scholarly journals Prospective study evaluating dynamic changes of cell-free HPV DNA in locoregional viral-associated oropharyngeal cancer treated with induction chemotherapy and response-adaptive treatment

BMC Cancer ◽  
2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Ari J. Rosenberg ◽  
Evgeny Izumchenko ◽  
Alexander Pearson ◽  
Zhen Gooi ◽  
Elizabeth Blair ◽  
...  
Keyword(s):  
Prospective Study ◽  
Treatment Response ◽  
Induction Chemotherapy ◽  
Oropharyngeal Cancer ◽  
Post Treatment ◽  
Smoking History ◽  
Dynamic Changes ◽  
Hpv Dna ◽  
Adaptive Treatment ◽  
Receive Treatment

Abstract Background Human papillomavirus (HPV)-associated oropharyngeal cancer (OPC) has a favorable prognosis which has led to efforts to de-intensify treatment. Response-adaptive de-escalated treatment is promising, however improved biomarkers are needed. Quantitative cell-free HPV-DNA (cfHPV-DNA) in plasma represents an attractive non-invasive biomarker for grading treatment response and post-treatment surveillance. This prospective study evaluates dynamic changes in cfHPV-DNA during induction therapy, definitive (chemo)radiotherapy, and post-treatment surveillance in the context of risk and response-adaptive treatment for HPV + OPC. Methods Patients with locoregional HPV + OPC are stratified into two cohorts: High risk (HR) (T4, N3, $$\ge$$ ≥ 20 pack-year smoking history (PYH), or non-HPV16 subtype); Low risk (LR) (all other patients). All patients receive induction chemotherapy with three cycles of carboplatin and paclitaxel. LR with ≥ 50% response receive treatment on the single-modality arm (minimally-invasive surgery or radiation alone to 50 Gy). HR with ≥ 50% response or LR with ≥ 30% and < 50% response receive treatment on the intermediate de-escalation arm (chemoradiation to 50 Gy with cisplatin). All other patients receive treatment on the regular dose arm with chemoradiation to 70 Gy with concurrent cisplatin. Plasma cfHPV-DNA is assessed during induction, (chemo)radiation, and post-treatment surveillance. The primary endpoint is correlation of quantitative cfHPV-DNA with radiographic response. Discussion A de-escalation treatment paradigm that reduces toxicity without compromising survival outcomes is urgently needed for HPV + OPC. Response to induction chemotherapy is predictive and prognostic and can select candidates for de-escalated definitive therapy. Assessment of quantitative cfHPV-DNA in the context of response-adaptive treatment of represents a promising reliable and convenient biomarker-driven strategy to guide personalized treatment in HPV + OPC. Trial registration This trial is registered with ClinicalTrials.gov on October 1st, 2020 with Identifier: NCT04572100.

Smoking history and PD-1/PDL-1 pathway blockade: Predicting response to treatment in metastatic cancer.

2019 ◽  
Vol 37 (8_suppl) ◽  
pp. 95-95 ◽  
Author(s):  
Caitlin Marie Sullivan ◽  
Jonathan Lu ◽  
John Ross Kucharczyk ◽  
Diana Vesselinovitch ◽  
Neharika Khurana ◽  
...  
Keyword(s):  
Treatment Response ◽  
Smoking Status ◽  
Metastatic Cancer ◽  
Post Treatment ◽  
Inhibitor Therapy ◽  
Response To Treatment ◽  
Smoking History ◽  
Heavy Smoking ◽  
Never Smokers ◽  
Heavy Smokers

95 Background: Identifying patients who will benefit from immune-checkpoint inhibitor therapy is a challenge as proven predicative indicators remain to be elucidated. High tumor mutational burden (TMB) represents a possible biomarker for response to PD1 blockade such as in nivolumab or pembrolizumab. Genomic analyses have shown that patients with heavy smoking history are more likely to have high TMB. However smoking status alone has not been examined independently in relation to treatment response. We sought to determine whether a relationship existed between smoking history and response to treatment in metastatic non-small cell lung cancer (NSCLC), metastatic renal cell carcinoma (mRCC) and metastatic melanoma (mMelanoma). Methods: A retrospective analysis was conducted of Ochsner Health System patients with mRCC, mMelanoma, and NSCLC receiving a minimum of two cycles of nivolumab or pembrolizumab between 12/2014 and 01/2018. Pre- and post-treatment target lesions were analyzed using RECIST criteria to calculate best response to treatment. Patient demographic information was gathered including age, sex, smoking history, and performance status pre and post treatment. Kaplan-Meier method was used to estimate progression free survival (PFS) and overall survival (OS) outcomes. Results: Heavy smokers (>10 pack-years) had a higher response to immunotherapy than light (< 10 years) and never smokers (p = 0.0500). Heavy smokers with NSCLC treated with immuno-therapy also had significantly improved OS compared to light smokers with NSCLC (p=0.003). mRCC immuno-therapy patients with heavy smoking history showed increased PFS compared to light/never smokers (p=0.026). Conclusions: In summary, in response to PD-1 blockade heavy smokers showed improved survival compared to light and never smokers suggesting smoking history may represent a potential predictor of treatment response to PD-1 inhibitor therapy.[Table: see text]

scholarly journals Oral secretory leukocyte protease inhibitor (SLPI): Associations with oropharyngeal cancer and treatment outcome

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0254161
Author(s):  
Brittney L. Dickey ◽  
Bradley Sirak ◽  
Laura Martin-Gomez ◽  
Richard R. Reich ◽  
Martha Abrahamsen ◽  
...  
Keyword(s):  
Protease Inhibitor ◽  
Treatment Response ◽  
Oropharyngeal Cancer ◽  
Secretory Leukocyte Protease Inhibitor ◽  
Response To Treatment ◽  
Hpv Dna ◽  
The Us ◽  
Oral Hpv ◽  
Incomplete Treatment ◽  
Control Study

Background Rates of oropharyngeal cancer (OPC) associated with alcohol & tobacco use have decreased, while human papillomavirus (HPV) associated OPC has increased among men in the US. Secretory leukocyte protease inhibitor (SLPI), detectable in a variety of secretions, has been implicated in cancers of the head and neck, associated with tumor progression and anti-viral activity. Using the recently verified oral gargle specimen, this study aimed to assess the association of salivary SLPI expression with risk of OPC and response to treatment. Methods A case-control study design compared levels of salivary SLPI among OPC cases to age and tobacco smoking matched healthy controls. Oral HPV DNA and SLPI was quantified from oral gargle specimens. Logistic regression estimated odds ratios (OR) and 95% confidence intervals (CI) for associations of oral SLPI and risk of OPC and treatment outcomes. Results In crude and adjusted analyses of 96 OPC cases and 97 age- and smoking-matched controls, OPC was not significantly associated with oral gargle SLPI levels. Among cases, oral SLPI was associated with tonsillectomy (p = 0.018) and among controls oral SLPI was associated with HPV in the oral gargle (p = 0.008). Higher concentrations of SLPI was significantly associated with increased odds of incomplete treatment response (T2: OR: 12.39; 95% CI: 1.44–106.72; T3: OR: 9.86; 95% CI: 1.13–85.90) among all cases, but not among P16+ cases. Conclusions Salivary SLPI was not associated with OPC risk but was associated with higher odds of an incomplete treatment response.

scholarly journals Plasma Circulating Tumor HPV DNA for the Surveillance of Cancer Recurrence in HPV-Associated Oropharyngeal Cancer

2020 ◽  
Vol 38 (10) ◽  
pp. 1050-1058 ◽  
Author(s):  
Bhishamjit S. Chera ◽  
Sunil Kumar ◽  
Colette Shen ◽  
Robert Amdur ◽  
Roi Dagan ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Predictive Value ◽  
Oropharyngeal Cancer ◽  
Treatment Time ◽  
Cancer Recurrence ◽  
Disease Recurrence ◽  
Post Treatment ◽  
Curative Intent ◽  
Hpv Dna ◽  
Blood Tests

PURPOSE Plasma circulating tumor human papillomavirus DNA (ctHPVDNA) is a sensitive and specific biomarker of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). We investigated whether longitudinal monitoring of ctHPVDNA during post-treatment surveillance could accurately detect clinical disease recurrence. METHODS AND MATERIALS A prospective biomarker clinical trial was conducted among patients with nonmetastatic HPV-associated (p16-positive) OPSCC. All patients were treated with curative-intent chemoradiotherapy (CRT). Patients underwent a 3-month post-CRT positron emission tomography/computed tomography scan and were thereafter clinically evaluated every 2-4 months (years 1-2), then every 6 months (years 3-5). Chest imaging was performed every 6 months. Blood specimens were collected every 6-9 months for analysis of plasma ctHPVDNA using a multianalyte digital polymerase chain reaction assay. The primary endpoint was to estimate the negative predictive value (NPV) and positive predictive value (PPV) of ctHPVDNA surveillance. RESULTS One hundred fifteen patients were enrolled, and 1,006 blood samples were analyzed. After a median follow-up time of 23 months (range, 6.1-54.7 months), 15 patients (13%) developed disease recurrence. Eighty-seven patients had undetectable ctHPVDNA at all post-treatment time points, and none developed recurrence (NPV, 100%; 95% CI, 96% to 100%). Twenty-eight patients developed a positive ctHPVDNA during post-treatment surveillance, 15 of whom were diagnosed with biopsy-proven recurrence. Sixteen patients had 2 consecutively positive ctHPVDNA blood tests, 15 of whom developed biopsy-proven recurrence. Two consecutively positive ctHPVDNA blood tests had a PPV of 94% (95% CI, 70% to 99%). Median lead time between ctHPVDNA positivity and biopsy-proven recurrence was 3.9 months (range, 0.37-12.9 months). CONCLUSION Detection of ctHPVDNA in two consecutive plasma samples during post-treatment surveillance has high PPV and NPV for identifying disease recurrence in patients with HPV-associated oropharyngeal cancer and may facilitate earlier initiation of salvage therapy.

scholarly journals Comparison of Selected Immune and Hematological Parameters and Their Impact on Survival in Patients with HPV-Related and HPV-Unrelated Oropharyngeal Cancer

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3256
Author(s):  
Adam Brewczyński ◽  
Beata Jabłońska ◽  
Agnieszka Maria Mazurek ◽  
Jolanta Mrochem-Kwarciak ◽  
Sławomir Mrowiec ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Oropharyngeal Cancer ◽  
Hematological Parameters ◽  
White Blood Cells ◽  
Post Treatment ◽  
Neutrophil Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Hpv Status ◽  
Pre Treatment ◽  
The Impact

Several immune and hematological parameters are associated with survival in patients with oropharyngeal cancer (OPC). The aim of the study was to analyze selected immune and hematological parameters of patients with HPV-related (HPV+) and HPV-unrelated (HPV-) OPC, before and after radiotherapy/chemoradiotherapy (RT/CRT) and to assess the impact of these parameters on survival. One hundred twenty seven patients with HPV+ and HPV− OPC, treated with RT alone or concurrent chemoradiotherapy (CRT), were included. Patients were divided according to HPV status. Confirmation of HPV etiology was obtained from FFPE (Formalin-Fixed, Paraffin-Embedded) tissue samples and/or extracellular circulating HPV DNA was determined. The pre-treatment and post-treatment laboratory blood parameters were compared in both groups. The neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR), and systemic immune inflammation (SII) index were calculated. The impact of these parameters on overall (OS) and disease-free (DFS) survival was analyzed. In HPV+ patients, a high pre-treatment white blood cells (WBC) count (>8.33 /mm3), NLR (>2.13), SII (>448.60) significantly correlated with reduced OS, whereas high NLR (>2.29), SII (>462.58) significantly correlated with reduced DFS. A higher pre-treatment NLR and SII were significant poor prognostic factors for both OS and DFS in the HPV+ group. These associations were not apparent in HPV− patients. There are different pre-treatment and post-treatment immune and hematological prognostic factors for OS and DFS in HPV+ and HPV− patients. The immune ratios could be considered valuable biomarkers for risk stratification and differentiation for HPV− and HPV+ OPC patients.

LI-RADS treatment response algorithm after first-line DEB-TACE: reproducibility and prognostic value at initial post-treatment CT/MRI

2021 ◽  
Author(s):  
Ali Pirasteh ◽  
E. Aleks Sorra ◽  
Hector Marquez ◽  
Robert C. Sibley ◽  
Julia R. Fielding ◽  
...  
Keyword(s):  
Treatment Response ◽  
Prognostic Value ◽  
Post Treatment ◽  
First Line

Treatment response and long-term outcomes in biliary ascariasis: A prospective study

2021 ◽  
Author(s):  
Partha Sarathi Patra ◽  
Abhishek Das ◽  
S.K. Mahiuddin Ahmed ◽  
Souveek Mitra ◽  
Gopal Krishna Dhali
Keyword(s):  
Prospective Study ◽  
Treatment Response ◽  
Long Term Outcomes ◽  
Biliary Ascariasis ◽  
A Prospective Study

scholarly journals Depression treatment response to ketamine: sex-specific role of interleukin-8, but not other inflammatory markers

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jennifer L. Kruse ◽  
Megha M. Vasavada ◽  
Richard Olmstead ◽  
Gerhard Hellemann ◽  
Benjamin Wade ◽  
...  
Keyword(s):  
Treatment Response ◽  
Inflammatory Markers ◽  
Rating Scale ◽  
Antidepressant Medication ◽  
Post Treatment ◽  
Therapeutic Modality ◽  
Depression Treatment ◽  
Open Label ◽  
Time Interaction ◽  
Baseline Levels

AbstractInflammation plays a role in depression pathophysiology and treatment response, with effects varying by sex and therapeutic modality. Lower levels of interleukin(IL)-8 predict depression response to antidepressant medication and to electroconvulsive therapy (ECT), although ECT effects are specific to females. Whether IL-8 predicts depression response to ketamine and in a sex-specific manner is not known. Here, depressed patients (n = 46; female, n = 17) received open label infusion of ketamine (0.5 mg/kg over 40 min; NCT02165449). Plasma levels of IL-8 were evaluated at baseline and post-treatment. Baseline levels of IL-8 had a trending association with response to ketamine, depending upon sex (responder status × sex interaction: p = 0.096), in which lower baseline levels of IL-8 in females (p = 0.095) but not males (p = 0.96) trended with treatment response. Change in levels of IL-8 from baseline to post-treatment differed significantly by responder status (defined as ≥50% reduction in Hamilton Depression Rating Scale [HAM-D] Score), depending upon sex (responder status × sex × time interaction: F(1,42)=6.68, p = 0.01). In addition, change in IL-8 interacted with sex to predict change in HAM-D score (β = -0.63, p = 0.003); increasing IL-8 was associated with decreasing HAM-D score in females (p = 0.08) whereas the inverse was found in males (p = 0.02). Other inflammatory markers (IL-6, IL-10, tumor necrosis factor-α, C-reactive protein) were explored with no significant relationships identified. Given these preliminary findings, further evaluation of sex differences in the relationship between IL-8 and treatment response is warranted to elucidate mechanisms of response and aid in the development of personalized approaches to depression treatment.

scholarly journals Visual Parameters and Retinal Morphology for Polypoidal Choroidal Vasculopathy Pre- and Post-Intravitreal Ranibizumab with or without Photodynamic Therapy: A Short-Term Prospective Study

2021 ◽  
Vol 18 (5) ◽  
pp. 2581
Author(s):  
Rituparna Ghoshal ◽  
Sharanjeet Sharanjeet-Kaur ◽  
Norliza Mohamad Fadzil ◽  
Somnath Ghosh ◽  
Nor Fariza Ngah ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Prospective Study ◽  
Polypoidal Choroidal Vasculopathy ◽  
Reading Speed ◽  
Pigment Epithelium ◽  
Post Treatment ◽  
Base Line ◽  
Intravitreal Ranibizumab ◽  
Pre Treatment ◽  
Choroidal Vasculopathy

The objective of this study was to compare visual parameters and retinal layers’ morphology pre-treatment (baseline) and 6 months post-treatment in polypoidal choroidal vasculopathy (PCV) eyes. A single centre, longitudinal, prospective study was conducted at a public tertiary hospital of Malaysia. Visual parameters including distance and near visual acuity (DVA and NVA), contrast sensitivity (CS), reading speed (RS), and different qualitative and quantitative optical coherence tomography (OCT) parameters were evaluated pre- and 6 months post-treatment. Thirty-three naïve PCV eyes of 32 patients (mean age of 67.62 years) were evaluated pre- and post-treatment of intravitreal ranibizumab with and without photodynamic therapy. After treatment, sub retinal fluid decreased from 27 eyes (84.35%) at baseline to 7 eyes (21.88%) at 6 months while pigment epithelium detachment decreased from 32 eyes (100%) at base line to 15 eyes (46.87%) at 6 months. Mean pre-treatment quantitative morphological OCT retinal parameters including thickness and volume of central sub field, center thickness, center minimum, and maximum thickness reduced significantly. Similarly, all visual parameters including DVA, NVA, CS, and RS showed statistically significant improvement. While 89% of the eyes showed improvement in CS, 78%, 71%, and 65% of the eyes showed improvement in NVA, RS, and DVA, respectively. Thus, CS was the most treatment responsive visual parameter.

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