Lawrence J. Oh, Rebecca Asher, Michael Veness, Robert Smee, David Goldstein, N. Gopalakrishna Iyer, Deepak Balasubramanian, Tsu-Hui (Hubert) Low, Carsten E. Palme, Ruta Gupta, Jonathan Clark
Publication date 23-02-2021
In developing countries, oral squamous cell carcinoma (OSCC) is predominantly a cancer affecting older males who smoke tobacco. In countries with effective public health strategies, smoking rates are declining rapidly. It is not clear if patients who develop OSCC without these traditional risk factors represent a clinically distinct cohort with different prognosis. A recent analysis found that elderly non-smoking females with OSCC had significantly worse prognosis, concluding that this was a distinct patient population with poorer survival. The primary aim of this study was to determine the effect of gender and age on prognosis in OSCC, and the interaction between these two variables. Multinational multi-institutional data were collected from six sites. The primary outcome of interest was disease specific survival (DSS). Time to local, regional, and distant recurrence were investigated as secondary outcomes. 3379 patients with OSCC were included. Males had significantly worse DSS compared to females (HR 1.24, 95% CI 1.08-1.43, p = 0.003). Females <70 years of age had significantly better DSS compared to females ≥70 years of age (HR 0.69, 95% CI 0.51-0.94, p < 0.001) but elderly females had similar DSS to males, regardless of age. When age was divided into three groups, the middle-aged group (45-69 years) had a significantly better DSS compared to elderly patients (HR 0.87, 95%CI 0.78-0.96, p < 0.001), however younger patients had similar DSS to elderly patients. When the effect of age (young v middle v elderly) was compared in each gender, young and middle-aged females had the most favourable DSS (log-rank p < 0.001). Middle-aged females who smoked had a 10% survival advantage compared to middle-aged males that smoked at five years. Age, gender, tumour subsite, and smoking status are important drivers of survival in OSCC. However, gender appears to be the most important predictor with young and middle-aged females having the most favourable prognosis.
Pubmed PDF WebSilvia Helena Barem Rabenhorst, Rafael Lima Verde Osterne, Cassiano Francisco Weege Nonaka, Andre Montezuma Sales Rodrigues, Renato Luiz Maia Nogueira, Rommel Mário Rodriguez Burbano, Roberta Barroso Cavalcante
Publication date 21-02-2021
To identify chromosome deletions in 1q25, 1p36 and 1pTEL, and chromosome 17 ploidy status in oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC). Samples from 57 OED and 63 OSCC were selected. FISH was performed using centromeric probes 17 and n LSIR 1p36/LSI 1q25 Dual Color Probe. In OED, deletions were found only in 1pTEL region (29.8%). In OSCC, there was a higher frequency of deletion in 1pTEL (79.4%), followed by 1p36 (73.0%), and 1q25 (20.6%). Advanced TNM clinical stages (III/IV) showed all the deletions studied; at early clinical stages (I/II) of OSCC, deletions were observed only in 1pTEL. The frequency of deletion in 1p36 was 17.0 times higher in OSCC at advanced clinical stages (PR: 17.00). The median number of cell nuclei with chromosome 17 aneuploidy was higher in OSCC than in OED (P < 0.001). Early clinical stages of OSCC showed lower median number nuclei with aneuploidy when compared to advanced tumors (P < 0.05). Tumors harboring deletions in 1p36, 1q25 and 1pTEL revealed higher median numbers of trisomic/polysomic nuclei when compared to lesions exhibiting no abnormalities in chromosome 1 (P < 0.05). A higher prevalence of chromosomal abnormalities was found in OSCC than in OED, while in OSCC, higher abnormalities were present in lesions with higher TNM staging. 1pTEL deletion and monosomy of chromosome 17 are possible markers for progression of OED to OSCC. 1p36 deletion and trisomy/polysomy of chromosome 17 could be markers of worse prognosis of OSCC.
Pubmed PDF WebM. Newman, P.T. Dziegielewski, N.T.A. Nguyen, H.S. Seikaly, M. Xie, D.A. OConnell, J.R. Harris, V.L. Biron, M.K. Gupta, S.D. Archibald, B.S. Jackson, J.E.M. Young, K.J. Keyes, D.S. Nichols, H. Zhang
Publication date 23-02-2021
Current research is elucidating how the addition of depth of invasion (DOI) to the 8th edition of the American Joint Committee on Cancer (AJCC) TNM staging for oral cavity squamous cell carcinoma influences its prognostic accuracy. However, there is limited research on survival in pT3N0M0 oral tongue SCC (OTSCC) patients when stratifying by DOI.
Determine 5-year overall survival (OS), and cancer-specific survival (CSS) for patients with pT3N0M0 oral OTSCC based on shallow DOI (<10 mm) and deep DOI (10-20 mm).
Retrospective review involving three tertiary care cancer centers in North America. cT3N0M0 OTSCC patients receiving primary surgical treatment from 2004 to 2018 were identified.
Inclusion: age > 18 years old and confirmation of pT3N0M0 OTSCC on surgical pathology.
Exclusion: patients undergoing palliative treatment or previous head and neck surgery/radiotherapy.
Analysis comprised two groups: shallow pT3 (tumor diameter > 4 cm, DOI < 10 mm) and deep pT3 (DOI 10 mm-20 mm).
One hundred and four patients with pT3N0M0 OTSCC were included. Mean age was 59.1 years (range: 18-80.74). Age, gender, and Charlson Comorbidity Index were similar between the two groups (p > 0.05). Recurrence, LVI, PNI, and positive margins were more common in deep T3 tumors (P < 0.05). 5-year OS (50% vs 26%, p = 0.006) and CSS (72% vs 24%, p = 0.005) were worse in deep pT3 tumors. Deep pT3 disease was an independent predictor of OS (p = 0.004) and CSS (p = 0.01) on Cox-Regression analysis.
DOI is an independent predictor of poor survival in pT3N0M0 OTSCC patients. Consideration should be given to escalating adjuvant therapy for deep pT3N0M0 OTSCC patients.
Lawrence J. Oh, Laveniya Satgunaseelan, Rebecca Asher, Michael Veness, Robert Smee, David Goldstein, N. Gopalakrishna Iyer, Deepak Balasubramanian, Hubert Low, Carsten E. Palme, Ruta Gupta, Jonathan R. Clark
Publication date 07-02-2021
Over the last few decades evidence has accumulated for increasing incidence of oral cavity squamous cell carcinoma (OSCC) in a younger cohort. Prior studies examining the effect of age at diagnosis on prognosis have produced conflicting data. A multi-institutional cohort study was performed across 6 different sites in Australia, Canada, India and Singapore. Disease-free (DFS), overall (OS) and disease-specific (DSS) survival were analysed. The association of the number of adverse features with survival outcomes was investigated. From 3179 patients, age was a significant predictor of OS with patients older than 45 years having a 66% increased risk of death (HR 1.66, 95%CI 1.33 - 2.07, p < 0.001). The number of adverse features was a significant predictor of OS with 3 or more adverse features having a 199% increased risk (HR 2.99, 95%CI 2.61-3.43. p < 0.001). The estimate effect was greater in patients ≤ 45 years (HR 3.49 vs HR 2.81). Age was not a significant predictor of DSS with similar rates of death from OSCC in multivariable models. The number of adverse features was a significant predictor of DFS with ≥ 3 adverse features having a 140% increased risk of death. The number of adverse features was a significant predictor of DSS with ≥ 3 adverse features having a 230% increased risk of disease specific death. Age is not an independent predictor of disease specific mortality in OSCC. Differences in outcomes are due to the confounding effect of adverse clinicopathological features and the ability to tolerate surgery and adjuvant therapy.
Pubmed PDF WebAnn-Kristin Iro, Abbas Agaimy, Sarina Katrin Müller, Matti Sievert, Heinrich Iro, Konstantinos Mantsopoulos
Publication date 23-02-2021
The aim of this study was to thoroughly investigate the incidence of satellite nodules (SN) and some of their characteristics (number, distance to main lesion) in a large series of pleomorphic adenomas (PA) and to compare several surgical modalities regarding their efficacy in addressing this critical morphological feature. The records of all patients treated for primary PA of the parotid gland between 2006 and 2020 were studied retrospectively. All the histological slides of all tumours were critically re-evaluated for this study by an experienced head and neck pathologist. 845 cases made up our initial study sample. SNs were detected in 68/845 cases (8%). No statistically significant difference could be detected in the incidence of SNs in the surgical specimens between the patient groups managed by extracapsular dissection (46/577, 7.9%) and facial nerve dissecting surgery (22/268, 8.2%, p = 0.502). In the group of cases with SNs, no recurrences were detected (mean follow-up time: 71.4 months). The mean distance from the main lesion to the most distant SN was 1.1 mm (0.08-6.3 mm). The mean size of the SN was 1.9 mm (0.1-9.7 mm). Altogether, the mean distance from the main lesion to the outer periphery of the most distant SN was 3.1 mm (0.4-10.5 mm). Our analysis could not award SNs the title of an "extracapsular dissection's nightmare". In the majority of cases, their favourable histological patterns offer the ideal circumstances for their surgical inclusion in a tumour specimen.
Pubmed PDF WebS. Hamad Sagheer, Brian Swendseid, James Evans, Mindy Rabinowitz, Gurston Nyquist, Marc R. Rosen, Elina Toskala, Ryan Heffelfinger, Adam J. Luginbuhl, Joseph M. Curry
Publication date 17-02-2021
Local reconstruction of central skull base defects may be inadequate for large defects or reoperative cases; free tissue transfer may be necessary. Inset of the flap and management of the pedicle can be challenging. We report our experience and approaches. Retrospective review identifying seven patients with central skull base defects who underwent free flap reconstruction from 2016 to 2020. Four patients with recurrent nasopharyngeal carcinoma, one with recurrent craniopharyngioma, one with clival-cervical chordoma, and one with meningioma of the middle cranial fossa were analyzed. Six defects were closed with an anterolateral thigh free flap and one with a radial forearm free flap. In two patients, the flap was secured in an onlay fashion to the defect via a Caldwell-Luc transmaxillary approach. In one patient, the flap was passed transorally, and the pedicle was delivered into the neck via Penrose drain. In two patients, a parapharyngeal technique and in two others, a retropharyngeal was used for nasopharyngeal inset with endoscopic assistance. There were no flap failures, with an average follow-up time of 20.1 (range 3.2-47.1) months. One patient required flap repositioning on postoperative day three due to midline shift and intracranial contents compression. The transoral inset flap necessitated flap repositioning on postoperative day 13 to improve the nasopharyngeal airway. Free flap reconstruction of the central skull base is challenging, but transmaxillary, transoral, parapharyngeal, and retropharyngeal approaches can be used with endoscopic assistance to ensure secure inset flap and avoid airway obstruction.
Pubmed PDF WebKshitij Parag-Sharma, Jason Tasoulas, Adele M. Musicant, Carlos H. Viesi do Nascimento-Filho, Zhichuan Zhu, Chloe Twomey, Pengda Liu, Rogerio M. Castilho, Antonio L. Amelio
Publication date 14-02-2021
Mucoepidermoid carcinoma (MEC) is the most common type of salivary gland malignancy. Advanced or high-grade MECs are refractory to chemotherapy, often leading to tumor recurrence/metastasis and abysmal ~35% 5-year survival. Causal links have been established between Epithelial Growth Factor Receptor (EGFR) activation and poor outcome. Herein we investigated the therapeutic efficacy of EGFR inhibition against MEC using in vitro pre-clinical models. Five human MEC cell lines were used in cell viability, cytotoxicity, apoptosis, cell cycle, 2D-clonogenicity, and 3D-spheroid formation assays following treatment with Erlotinib (EGFR inhibitor), SAHA (Histone Deacetylase inhibitor; HDAC) and CUDC-101 (dual EGFR-HDAC inhibitor). Effects on MEC cancer stem cells were evaluated using flow cytometry. Gene expression and pathway regulation were evaluated via qPCR and Western blot, respectively. MEC cells enter a quiescent, non-proliferative yet rapidly reversible drug tolerant state upon EGFR inhibition. Despite robust suppression of MEC cell proliferation, no discernable apoptosis is detected. Combination of EGFR and HDAC inhibitors exhibits synergistic effects, exerting ~5-fold more potent cell cytotoxicity compared to HDAC or EGFR monotherapy. CUDC-101, a single molecule with dual EGFR-HDAC inhibitor moieties, exerts irreversible and potent cytotoxic activity against MEC cells and blunts MEC cancer stem-cell tumorigenicity. MEC cells are intrinsically tolerant to EGFR inhibition. Combining EGFR and HDAC inhibitors exerts synergistic and potent cytotoxic effects, suggesting that EGFR inhibitors still hold significant promise against MEC. Future studies are needed to assess the applicability and efficacy of dual EGFR-HDAC inhibitors for the clinical management of MEC.
Pubmed PDF WebAngelina M.M. Santoso, Femke Jansen, Birgit I. Lissenberg-Witte, Robert J. Baatenburg de Jong, Johannes A. Langendijk, C. René Leemans, Johannes H. Smit, Robert P. Takes, Chris H.J. Terhaard, Annemieke van Straten, Irma M. Verdonck-de Leeuw
Publication date 14-02-2021
Patients with head and neck cancer (HNC) often report disturbances in their sleep quality, impairing their quality of life. This study aims to examine the trajectories of sleep quality from diagnosis up to 6-month after treatment, as well as the pre-treatment risk factors for poor sleep trajectories. Sleep quality (Pittsburgh sleep quality index) was measured shortly after diagnosis (pre-treatment), and at 3 and 6 months after finishing treatment. Patients were categorized into 5 trajectory groups. We examined the association of sleep quality trajectories with sociodemographic and clinical characteristics, coping style, HNC symptoms, and psychological distress. Among 412 included patients, about a half either had a persistent good sleep (37.6%) or an improving (16.5%) trajectory. About a third had a persistent poor sleep (21.8%) or worsening (10.9%) sleep trajectory. The remaining patients (13.1%), alternated between good and poor sleep. Using persistent good sleep as a reference outcome, persistent poor sleepers were more likely to be woman (odds ratio [OR] = 1.98, 95% confidence interval [CI] 1.01-3.90), use painkillers prior to treatment (OR = 2.52, 95% CI 1.33-4.77), and have more pre-treatment anxiety symptoms (OR = 1.26, 95% CI 1.15-1.38). Unfavorable sleep quality trajectories are prevalent among HNC patients from pre-treatment to 6-month after treatment. A periodic sleep evaluation starting shortly after HNC diagnosis is necessary to identify persistent sleep problems, especially among high-risk group.
Pubmed PDF WebSung Jun Ma, Austin J. Iovoli, Kristopher Attwood, Kimberly E. Wooten, Hassan Arshad, Vishal Gupta, Ryan P. McSpadden, Moni A. Kuriakose, Michael R. Markiewicz, Jon M. Chan, Wesley L. Hicks, Mary E. Platek, Andrew D. Ray, Elizabeth A. Repasky, Mark K. Farrugia, Anurag K. Singh
Publication date 13-02-2021
To assess the association between financial toxicity and survival in patients with head and neck cancer (HNC). Using a single-institution database, we retrospectively reviewed HNC patients treated at Roswell Park Comprehensive Cancer Center treated with definitive or postoperative radiation therapy between 2013 and 2017. Kaplan-Meier method and log-rank tests were used to analyze survival outcomes. Propensity score matching on all clinically relevant baseline characteristics was performed to address selection bias. All statistical tests were two-sided and those less than 0.05 were considered statistically significant. Of a total of 284 HNC patients (age: median 61 years, IQR 55-67; 220 [77.5%] men), 204 patients (71.8%) received definitive radiation and 80 patients (28.2%) received adjuvant radiation. There were 41 patients (14.4%) who reported high baseline financial toxicity. Chemotherapy was used in 237 patients (83.5%). On multivariable analysis, those with high financial toxicity exhibited worse overall survival (hazards ratio [HR] 1.75, 95% confidence interval [CI] 1.05-2.94, p = 0.03) and cancer specific survival (HR 2.28, 95% CI 1.31-3.96, p = 0.003). On matched pair analysis of 66 patients, high financial toxicity remained associated with worse OS (HR 2.72, 95% CI 1.04-7.09, p = 0.04) and CSS (HR 3.75, 95% CI 1.22-11.5, p = 0.02). HNC patient reported baseline financial toxicity was significantly correlated with both decreased overall and cancer specific survival. These significant correlations held after match pairing. Further research is warranted to investigate the impact of financial toxicity in HNC and mitigate its risk.
Pubmed PDF WebHoward Yu-hao Liu, Laura Tam, Neil M. Woody, Jimmy Caudell, Chandana A. Reddy, Ahmed Ghanem, Matthew Schymick, Nikhil Joshi, Jessica Geiger, Eric Lamarre, Brian Burkey, David Adelstein, Neal Dunlap, Farzan Siddiqui, Shlomo Koyfman, Sandro Virgilio Porceddu
Publication date 14-02-2021
The importance of treating the bilateral neck in lateralized small oral cavity squamous cell carcinoma (OCC) is unclear. We sought to define the incidence and predictors of contralateral neck failure (CLF) in patients who underwent unilateral treatment. We performed a multi-institutional retrospective study of patients with pathologic T1-T2 (AJCC 7th edition) OCC with clinically node negative contralateral neck who underwent unilateral treatment with primary surgical resection ± adjuvant radiotherapy between 2005 and 2015. Incidence of CLF was estimated using the cumulative incidence method. Clinicopathological factors were analyzed by univariate (UVA) and multivariate analysis (MVA) for possible association with CLF. Kaplan-Meier analysis was used to estimate overall survival (OS). 176 patients were evaluated with a median of 65.9 months of follow-up. Predominant pathologic T-stage was T1 (68%), 8.5% of patients were N1, 2.8% were N2b. Adjuvant radiotherapy was delivered to 17% of patients. 5-year incidence of CLF was 4.3% (95% CI 1.2-7.4%). Depth of invasion (DOI) > 10 mm and positive ipsilateral neck node were significant predictors for CLF on UVA. DOI > 10 mm remained significant on MVA (HR = 6.7, 95% CI 1.4-32.3, p = 0.02). The 2- and 5-year OS was 90.6% (95% CI 86.2-95.0%) and 80.6% (95% CI 74.5-86.8%), respectively. Observation of the clinically node negative contralateral neck in small lateralized OCC can be a suitable management approach in well selected patients, however caution should be applied when DOI upstages small but deeply invasive tumors to T3 on 8th edition AJCC staging.
Pubmed PDF WebDouglas R. Adkins, Jin-Ching Lin, Assuntina Sacco, Jessica Ley, Peter Oppelt, Vyacheslay Vanchenko, Nataliia Komashko, Chia-Jui. Yen, Trisha Wise-Draper, Jose Lopez-Picazo Gonzalez, Sinisa Radulovic, Qi Shen, Holger Thurm, Jean-François Martini, Justin Hoffman, Xin Huang, Bohuslav Melichar, Makoto Tahara
Publication date 12-02-2021
This study examined whether palbociclib and cetuximab prolonged overall survival (OS) versus placebo and cetuximab. In this double-blind, randomized, phase 2 trial (PALATINUS), patients with platinum-resistant, cetuximab-naïve, human papillomavirus-unrelated recurrent/metastatic head and neck squamous-cell carcinoma received cetuximab and either palbociclib (arm A) or placebo (arm B). The primary endpoint was OS; 120 patients were required to have ≥80% power to detect a hazard ratio (HR) of 0.6 (median OS of 10 months in arm A and 6 months in arm B) using a one-sided, log-rank test (P = 0.10). 125 patients were randomized (arm A: 65, arm B: 60). Median follow-up was 15.9 months (IQR, 11.3-22.7). Median OS was 9.7 months in arm A and 7.8 months in arm B (HR, 0.82; 95% CI, 0.54-1.25; P = 0.18). Median progression-free survival was 3.9 months in arm A and 4.6 months in arm B (HR, 1.00; 95% CI, 0.67-1.5; P = 0.50). The most common treatment-related adverse events in arm A were rash (39 patients, 60.9%) and neutropenia (26, 40.6%; three febrile) and in arm B was rash (32, 53.3%). There was no significant difference in median OS with palbociclib and cetuximab versus placebo and cetuximab. Pfizer Inc (NCT02499120).
Pubmed PDF WebLuo Huang, Xin Zhang, Yu Bai, Kevin L.M. Chua, Yue Xie, Xiaolei Shu, Bin Long, Chunbo Fan, Darren W.T. Lim, Sze Huey Tan, Joseph T.S. Wee, Ying Wang, Yongzhong Wu, Melvin L.K. Chua
Publication date 21-02-2021
There is no standard-of-care for recurrent, metastatic nasopharyngeal carcinoma (rmNPC) after first-line chemotherapy. Here, we report the efficacy and safety data of apatinib in rmNPC patients. Thirty-five biopsy-proven rmNPC patients received apatinib at 500 mg/day under a compassionate access programme. Primary end-point was objective response rate (ORR; RECIST v1.1). Kaplan-meier method was used to estimate progression-free survival (PFS) and overall survival (OS). Toxicity was assessed by CTCAE v4.0. 82.9% (29 of 35) of patients had poly-metastatic rmNPC. All patients, except five, were platinum-refractory; 37.1% (13 of 35) received ≥ 2 lines. Median number of apatinib cycles was 4.0 (IQR: 2.0-8.0). ORR was 31.4% (11 of 35 [95% CI: 16.9-49.3]) and disease control rate was 74.3% (26 of 35 [95% CI: 56.7-87.5]); 11 (31.4%) and 4 (11.4%) patients demonstrated response for ≥ 6 and ≥ 12 months, respectively. Median PFS and OS was 3.9 (95% CI: 3.1-5.5) months and 5.8 (95% CI: 4.5-8.0) months, respectively. Among the ≥ 12-month responders, all patients had pre-apatinib EBV DNA titer of <700 (range: 353-622) copies/ml; this was consistent with the association of PFS with pre-apatinib EBV DNA titer (adjusted HR 3.364 [95% CI: 1.428-7.923] for ≥ 4000 copies/ml, P = 0.006). 42.9% (15 of 35) of patients required dose reduction. Nonetheless, only five (14.3%) patients suffered from G3 toxicities (two haematological, one hypertension, one hand-foot syndrome and one elevated aminotransferases). Our data suggests potential efficacy of apatinib in rmNPC patients. Although incidence of severe toxicities was low, dose modification was required in 42.9% of patients.
Pubmed PDF WebXavier León, César Orús, María Casasayas, Eduard Neumann, Anna Holgado, Miquel Quer
Publication date 14-02-2021
Over the last few decades, there have been changes in the diagnostic capabilities and treatment of head and neck squamous cell carcinoma (HNSCC) patients. However, the impact of these changes on the ultimate survival of patients remains unclear. The objective of this study was to analyze the changes in disease-specific survival of patients with HNSCC treated consecutively over a period of 30 years in a tertiary center. We carried out a retrospective analysis of 5,206 carcinomas located in the oral cavity, nasopharynx, oropharynx, hypopharynx, larynx or with metastatic squamous cell carcinoma without a known primary tumor treated in our center during the period 1985-2016. The overall and disease-specific survival was analyzed according to the year of diagnosis of the tumor. There was a significant trend towards an increase in disease-specific survival over the study period, with an average survival gain of 0.28% per year, which means an increase in 5-year disease-specific survival values from about 63.5% during the initial years of the study to 72% during the final years. Patients who had a greater increase in survival were those with primary tumors located in the rhino-oro-hypopharynx, with advanced tumors (stages III-IV) and treated with radiotherapy or chemoradiotherapy. This increase in disease-specific survival did not translate into overall survival. Over the last 30 years we have observed a significant increase in the disease-specific survival of the patients with HNSCC, with an average increase of 0.28% per year in the 5-year specific-disease survival.
Pubmed PDF WebMei Lin, Qi Yang, Rui You, Xiong Zou, Chong-yang Duan, You-ping Liu, Pei-yu Huang, Yu-long Xie, Zhi-qiang Wang, Ting Liu, Si-Yuan Chen, Yi-jun Hua, Ming-yuan Chen
Publication date 21-02-2021
The current metastatic category (M) of nasopharyngeal carcinoma (NPC) is a "catch-all" category, we previously successfully established a M1 subdivision system based on prognostic metastatic characteristics in epidemic areas. We aimed to figure out metastatic characteristics associated with survival outcomes of NPC in non-epidemic areas.
A total of 428 newly diagnosed de novo metastatic NPC patients from 2010 to 2016 were analyzed from the population-based Surveillance, Epidemiology, and End Results program. Cox proportional hazard ratios (HRs) were used to identify independent prognostic factors for survival.
The most frequently involved metastatic locations were the bones (53.04%), the lungs (36.68%), the livers (29.21%) and the distant lymph nodes (24.07%). Univariate analysis indicated that bone involvement (HR = 1.39, 95% CI = 1.09-1.77), liver involvement (HR = 1.44, 95% CI = 1.12-1.85) and multiple metastatic locations (HR = 1.32, 95% CI = 1.04-1.67) were negative prognostic factors of overall survival (OS) for patients with synchronous metastasis.
We established a new M1 subdivision system based on metastatic characteristics: M1a, without bone and liver involvement; M1b, single bone or liver involvement; M1c, multiple metastatic locations including bone and/or liver. Multivariate analysis confirmed that our new subcategories were associated with significantly different OS (M1b vs M1a: HR = 1.54, 95% CI = 1.11-2.16; M1c vs M1a: HR = 2.03, 95% CI = 1.47-2.78).
Synchronous metastatic NPC patients with multiple metastatic locations involved bone and/or liver were prone to suffer from dismal OS and might need more attentions for selection of treatment modality.
Anna Viganò, Francesca De Felice, Nicola Alessandro Iacovelli, Daniela Alterio, Nadia Facchinetti, Olga Oneta, Almalina Bacigalupo, Elena Tornari, Stefano Ursino, Fabiola Paiar, Orietta Caspiani, Alessia Di Rito, Daniela Musio, Paolo Bossi, Patrizia Steca, Barbara Alicja Jereczek-Fossa, Andrea Greco, Ester Orlandi
Publication date 08-02-2021
Head and neck cancer (HNC) patients are likely to develop severe side effects, which may persist long after the end of treatment and may be responsible for decrease patient's quality of life. The M.
D. Anderson Symptom Inventory- Head and Neck Module (MDASI-HN) is a questionnaire developed to detect patient's symptom burden. To conduct an Italian language psychometric validation of MDASI-HN among Italian HNC patients on behalf of the Italian Association of Radiotherapy and Clinical Oncology (AIRO) Head and Neck Working Group.
To assess construct validity, it was performed a confirmatory factor analysis (CFA) with both a five-factor solution and three-factor solution, which were compared by a chi-square difference test. The concurrent validity was evaluated by the correlation with EORTC QLQ-C30 and HN35, and it was also assessed known-group validity. The internal consistency was tested using Cronbach's alpha coefficient.
In total 166 patients (71.7% male) were included in the study, most of patients (56.2%) had an oropharynx cancer and received definitive chemoradiotherapy (51.2%). The chi-square difference test was significant and indicated that the five-factor solution fits the data better than the other one. Regarding CFA, all items had a significant saturation with their respective factors; besides, significant and strong correlations were found among factors. Most of the correlations between MDASI-HN factors and EORTC QLQ-C30 and HN35 were significant. It was found a good internal consistency.
The MDASI-HN is a valid, short, and easy patient-reported outcome questionnaire which would be useful and efficient in clinical setting.
J.M. Price, C.M. West, H.B. Mistry, G. Betts, P. Bishop, J. Kennedy, L. Dixon, J.J. Homer, K.P. Garcez, L.W. Lee, A. McPartlin, A.J. Sykes, D.J. Thomson
Publication date 07-02-2021
For oropharynx squamous cell carcinoma (OPSCC) this study aimed to: (i) compare 5-year overall survival (OS) stratification by AJCC/UICC TNM versions 7 (TNMv7) and 8 (TNMv8), (ii) determine whether changes to T and N stage groupings improve prognostication and (iii) develop and validate a model incorporating additional clinical characteristics to improve 5-year OS prediction. All OPSCC treated with curative-intent at our institution between 2011 and 2017 were included. The primary endpoint was 5-year OS. Survival curves were produced for TNMv7 and TNMv8. A three-way interaction between T, N stage and p16 status was evaluated for improved prognostication. Cox proportional hazards modelling was used to derive a new predictive model. Of 750 OPSCC cases, 574 (77%) were p16-positive. TNMv8 was more prognostic than TNMv7 (concordance probability estimate [CPE] ± SE = 0.72 ± 0.02 vs 0.53 ± 0.02). For p16-positive disease, TNMv8 discriminated stages II vs I (HR 2.32, 95% CI 1.47-3.67) and III vs II (HR 1.75, 95% CI 1.13-2.72). For p16-negative disease, TNMv7 and TNMv8 demonstrated poor hazard discrimination. Different T, N stage and p16-status combinations did not improve prognostication after adjusting for other factors (CPE = 0.79 vs 0.79, p = 0.998). A model for p16-positive and p16-negative OPSCC including additional clinical characteristics improved 5-year OS prediction beyond TNMv8 (c-index 0.76 ± 0.02). TNMv8 is superior to TNMv7 for p16-positive OPSCC, but both performed poorly for p16-negative disease. A novel model incorporating additional clinical characteristics improved 5-year OS prediction for both p16-positive and p16-negative disease.
Pubmed PDF WebLuigi Lorini, Laura Ardighieri, Anna Bozzola, Chiara Romani, Eliana Bignotti, Michela Buglione, Andrea Guerini, Davide Lombardi, Alberto Deganello, Michele Tomasoni, Sara Anna Bonini, Sandra Sigala, Davide Farina, Marco Ravanelli, Paolo Bossi
Publication date 13-02-2021
Adenoid cystic carcinoma (ACC) is a rare tumor, usually arising in the salivary gland, accounting for 1% of all head and neck cancers. ACC may have a long-term poor prognosis, as about 40% of radically treated patients will recur locoregionally and up to 60% will develop distant metastasis. Factors influencing risk of recurrence have been well studied, but few data exist about prognostic factors in Recurrent/Metastatic (RM) setting. Moreover, treatment of RM ACC is often a challenge for clinicians, in the context of a rare disease, which may have an indolent clinical behavior or less frequently a quicker growth and with a paucity of available clinical trials. This review critically analyzes pathological and molecular prognostic factors in RM ACC and make an overview on actual therapeutic choices and future direction of therapy. Recognized prognostic factors in RM ACC are the presence and site of distant metastasis (lung vs other), the presence of nodal metastasis and of extranodal extension, skull base recurrence, disease free interval, lymphovascular invasion, solid histotypes and grading of disease, and the presence of mutation of NOTCH1 family, PI3K, and TP53. Due to disappointing results with chemotherapy, new approaches are under study, also on the basis of biomolecular research. Ongoing clinical trials are evaluating treatment targeting MYB and NOTCH1 alterations, immunotherapy or combination of targeted treatments and immune checkpoint inhibitors.
Pubmed PDF WebFabrício dos Santos Menezes, Gisele Aparecida Fernandes, José Leopoldo Ferreira Antunes, Luisa Lina Villa, Tatiana Natasha Toporcov
Publication date 10-02-2021
In head and neck cancer (HNC), some subsites are associated with human papillomavirus (HPV) infection, whereas others are unrelated. Although studies have demonstrated the heterogeneity of HPV prevalence worldwide, its impacts on incidence trends in HNC are unknown. This systematic review examined the incidence trends for HPV-related HNC subsites, exploring patterns by geographic region, age group, sex, and race/ethnicity. We searched for publications on Pub Med, Embase, and Scopus. Eligible articles included population-based studies that analyzed incidence trends for subsites classified as a proxy for HPV infection in HNC (hereafter referred to as HPV-related subsites). We retrieved 3,948 non-duplicate records, of which 31 were eligible articles, representing 18 countries and spanning almost fifty years. Overall, the incidence of HPV-related HNC subsites rose, while most of the HPV-unrelated subsites declined or remained stable. For HPV-related HNC subsites, incidence trends increased regardless of age group, highlighting a distinct global pattern between sexes. Also, similar peaks in increased risk were observed in recent cohorts from both Australia and the United States. There is a dramatic shift in the global trends of HNCs, characterized by the emerging burden in HNC for HPV-related subsites.
Pubmed PDF WebKate Chatfield-Reed, Veronique P. Roche, Quintin Pan
Publication date 15-02-2021
High-risk human papillomavirus (HPV) is an etiologic factor in a spectrum of squamous cell carcinomas including anal, cervical, and oropharyngeal. HPV cell free DNA (cfDNA) is shed from the primary tumor into systemic circulation and can be detected using several platforms including quantitative PCR, digital droplet PCR, or next generation sequencing. Levels of HPV cfDNA at time of initial presentation is associated with known poor prognostic clinicopathologic variables, such as advanced stage and, locoregional and distant metastases. Moreover, longitudinal sampling revealed that persistent or increasing HPV cfDNA levels are indicative of treatment relapse and, in some studies, HPV cfDNA detection predicted treatment failures prior to routine post-treatment clinical imaging. A liquid biopsy platform using HPV cfDNA offers unique advantages over traditional approaches and may have clinical utility for detection of minimum residual disease, treatment response, and disease progression in patients with HPV+ cancers.
Pubmed PDF WebDouglas Adkins, Jessica Ley, Omar Atiq, Steven Powell, William C. Spanos, Mark Gitau, Caron Rigden, Kevin Palka, Jingxia Liu, Peter Oppelt
Publication date 07-02-2021
Macropinocytosis promotes internalization of albumin into cells to serve as a nutrient supply and is constitutively driven by signaling pathways frequently hyperactivated in head and neck squamous-cell carcinoma (HNSCC). In this way, drugs bound to albumin may selectively target HNSCC. nab-paclitaxel is a nanoparticle albumin-bound formulation of paclitaxel that improves drug delivery into tumor compared to paclitaxel. The primary aim of this single-arm, multicenter, phase 2 trial was to determine if nab-paclitaxel, cetuximab, and carboplatin (CACTUX regimen) would result in longer progression-free survival (PFS) than the historical regimen (EXTREME: 5-fluorouracil, cetuximab, and a platinum). Patients with untreated recurrent or metastatic HNSCC received six, three-week cycles of nab-paclitaxel, cetuximab, and carboplatin, followed by maintenance nab-paclitaxel and cetuximab until progression. We hypothesized the median PFS with CACTUX would be 35% longer than with EXTREME (corresponding to 7.6 vs 5.6 months; power 0.80, α = 0.05, one-sided test, n = 70). Secondary outcomes included objective response rate (ORR) and overall survival (OS). Seventy-four patients enrolled into the trial; seventy were evaluable. The median PFS was 6.1 months (95% CI, 4.1-7.4). The ORR was 60%. Median follow-up was 18 months (IQR: 4.7-23). The median OS was 17.8 months (95% CI, 8.5-21.7) for all patients, and 19.8 months (95% CI, 10.9-22.0) for human papillomavirus (HPV)-related oropharynx SCC and 14.0 months (95% CI, 4.6-23.3) for HPV-unrelated HNSCC. Among patients with recurrent or metastatic HNSCC, CACTUX did not result in a longer PFS than historical EXTREME. However, CACTUX did result in a more favorable ORR and OS.
Pubmed PDF WebLauren M. North, Erin Harvey, Brigitte Vanle, Aditya Shreenivas, Monica Shukla, Stuart Wong, Musaddiq Awan, Joseph Zenga
Publication date 23-02-2021
Chirom Amit Singh, Pirabu Sakthivel, Vimmi Gautam, Suresh Mani, Rajeev Kumar
Publication date 23-02-2021
Biswajoy Ghosh, Avishek Bhandari, Mousumi Mandal, Ranjan Rashmi Paul, Mousumi Pal, Pabitra Mitra, Jyotirmoy Chatterjee
Publication date 21-02-2021
John Lennon Silva Cunha, Saygo Tomo, Carolina Peres Mota, Ivan José Correia Neto, Sílvia Ferreira de Sousa, Jorge Esquiche León, Ricardo Luiz Cavalcanti de Albuquerque-Júnior
Publication date 20-02-2021
Pleomorphic lipomas are extremely rare in the oral cavity. Due to the significant overlap of morphological findings with several benign and malignant soft tissue tumors, especially in the absence of adipocytes, the diagnosis is challenging. We reported the clinicopathological and immunohistochemical features of an uncommon case of a fat-free variant of pleomorphic lipoma in a 48-year-old female presenting clinically as a painless nodule on the buccal mucosa. Microscopically, the lesion showed atypical spindle cells, numerous floret-like giant multinucleated cells, and abundant ropey collagen fibers bundles. Immunohistochemistry showed strong positivity for vimentin and CD34. Mast cell tryptase highlighted numerous mast cells distributed throughout all tumor stroma. S-100 protein, pan-cytokeratin, desmin, α-SMA, EMA, CD68, STAT6, Bcl-2, MDM2, and CDK4 were negative. Conservative surgical excision was carried out, and no recurrence was observed after 13 months of follow-up. Careful histopathological and immunohistochemistry analysis of these lesions is recommended to ensure the correct diagnosis and provide adequate management through a conservative surgical approach. To the best of our knowledge, this is the second case of fat-free pleomorphic lipoma in the oral cavity.
Pubmed PDF WebSachin C. Sarode, Gargi S. Sarode, Nilesh Kumar Sharma, Shankargouda Patil
Publication date 20-02-2021
Indistinct basement membrane due to inflammation always poses a problem to the pathologists for commenting on micro-invasive squamous cell carcinoma. In such a situation, even a special stain would not be able to correctly demonstrate the basement membrane, which is necessary for estimating the depth of invasion. In this paper, we have proposed a novel fluorescent microscopy assisted visualization of basement membrane in such difficult situations. To further validate this approach, we then retrospectively investigated twenty such cases under a fluorescent microscope and could able to repeat the same result. As routine hematoxylin and eosin stained sections are required for evaluation, it is technically less demanding and less time-consuming.
Pubmed PDF WebDaniel L. Faden, Connor J. OBoyle, Derrick T. Lin, Daniel G. Deschler, Kevin S. Emerick, Mark A. Varvares, William C. Faquin, Peter M. Sadow, Jeremy D. Richmon
Publication date 20-02-2021
Yash P. Merchant, Akshay Kudpaje, Vishal U.S. Rao
Publication date 18-02-2021
Oreste Gallo, Luca Giovanni Locatello
Publication date 15-02-2021
Guna Shekhar Madiraju
Publication date 14-02-2021
Gnathic osteosarcoma is a rare malignant mesenchymal neoplasm showing evidence of osteoid matrix formation. Clinical behaviour and radiological appearances overlap with benign osseous lesions and are prone to misdiagnosis. Early diagnosis of osteosarcoma plays a crucial role in the treatment plan and prognosis. Herein a rare case of parosteal osteosarcoma of fibroblastic histologic subtype affecting the angle of the mandible in a 12-year-old female is presented.
Pubmed PDF WebBipin T. Varghese, G.M. Divya, Deepak Janardhan, Shaji Thomas
Publication date 13-02-2021
Lísia Daltro Borges Alves, Andreia Cristina de Melo, Luiz Henrique de Lima Araujo, Leandro Souza Thiago, Isabella dos Santos Guimarães, Priscila Valverde Fernandes, Elizangela Marques Rodrigues, Fernando Luiz Dias, Héliton Spindola Antunes, Ana Lucia Amaral Eisenberg, Daniel Cohen Goldemberg
Publication date 13-02-2021
This study aim was to review cases of acinic cell carcinoma (the main differential diagnosis of secretory carcinoma) that were diagnosed and treated at the National Cancer Institute of Brazil (INCA) between 1996 and 2016. The primary objective was to identify underdiagnosed cases of secretory carcinoma via a clinical, immunopathological and molecular reassessment. This is a cross sectional study, with retrospective data collection from medical records and histological specimen review, with staining for periodic acid-Schiff (PAS) and PAS with diastase, immunohistochemistry for S-100, mammaglobin, and DOG-1, and droplet digital RT-PCR for ETV6-NTRK3. The Research Ethics Committee approved this study, and the patients allowed their participation through informed consent. Eighty-three cases of acinic cell carcinoma were diagnosed and treated in the specified period at INCA, of which, seven had their diagnosis changed to secretory carcinoma. The present study adds seven cases of secretory carcinoma to the literature, contributing to a better understanding of the epidemiological, histological, immunohistochemical and molecular characteristics of this recently described tumor. Also, the use of a comprehensive diagnostic approach, including immunohistochemical and molecular methods, along with classical morphological studies, allowed the reclassification of acinic cell carcinoma to secretory carcinoma.
Pubmed PDF WebK. Brust, P. Nogal, D. Miętkiewska-Leszniewska, K. Iwanik, Z. Krasiński, M. Wierzbicka
Publication date 14-02-2021
Angiosarcoma is a malignancy of endothelial tumor and represents 1-2% of all soft tissue sarcomas, uncommonly found in the head and neck region. The etiology is not clear but there are definite risk factors including chronic lymphoedema, history of radiation, environmental carcinogens and certain familial syndromes. Presented here is a case of a patient treated due to the skull base trauma and diagnosed with this type of tumor.
Pubmed PDF WebB. Guruchannabasavaiah, Irappa V. Madabhavi, D.B. Avinash, R. Aravindan, Praveen Devarabhavi, Pradeepa H. Dakappa
Publication date 12-02-2021
Paraganglioma is a rare type of neuroendocrine tumor with the ability to secrete neuropeptide and catecholamines in excess. Sympathetic hyperactivity, severe persistent headache and hypertension is the most common clinical presentation of paraganglioma similar to pheocromocytoma. Case report We reported a case of 19 year old girl with severe headache and hypertension, from past 6 month. On further imaging evaluation for the headache, the computed tomography of the abdomen plus pelvis was suggestive of left pre para aortic paraganglioma measuring of 3.4 cm in diameter. Surgical excision of mass was done. Histopathological examination of surgical specimen was consistent with the diagnosis of paraganglioma. Patient is on regular follow up without any subjective or objective evidence of the disease. Retroperitoneal paraganglioma may be one of the causes for commonly occurring symptomatic headache, which is benign in nature, but possibility of transformation of malignant paraganglioma can occur. The surgical excision of mass is the treatment of choice.
Pubmed PDF WebRui Lu, Gang Zhou
Publication date 10-02-2021
Anuraag S. Parikh, Stephen Y. Kang
Publication date 06-02-2021
Wei Ning Jiang, Robert Olson
Publication date 06-02-2021
Abhinav Thaduri, Adity Bansal, Michael Leonard Anthony, Manishi L. Narayan, Ashi Chug, Pankaj Kumar Garg
Publication date 03-02-2021
Abhinav Thaduri, Lisa Chadha, Dharma Ram Poonia, K.S. Rajkumar, Pankaj K. Garg
Publication date 31-01-2021
Hui-hui Ma, Dong-sheng Chen, Si Li, Ming-zhe Xiao, Chuang Qi
Publication date 31-01-2021
Emrullah Yilmaz, Michelle A. Ozbun, Gregory N. Gan
Publication date 30-01-2021
Gargi S. Sarode, Sachin C. Sarode, Namrata Sengupta, Nilesh Kumar Sharma, Shankargouda Patil
Publication date 28-01-2021
Clinical, histological and molecular alterations observed at surgical margins could be regarded as predictive markers of malignant transformation. However, there are contrasting views on usefulness of oral epithelial dysplasia (OED) in predicting malignant transformation. In this regard, investigation of OED status at surgical margins could give an interesting perspective to this notion. We searched the reputed databases to retrieve the original research articles wherein the OED status was investigated at the mucosal surgical margins of oral squamous cell carcinoma (OSCC). Intriguingly, in all the studies, number of cases in 'no dysplasia' category was higher than other grades of dysplasia. In our institutional experience of 92 cases of OSCC, 75 (82%) cases showed no evidence of dysplasia at surgical margins. Thus, we conclude that dysplasia status at surgical margins does not support the OED as potential marker of malignant transformation.
Pubmed PDF WebAlexis Nguyen, Misako Nagasaka
Publication date 26-01-2021
We here present an unusual case in which a patient with metastatic HNSCC was enrolled in a number of clinical trials, but was never exposed to platinum or taxane therapy, who fortunately continues to show response after carboplatin and paclitaxel, given to her as her 6th line of therapy for metastatic disease. While some non-chemotherapy based clinical trials may appear attractive to both the clinicians and the patients, and although it may be tempting to offer exciting trials when the patient "meets the eligibility criteria", in some cases, it may be beneficial to go back and re-consider standard chemotherapy.
Pubmed PDF WebAlok Thakar, Pirabu Sakthivel, Kingston Samy, Smriti Panda
Publication date 25-01-2021
Alison José Martelli, Renato Assis Machado, Wilson Medeiros Pereira, Denise Maria M. Silveira, Danyel Elias da Cruz Perez, Hercílio Martelli Júnior
Publication date 27-01-2021
K Devaraja
Publication date 23-01-2021
Lei Zhou
Publication date 21-01-2021
Pablo Varela-Centelles, Juan Seoane, Arturo Bilbao, Juan Seoane-Romero
Publication date 25-01-2021
C. Moreira, T. Corrales
Publication date 18-01-2021
A patient suffering from metastatic pancreatobiliary adenocarcinoma was referred to our hospital's stomatology department after a rapidly progressing swelling in the right mandibular angle, trismus and preauricular pain of 3-month duration. A mandible CT scan showed extensive bone rarefaction and a thickening of the contiguous soft tissues that involved the medial masseter and pterygoid muscle. The morphological findings and immunohistochemical profile were compatible with bone metastasis from pancreatic adenocarcinoma. Therefore, palliative treatment was proposed to the patient. Pancreatic cancer metastases to the oral cavity are extremely rare and characterized by its poor prognosis. Herein we describe the ninth case of metastatic spread to the jaw which is also remarkably the longest surviving reported case up to date.
Pubmed PDF WebStergios Doumas, Rodopi Koursoumi, Jagtar Dhanda, Christian Surwald, Dimitrios Kanoutos, Vassileios Lachanas
Publication date 30-01-2021