The efficacy of immunotherapy targeting the PD-1/PD-L1 pathway has previously been demonstrated in metastatic head and neck squamous cell carcinoma (HNSCC). Stereotactic Body Radiotherapy (SBRT) aims ...at ablating metastatic lesions and may play a synergistic role with immunotherapy. The purpose of this study is to assess the safety and efficacy of triple treatment combination (TTC) consisting of the administration of durvalumab and tremelimumab in combination with SBRT in metastatic HNSCC.
This is a phase I/II single arm study that will include 35 patients with 2-10 extracranial metastatic lesions. Patients will receive durvalumab (1500 mg IV every 4 weeks (Q4W)) and tremelimumab (75 mg IV Q4W for a total of 4 doses) until progression, unacceptable toxicity or patient withdrawal. SBRT to 2-5 metastases will be administered between cycles 2 and 3 of immunotherapy. The safety of the treatment combination will be evaluated through assessment of TTC-related toxicities, defined as grade 3-5 toxicities based on Common Terminology Criteria for Adverse Events (v 4.03), occurring within 6 weeks from SBRT start, and that are definitely, probably or possibly related to the combination of all treatments. We hypothesize that dual targeting of PD-L1 and CTLA-4 pathways combined with SBRT will lead to < 35% grade 3-5 acute toxicities related to TTC. Progression free survival (PFS) will be the primary endpoint of the phase II portion of this study and will be assessed with radiological exams every 8 weeks using the RECIST version 1.1 criteria.
The combination of synergistic dual checkpoints inhibition along with ablative radiation may significantly potentiate the local and systemic disease control. This study constitutes the first clinical trial combining effects of SBRT with dual checkpoint blockade with durvalumab and tremelimumab in the treatment of metastatic HNSCC. If positive, this study would lead to a phase III trial testing this treatment combination against standard of care in metastatic HNSCC.
NCT03283605 . Registration date: September 14, 2017; version 1.
The purpose of this study was to determine the prognostic value and oncogenic pathways associated to miRNA expression in squamous cell carcinoma of the oral tongue and to link these miRNA candidates ...with potential gene targets. We performed a miRNA screening within our institutional cohort (n = 58 patients) and reported five prognostic targets including a cluster of four co‐expressed miRNAs (miR‐18a, miR‐92a, miR‐103, and miR‐205). Multivariate analysis showed that expression of miR‐548b (p = 0.007) and miR‐18a (p = 0.004, representative of co‐expressed miRNAs) are independent prognostic markers for squamous cell carcinoma of the oral tongue. These findings were validated in The Cancer Genome Atlas (TCGA) cohort (n = 131) for both miRNAs (miR‐548b: p = 0.027; miR‐18a: p = 0.001). Bioinformatics analysis identified PTEN and ACTN4 as direct targets of the four co‐expressed miRNAs and miR‐548b, respectively. Correlations between the five identified miRNAs and their respective targeted genes were validated in the two merged cohorts and were concordantly significant (miR‐18a/PTEN: p < 0.0001; miR‐92a/PTEN: p = 0.0008; miR‐103/PTEN: p = 0.008; miR‐203/PTEN: p = 0.019; miR‐548b/ACTN4: p = 0.009).
What's new?
MicroRNAs (miRNAs) are increasingly recognized as key regulatory factors in cancer. This study examined their significance specifically in the context of squamous cell carcinoma of the oral tongue (SCCOT). Co‐expression of four miRNAs was found to be inversely correlated with expression of the tumor suppressor PTEN, a downregulator of PI3K/Akt signaling, which is frequently altered in cancer. Increased expression of an additional miRNA, miR‐548b, was inversely correlated with ACTN4, an Akt regulator. The miRNAs were further associated with SCCOT patient prognosis. The findings highlight potential prognostic and therapeutic avenues centering on miRNAs in oral tongue carcinoma.
The aim of this study is to identify clinical factors that are predictive of depression and quality of life (QOL) among long-term survivors of head and neck squamous cell carcinoma and to develop ...predictive scores using these factors.
Cohort study
Tertiary referral center.
A total of 209 posttreatment (median follow-up, 38.7 months) head and neck cancer patients were prospectively evaluated using the Hospital Anxiety Depression Scale (HADS), the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30, and the EORTC Quality of Life Questionnaire Head and Neck 35, and pretreatment patient-related, tumor-related, and treatment-related predictors were identified using chart review. Bivariate (χ(2) and t test) and multivariate (linear regression) analyses were used to construct predictive models.
Significant pretreatment predictors of depression were identified on multivariate analysis as smoking at diagnosis, >14 alcoholic drinks per week, T3 or T4 status, and >3 medications (P < .001). Two or more of these factors yielded an 82.3% sensitivity in detecting significant depressive symptoms (defined as a HADS cutoff score of 5). Significant predictors of fatigue, global health/QOL, social contact, speech, pain, swallowing, and xerostomia were also identified.
Pretreatment predictors of long-term depression and QOL have been defined using multivariate models, and an easily applicable predictive score of long-term depression is proposed. Potential eventual clinical applications include prophylactic intervention in at-risk patients.
•HNSCC patients with rs6942067 GG genotype have a worse overall survival.•HNSCC patients with rs6942067 GG genotype have higher occurrence of N+ tumors.•Occurrency of rs6940267 GG is higher for ...N+ patients young or without risk factors.•Patients with rs6942067 have higher risk of HNSCC than the general population.
The purpose of this study was to determine the prognostic value and oncogenic pathways associated to miRNA expression in squamous cell carcinoma of the oral tongue and to link these miRNA candidates ...with potential gene targets. We performed a miRNA screening within our institutional cohort (
n
= 58 patients) and reported five prognostic targets including a cluster of four co‐expressed miRNAs (miR‐18a, miR‐92a, miR‐103, and miR‐205). Multivariate analysis showed that expression of miR‐548b (
p
= 0.007) and miR‐18a (
p
= 0.004, representative of co‐expressed miRNAs) are independent prognostic markers for squamous cell carcinoma of the oral tongue. These findings were validated in The Cancer Genome Atlas (TCGA) cohort (
n
= 131) for both miRNAs (miR‐548b:
p
= 0.027; miR‐18a:
p
= 0.001). Bioinformatics analysis identified PTEN and ACTN4 as direct targets of the four co‐expressed miRNAs and miR‐548b, respectively. Correlations between the five identified miRNAs and their respective targeted genes were validated in the two merged cohorts and were concordantly significant (miR‐18a/PTEN:
p
< 0.0001; miR‐92a/PTEN:
p
= 0.0008; miR‐103/PTEN:
p
= 0.008; miR‐203/PTEN:
p
= 0.019; miR‐548b/ACTN4:
p
= 0.009).
What's new?
MicroRNAs (miRNAs) are increasingly recognized as key regulatory factors in cancer. This study examined their significance specifically in the context of squamous cell carcinoma of the oral tongue (SCCOT). Co‐expression of four miRNAs was found to be inversely correlated with expression of the tumor suppressor PTEN, a downregulator of PI3K/Akt signaling, which is frequently altered in cancer. Increased expression of an additional miRNA, miR‐548b, was inversely correlated with ACTN4, an Akt regulator. The miRNAs were further associated with SCCOT patient prognosis. The findings highlight potential prognostic and therapeutic avenues centering on miRNAs in oral tongue carcinoma.
A novel tri-modal microscope combining optical coherence tomography (OCT), spectrally encoded confocal microscopy (SECM) and fluorescence imaging is presented. This system aims at providing a tool ...for rapid identification of head and neck tissues during thyroid surgery. The development of a dual-wavelength polygon-based swept laser allows for synchronized, co-registered and simultaneous imaging with all three modalities. Further ameliorations towards miniaturization include a custom lens for optimal compromise between orthogonal imaging geometries as well as a double-clad fiber coupler for increased throughput. Image quality and co-registration is demonstrated on freshly excised swine head and neck tissue samples to illustrate the complementarity of the techniques for identifying signature cellular and structural features.
Obesity has been linked to numerous diseases including thyroid cancer, but the exact nature of the relationship, especially with respect to patients with thyroid nodules, remains unclear. The ...objective of this study was to evaluate the impact of body mass index (BMI) on thyroid cancer risk in a population of patients with indeterminate cytology on fine-needle aspiration biopsy (FNAB).
A total of 253 consecutive patients with indeterminate thyroid nodule FNABs who underwent total thyroidectomy in a tertiary care teaching hospital between 2002 and 2007 were reviewed. Height and weight reported on the anesthesia summary were recorded for each patient. Malignancy rates were calculated for the underweight, normal, overweight, and obese groups stratified according to their BMI. Subanalyses according to age and sex were also performed.
The risk of malignancy tended to be lower in obese patients compared to patients with BMIs in the underweight, normal, and overweight ranges (52% vs. 61%, p = 0.195). In men, a BMI classified as obese was associated with a significantly lower rate of malignancy (36% vs. 72%, p = 0.003). Women older than 45 years were a subgroup in which higher malignancy rates were associated with obesity (65% vs. 54%, p = 0.293). Conversely, in men over the age of 45 years and women under 45 years, a BMI in the obesity range was linked to a lower incidence of malignancy (20% vs. 68% p = 0.009 and 36% vs. 68% p = 0.043, respectively). When older women were excluded from the population studied, the rate of malignancy in obese patients was 36% versus 70% in nonobese patients (p = 0.002) with an associated reduction of 5% in the risk of malignancy per increased unit of BMI.
For patients with FNAB results of indeterminate significance, a higher BMI correlates with lower rates of thyroid malignancy for all patients except women over the age of 45 years.
Protein products of tumor suppressor genes are often involved in regulating the cell cycle, and aberrant expression can correlate with underlying genetic mutations. Mutations in the p16 gene have ...been detected at relatively high rates in squamous cell carcinomas of the oral cavity. However, immunohistochemical staining for the protein product has not been examined as a diagnostic tool for identifying dysplastic lesions in the oral cavity. Sixty cases of biopsies of reactive, inflammatory, and dysplastic lesions of all grades were stained with an antibody to p16INK4A and analyzed for which layer of the epithelium had positive cells. Staining was seen only in the basal or lower third in keratoses and mild dysplasias and was seen in the mid and upper thirds in moderate to severe dysplasia. The staining across larger fragments of biopsied epithelium highlighted skip lesions, with strong staining restricted to dysplastic regions. Inflammatory lesions, including chronic ulcers, showed absent or minimal basal layer staining with p16INK4A. In this preliminary study, p16INK4A shows promise as to a potential marker to aid in recognizing the presence of dysplasia in squamous mucosa of the head and neck, particularly in subtle lesions, and in an inflammatory or ulcerated background.
To determine the value of fine-needle aspiration biopsies (FNABs) of the thyroid and stratify the risk of malignancy within the indeterminate FNAB diagnostic category at our institution.
Case series ...with chart review of preoperative FNABs of consecutive patients who underwent total thyroidectomy between 2005 and 2007.
A total of 115 cases were reviewed, and FNABs were categorized into four groups: benign, positive or suspicious for malignancy, indeterminate (follicular or Hurthle cell lesions), and nondiagnostic. Cytohistologic correlation was then established.
The accuracy of FNAB in detecting thyroid malignancy was 88 percent with false-negative and false-positive rates of 13 percent and 7 percent, respectively. Overall, 52 percent of the indeterminate cases were carcinomas (48 percent of follicular lesions and 62 percent of Hurthle cell lesions). In the presence of cytologic atypia, the rate of malignancy increased to 75 percent and 83 percent for the follicular and Hurthle cell lesions, respectively.
FNAB is an accurate and helpful method for the evaluation of thyroid nodules with results directly correlating with management. Surgery should be considered for FNABs categorized as indeterminate, especially in the presence of cytologic atypia. Because of the high false-negative rate, benign FNABs require close follow-up with ultrasound examination and periodic biopsies.
We aim to present papillary microcarcinoma (PMC) incidence at a university teaching hospital, to compare characteristics of PMC in relation to size, and to assess for significant difference in PMC ...incidence among patients with non-PMC thyroid malignancies.
Pathology results were reviewed for consecutive total thyroidectomies between 2002 and 2007 (n = 860). Statistical significance was calculated using chi(2) or, when unavailable, Fisher exact test.
PMC was found in 429 cases, which is 49.9 percent of all total thyroidectomies. In PMC > or =5 mm, 25.1 percent had extrathyroidal extension vs 9.1 percent for <5 mm (P < 0.001). When 4 mm is used as a threshold, P value was 300-fold smaller. Incidence in patients with any non-PMC thyroid malignancy was 51.6 percent against 47.2 percent in all other patients (P = 0.203).
In this study, PMC was found in 49.9 percent of patients, which, to our knowledge, is higher than any other reported incidence. A threshold of > or =4 mm was more significant than 5 mm for carrying increased risk for extrathyroidal spread. There was no significant difference in PMC incidence in patients with malignant vs benign disease.
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