux ◽  
Head And Neck ◽  
Diagnostic Tests ◽  
Upper Airway ◽  
Noninvasive Method ◽  
Sulfur Colloid ◽  
The Past ◽  
Diagnostic Modalities

Patients with gastroesophageal reflux (GER) present to the head and neck specialist with a myriad of nonspecific complaints that may be manifestations of pharyngoesophageal or upper airway involvement. Numerous diagnostic tests for GER have been used in the past with varying success. In the present study, gastroesophageal scintigraphy using 99 mtechnetium-sulfur colloid was used to evaluate 28 patients with head and neck manifestations of GER. The role of gastroesophageal scintigraphy as an accurate and noninvasive method of detecting GER is discussed in the context of other current diagnostic modalities.

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