scholarly journals E1 Detection as Prognosticator in Human Papillomavirus-Positive Head and Neck Cancers

2016 ◽  
Vol 31 (2) ◽  
pp. 163-172
Author(s):  
Daniela Vivenza ◽  
Cristiana Lo Nigro ◽  
Nerina Denaro ◽  
Mirella Fortunato ◽  
Martino Monteverde ◽  
...  

Purpose HPV-related locally advanced head and neck cancers (LA-HNCs) show a good prognosis. This study aimed to investigate the HPV prevalence in LA-HNCs and compare the prognostic value of E1, E6 and L1 genomic viral fragments and p16, individually and in combination, in order to find the best prognosticator in terms of overall survival (OS) and progression-free survival (PFS). Patients and Methods HPV16 was searched in 255 LA-HNC formalin-fixed paraffin-embedded tumor tissues, 89 oropharyngeal cancers (OPCs), and 166 non-OPCs by DNA-PCR with 3 primer pairs. p16 was analyzed by immunohistochemistry in 235 patients. Results The prevalence of positive samples decreased constantly from E6 to L1 and E1 in both OPCs and non-OPCs. Each LA-HNC patient highlighted variable positivity for each fragment. OPCs showed a higher prevalence of positive samples compared to non-OPCs. Positive coexistence of all the fragments was more common in OPCs (31.5%) than non-OPCs (4.2%), and E1 detection was always associated with E6 and L1. E1-positive OPCs showed improved OS (p = 0.012) and PFS (p = 0.036), while L1- or E6-positive ones did not. p16-positive patients were more prevalent in the OPC (29.8%) than the non-OPC group (7.3%) (p<0.0001) and its prognostic value was not superior to that of E1. However, the multivariate Cox analysis which included E1, L1, E6 status and p16 expression did not show a significant p value. Conclusions Though HPV16 positivity measured by DNA-PCR was higher for L1 and E6, they performed weakly as prognosticators; E1 might become a strong prognostic marker for OS and PFS in OPCs.

Medicina ◽  
2020 ◽  
Vol 57 (1) ◽  
pp. 6
Author(s):  
Camil Ciprian Mireştean ◽  
Anda Crişan ◽  
Călin Buzea ◽  
Roxana Irina Iancu ◽  
DragoşPetru Teodor Iancu

The combination of immune checkpoint inhibitors and definitive radiotherapy is investigated for the multimodal treatment of cisplatin non-eligible locally advanced head and neck cancers (HNC). In the case of recurrent and metastatic HNC, immunotherapy has shown benefit over the EXTREME protocol, being already considered the standard treatment. One of the biggest challenges of multimodal treatment is to establish the optimal therapy sequence so that the synergistic effect is maximal. Thus, superior results were obtained for the administration of anti-CTLA4 immunotherapy followed by hypofractionated radiotherapy, but the anti-PD-L1 therapy demonstrates the maximum potential of radio-sensitization of the tumor in case of concurrent administration. The synergistic effect of radiotherapy–immunotherapy (RT–IT) has been demonstrated in clinical practice, with an overall response rate of about 18% for HNC. Given the demonstrated potential of radiotherapy to activate the immune system through already known mechanisms, it is necessary to identify biomarkers that direct the “nonresponders” of immunotherapy towards a synergistic RT–IT stimulation strategy. Stimulation of the immune system by irradiation can convert “nonresponder” to “responder”. With the development of modern techniques, re-irradiation is becoming an increasingly common option for patients who have previously been treated with higher doses of radiation. In this context, radiotherapy in combination with immunotherapy, both in the advanced local stage and in recurrent/metastatic of HNC radiotherapy, could evolve from the “first level” of knowledge (i.e., ballistic precision, dose conformity and homogeneity) to “level two” of “biological dose painting” (in which the concept of tumor heterogeneity and radio-resistance supports the need for doses escalation based on biological criteria), and finally to the “third level“ ofthe new concept of “immunological dose painting”. The peculiarity of this concept is that the radiotherapy target volumes and tumoricidal dose can be completely reevaluated, taking into account the immune-modulatory effect of irradiation. In this case, the tumor target volume can include even the tumor microenvironment or a partial volume of the primary tumor or metastasis, not all the gross and microscopic disease. Tumoricidal biologically equivalent dose (BED) may be completely different from the currently estimated values, radiotherapy treating the tumor in this case indirectly by boosting the immune response. Thus, the clinical target volume (CTV) can be replaced with a new immunological-clinical target volume (ICTV) for patients who benefit from the RT–IT association (Image 1).


2000 ◽  
Vol 18 (7) ◽  
pp. 1458-1464 ◽  
Author(s):  
Branislav Jeremic ◽  
Yuta Shibamoto ◽  
Biljana Milicic ◽  
Nebojsa Nikolic ◽  
Aleksandar Dagovic ◽  
...  

PURPOSE: To investigate whether the addition of cisplatin (CDDP) to hyperfractionation (Hfx) radiation therapy (RT) offers an advantage over the same Hfx RT given alone in locally advanced (stages III and IV) squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: One hundred thirty patients were randomized to receive either Hfx RT alone to a tumor dose of 77 Gy in 70 fractions in 35 treatment days over 7 weeks (group I, n = 65) or the same Hfx RT and concurrent low-dose (6 mg/m2) daily CDDP (group II, n = 65). RESULTS: Hfx RT/chemotherapy offered significantly higher survival rates than Hfx RT alone (68% v 49% at 2 years and 46% v 25% at 5 years; P = .0075). It also offered higher progression-free survival (46% v 25% at 5 years; P = .0068), higher locoregional progression-free survival (LRPFS) (50% v 36% at 5 years; P = .041), and higher distant metastasis-free survival (DMFS) (86% v 57% at 5 years; P = .0013). However, there was no difference between the two treatment groups in the incidence of either acute or late high-grade RT-induced toxicity. Hematologic high-grade toxicity was more frequent in group II patients. CONCLUSION: As compared with Hfx RT alone, Hfx RT and concurrent low-dose daily CDDP offered a survival advantage, as well as improved LRPFS and DMFS.


2010 ◽  
Vol 2 (1) ◽  
pp. 43-51
Author(s):  
Vedang Murthy ◽  
Sayan Kundu ◽  
Tanweer Shahid ◽  
Ashwini Budrukkar ◽  
Tejpal Gupta ◽  
...  

Abstract Though early stage head and neck cancers can be cured either by surgery or radiation, patients with locally advanced disease continues to pose a therapeutic challenge. Locoregional failure is the major cause of death in head and neck cancers. As the outcome of locally advanced head and neck cancer is less than promising, a combined modality approach is generally undertaken in this group of patients. The combination of surgery, radiation and more recently, chemotherapy and targeted therapy can improve outcomes in locally advanced head and neck cancer patients. This overview discusses the rationale and role of postoperative radiotherapy (PORT) in advanced head and neck cancers, the radiotherapy technique in brief and methods of enhancing the efficacy of postoperative RT by altering the fractionation schedules and adding chemotherapy and targeted therapy.


2021 ◽  
Vol 108 (Supplement_6) ◽  
Author(s):  
A Rajgor ◽  
A McQueen ◽  
T Ali ◽  
E Aboagye ◽  
B Obara ◽  
...  

Abstract Background Radiomics is a novel method of extracting data from medical images that is difficult to visualise through the naked eye. This technique transforms digital images that hold information on pathology into high-dimensional-data for analysis. Radiomics has the potential to enhance laryngeal cancer care and to date, has shown promise in various other specialties. Aim The aim of this review is to summarise the applications of this technique to laryngeal cancer and potential future benefits. Method A comprehensive systematic review-informed search of the MEDLINE and EMBASE online databases was undertaken. Keywords ‘laryngeal cancer’ OR ‘larynx’ OR ‘larynx cancer’ OR ‘head and neck cancer’ were combined with ‘radiomic’ OR ‘signature’ OR ‘machine learning’ OR ‘artificial intelligence’. Additional articles were obtained from bibliographies using the ‘snowball method’. Results Seventeen articles were identified that evaluated the role of radiomics in laryngeal cancer. Two studies affirmed the value of radiomics in improving the accuracy of staging, whilst fifteen studies highlighted the potential prognostic value of radiomics in laryngeal cancer. Twelve (of thirteen) studies incorporated an array of different head and neck cancers in the analysis and only one study assessed laryngeal cancer exclusively. Conclusions Literature to date has various limitations including, small and heterogeneous cohorts incorporating patients with head and neck cancers of distinct anatomical subsites and stages. The lack of uniform data on solely laryngeal cancer and radiomics means drawing conclusions is difficult, although these studies have affirmed its value. Further large prospective studies exclusively in laryngeal cancer are required to unlock its true potential.


2017 ◽  
Vol 72 ◽  
pp. S106 ◽  
Author(s):  
M. Sultania ◽  
S.V.S. Deo ◽  
N.K. Shukla ◽  
A. Sharma ◽  
R.K. Sahu ◽  
...  

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Dr/Khaled Abdel Karim ◽  
Dr/Khaled Nagib ◽  
Dr/Ahmed Hassan Abd El Aziz ◽  
Christina Gamil Garas

Abstract Background Lung cancer is the leading cause of cancer death worldwide, but little is known about how patients with this disease are managed. Aim of the Work We aim to study patterns of care and treatment pathways of non- surgically managed early and locally advanced NSCLC patients from January 2015 to December 2018 in Ain Shams University Clinical Oncology Department. Patients and Methods In this retrospective analysis we included patients the met the following criteria; age &gt;18, histologically confirmed NSCLC patients whom didn’t undergo surgical resection with at least 6 months of follow up data. We collected data from Clinical Oncology department archive in Ain Shams university hospital. Our primary objective is to identify the patterns of care and treatment pathway for non surgically managed NSCLC patients in ASUCOD from January 2015 to December 2018. Results 86 patients finally met our inclusion criteria. Median age at diagnosis of 61 years with a range of (38-85), 95.3% were male. Most of the patients were stage III; 40.7% were stage IIIA, 41.9% were stage IIIB, and 9.3% were stage IIIC. 41 were treated radically, 37 received palliative treatment and only 8 patients received supportive care. Overall median progression free survival in our patients was 9.23 (7.4-13.5) and overall survival duration was13.4 (9.5-18.0). In radically treated patients, 68.3% received sequential chemoradiotherapy (sCRT), 29.2% received concurrent chemoradiotherapy (cCRT) or 2.4% received definitive radiotherapy alone (RT). In palliative treated patients, 73% received chemotherapy alone (CTX), 8.1% received palliative RT and 18.9% received both chemotherapy and palliative dose of radiotherapy (CRT). All treatment modalities were similar regarding median progression free survival and overall survival durations, 17.5 (3.6–19.6) and 20.6 (3.6–31.6) in cCRT, 17.5 (3.6–19.6) and 23.3 (17.7–31.2) in sCRT, 12.9 and 13.4 RT group, P value=0.57 and 0.16 receptively. Similarly, progression free survival and overall survival durations were 8.8 (3.0–15.8) and 16.2 (3.6–18.7) in CRT, 5.3 (0.4–7.6) and 8.6 (6.2–10.2) in CTX, 8.5 (0.4–8.5) and 8.5 (0.4–8.5) in palliative RT group, P value=0.64 and 0.15 receptively. In our study, first-line chemotherapy were Gemcitabine plus Cisplatin (41.9%) or Carboplatin (35.1%).The Second -line chemotherapy were Docetaxel (63.1%) or Paclitaxel plus Carboplatin (26.3%). Paclitaxel plus Carboplatin were the most regimen given with RT. Most of the patients received radiation dose of 60Gy/30Fr (73.2%). Regarding the incidence of toxicity, there were significant high rates of esophagitis in cCRT in grade 3 or more compared to sCRT. Conclusion We have found that less than half of this study population were treated radically while the other half received palliative treatment. And only few patients received best supportive care. Radically treated patients had higher progression free survival and overall survival durations compared to palliative and supportive treatment.


2018 ◽  
pp. 1-11 ◽  
Author(s):  
Safi Shahda ◽  
Kirsten M. Timms ◽  
Ashley A. Ibrahim ◽  
Julia E. Reid ◽  
Harvey M. Cramer ◽  
...  

Purpose Mutations or copy number abnormalities of genes involved in homologous recombination (HR) occur in pancreatic ductal adenocarcinoma (PDAC). DNA-based measures of HR deficiency (HRD) have been developed and may help identify tumors with better response to DNA-damaging agents. This study aimed to describe the HR pathway mutations and HRD status and determine their association with treatment response and outcome in patients with PDAC. Patients and Methods We performed a retrospective analysis of tumor samples from patients treated at Indiana University for locally advanced or metastatic PDAC. Patients were included if they received gemcitabine plus nanoparticle albumin-bound paclitaxel (control) or fluorouracil, oxaliplatin, leucovorin, and irinotecan (FOLFIRINOX) and had adequate follow-up to assess survival and response to therapy. Tumor analysis generated a three-biomarker HRD score and mutation data for 44 genes. Results Ninety-one samples met inclusion criteria, and 78 samples (formalin-fixed paraffin-embedded, n = 15; fine-needle aspiration, n = 63) generated mutation data. HRD analysis was successful for 57 samples (HRD score: median, 18; range, 5 to 61); the primary cause of failure was low tumor cellularity. Six BRCA1/ 2 mutations were detected, four with HRD scores in the top decile ( P = .011). There was no statistically significant correlation between HRD score and radiographic response (odds ratio per interquartile range, 1.40; P = .32 adjusted for treatment) in either treatment group. In patients treated with FOLFIRINOX, HRD score dichotomized at the median was not associated with progression-free survival (median, 5.3 v 9.4 months for low v high HRD score, respectively; P = .083) or overall survival (median, 11.9 v 10.7 months for low v high HRD score, respectively; P = .76). Conclusion Mutations in DNA repair genes occur in PDAC, and HRD scores can be generated in the majority of patients. The HRD score was not significantly associated with higher response rate or prolonged survival in patients treated with FOLFIRINOX.


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