To devise, validate, and externally test PET/CT radiomics signatures for human papillomavirus (HPV) association in primary tumors and metastatic cervical lymph nodes of oropharyngeal squamous cell carcinoma (OPSCC). We analyzed 435 primary tumors (326 for training, 109 for validation) and 741 metastatic cervical lymph nodes (518 for training, 223 for validation) using FDG-PET and non-contrast CT from a multi-institutional and multi-national cohort. Utilizing 1037 radiomics features per imaging modality and per lesion, we trained, optimized, and independently validated machine-learning classifiers for prediction of HPV association in primary tumors, lymph nodes, and combined “virtual” volumes of interest (VOI). PET-based models were additionally validated in an external cohort. Single-modality PET and CT final models yielded similar classification performance without significant difference in independent validation; however, models combining PET and CT features outperformed single-modality PET- or CT-based models, with receiver operating characteristic area under the curve (AUC) of 0.78, and 0.77 for prediction of HPV association using primary tumor lesion features, in cross-validation and independent validation, respectively. In the external PET-only validation dataset, final models achieved an AUC of 0.83 for a virtual VOI combining primary tumor and lymph nodes, and an AUC of 0.73 for a virtual VOI combining all lymph nodes. We found that PET-based radiomics signatures yielded similar classification performance to CT-based models, with potential added value from combining PET- and CT-based radiomics for prediction of HPV status. While our results are promising, radiomics signatures may not yet substitute tissue sampling for clinical decision-making.

PET/CT radiomics signature of human papilloma virus association in oropharyngeal squamous cell carcinoma

This study aims to identify prognostic factors in nasopharyngeal carcinoma (NPC) to improve the current 8th edition TNM classification. A systematic review of the literature reported between 2013 and 2019 in PubMed, Embase, and Scopus was conducted. Studies were included if (1) original clinical studies, (2) ≥50 NPC patients, and (3) analyses on the association between prognostic factors and overall survival. The data elements of eligible studies were abstracted and analyzed. A level of evidence was synthesized for each suggested change to the TNM staging and prognostic factors. Of 5,595 studies screened, 108 studies (44 studies on anatomical criteria and 64 on non-anatomical factors) were selected. Proposed changes/factors with strong evidence included the upstaging paranasal sinus to T4, defining parotid lymph node as N3, upstaging N-category based on presence of lymph node necrosis, as well as the incorporation of non-TNM factors including EBV-DNA level, primary gross tumor volume (GTV), nodal GTV, neutrophil-lymphocyte ratio, lactate dehydrogenase, C-reactive protein/albumin ratio, platelet count, SUVmax of the primary tumor, and total lesion glycolysis. This systematic review provides a useful summary of suggestions and prognostic factors that potentially improve the current staging system. Further validation studies are warranted to confirm their significance.

/pdf/prognostic-factors-for-overall-survival-in-nasopharyngeal-4qf175q736.pdf

Prognostic Factors for Overall Survival in Nasopharyngeal Cancer and Implication for TNM Staging by UICC: A Systematic Review of the Literature.

Metabolic tumor volume and conformal radiotherapy based on prognostic PET/CT for treatment of nasopharyngeal carcinoma.

A Review of Modern Radiation Therapy Dose Escalation in Locally Advanced Head and Neck Cancer.

Many of the principles established in adults with undifferentiated nasopharyngeal carcinoma (NPC) apply to children, adolescents and young adults. However, NPC in young patients should be distinguished from the adult form by several points. This review focuses mainly on differences between adult and pediatric NPC. The role of biology and genetics in pediatric NPC is discussed. Systemic treatment modalities including type of chemotherapy induction, timing of treatment, role of immunotherapy as adjuvant treatment, or in relapsing/ metastatic diseases are reported. Radiation modalities (doses, techniques…) in children are also reviewed. Long-term effects including secondary cancers are finally be discussed in this young NPC population.

https://www.birpublications.org/doi/pdf/10.1259/bjr.20190107

Update in pediatric nasopharyngeal undifferentiated carcinoma.

Purpose:This retrospective study investigated the effects of cognitive behavioral therapy (CBT) on depression, anxiety, response rates, and adverse events in patients with locoregional advanced nas...

https://journals.sagepub.com/doi/pdf/10.1177/15347354211006179

Effects of Cognitive Behavioral Therapy for Depression and Anxiety, Response Rates and Adverse Events in Patients with Locoregional Advanced Nasopharyngeal Carcinoma.

Reportedly, activation of the NF-B signaling pathway is related to the proliferation of nasopharyngeal carcinoma (NPC) cells; however, the underlying mechanism by which NF-B is activated in NPC cells is yet to be addressed. In our present studies, CREB-binding protein (CBP)-mediated acetylation of the NF-B p65 subunit and its effect on activation of NF-B p65 as well as its role in the proliferation of NPC cells were explored.Human NPC cell lines CNE1 and C666-1 were cultured in vitro. The acetylation (Lys310) and phosphorylation (Ser536) levels of NF-B p65 in NPC cell lines were detected by Western blot. Then, the mRNA levels of CBP, p300, PCAF and GCN5 in NPC cell lines were determined by real-time PCR. Subsequently, the interaction of p65 with CBP in NPC cell lines was detected by a co-immunoprecipitation experiment. Furthermore, an NF-B p65 mutant (at Lys310), NF-B inhibitor and CBP shRNA were used to study the effect of CBP-mediated acetylation of NF-B p65 on the proliferation of NPC cell lines by CCK-8 assay.NF-B p65 was markedly acetylated at the site of Lys310 in NPC cells. Moreover, the mutation of NF-B p65 at the acetylation site markedly reduced proliferation of human NPC cells. Further investigation revealed that CBP was up-regulated and physically associated with NF-B p65 at the protein level in NPC cells. CBP-mediated NF-B p65 acetylation enhanced its phosphorylation and further contributed to the proliferation of NPC cells.This study indicated that CBP-mediated NF-B p65 acetylation promotes the proliferation of NPC cells.

https://www.archivesofmedicalscience.com/pdf-69744-59653?filename=CBP_mediated acetylation.pdf

CBP-mediated acetylation of NF-κB p65 contributes to the proliferation of human nasopharyngeal carcinoma cells

The effect of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT)-guided dose-painting intensity-modulated radiation therapy (IMRT) in locoregionally advanced nasopharyngeal carcinoma (NPC) is unclear. This study aimed to assess the efficacy and toxicity of such combination. From 2012 to 2014, 213 patients with stage III-IVB NPC received chemoradiotherapy by PET/CT-guided DP-IMRT (group A, n = 101) or CT-based IMRT (group B, n = 112). In group A, subvolume GTVnx-PET (gross tumor volume of nasopharynx in PET images) was defined within GTVnx (gross tumor volume of nasopharynx) as the SUV50%max isocontour; the dose to GTVnx-PET was escalated to DT 75.2 Gy/32 and 77.55 Gy/33 Fx, respectively, for patients with T1-2 and T3-4 disease, respectively. In group B, PGTVnx was irradiated at DT 70.4–72.6 Gy/32–33 Fx in 2.2 Gy per fraction. Complete response rates were 99.0% (100/101) and 92.9% (104/112) in groups A and B, respectively (P = 0.037). Compared with CT-based IMRT, FDG-PET/CT guided DP-IMRT significantly improved 3-year local failure-free survival (LFFS, 98.8% vs. 91.3%; P = 0.032), locoregional failure-free survival (LRFFS, 97.2 vs. 91.2%; P = 0.049), distant metastasis-free survival (DMFS, 92.9% vs. 87.4%; P = 0.041), disease free survival (DFS, 87.9% vs. 82.4%; P = 0.02), and overall survival (OS, 91.8% vs. 82.6%; P = 0.049). No statistically significant differences in acute and late toxic effects were observed. Multivariate analysis showed that dose painting (PET/CT-guided DP-IMRT vs CT-based IMRT without DP) was a significant independent prognostic factor for LFFS and DFS. FDG-PET/CT guided DP-IMRT plus chemotherapy is associated with a considerable survival benefit, without increasing toxicity in patients with locoregional advanced NPC. Further randomized trials are needed to fully assess the role of PET/CT-guided DP-IMRT.

/pdf/pet-ct-guided-dose-painting-versus-ct-based-intensity-1gp36pi5py.pdf

PET/CT-guided dose-painting versus CT-based intensity modulated radiation therapy in locoregional advanced nasopharyngeal carcinoma

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Papers

Effects of Cognitive Behavioral Therapy for Depression and Anxiety, Response Rates and Adverse Events in Patients with Locoregional Advanced Nasopharyngeal Carcinoma.

CBP-mediated acetylation of NF-κB p65 contributes to the proliferation of human nasopharyngeal carcinoma cells

PET/CT-guided dose-painting versus CT-based intensity modulated radiation therapy in locoregional advanced nasopharyngeal carcinoma