Sentinel node biopsy for squamous cell carcinoma of the oral cavity and oropharynx: A diagnostic meta-analysis
Tim M. Govers
Gerjon Hannink
Matthias A.W. Merkx
Robert P. Takes
Maroeska M. Rovers
Received 24 January 2013; received in revised form 16 April 2013; accepted 19 April 2013. published online 15 May 2013.
Summary
Background
The aim of the study was to systematically assess the accuracy of a sentinel lymph node biopsy (SLNB) in cT1/T2N0 oral cavity and oropharyngeal squamous cell carcinoma patients.
Methods
We searched electronic databases, including EMBASE and MEDLINE (Pubmed) up to November 7 2012, by combining oral cancer keywords with sentinel node biopsy keywords. We included diagnostic accuracy studies which used neck dissection as a reference test for the sentinel node biopsy. Study characteristics and measures of accuracy were extracted. Diagnostic accuracy was calculated from 2×2 tables.
Results
21 Studies (847 patients) could be included. Most of these patients had oral cavity squamous cell carcinoma (OCSCC). The pooled data showed an overall sensitivity of 0.93 [95% CI 0.90–0.95]. Subgroup analysis showed no significant differences in subgroups.
Conclusion
The high sensitivity of SLNB supports a role in the diagnostic work-up of OCSCC.
© 2013 Elsevier Ltd. All rights reserved.
Oral Oncology
Volume 49, Issue 8 , Pages 733-737, August 20133
p53-based therapeutics for head and neck squamous cell carcinoma
Patrick Tassone
Matthew Old
Theodoros N. Teknos
Quintin Pan
Received 5 March 2013; received in revised form 15 March 2013; accepted 19 March 2013. published online 29 April 2013.
Summary
Inactivation of the tumor suppressor p53 is a pathogenetic event in the development of head and neck squamous cell carcinoma (HNSCC). In the absence of functional wildtype p53, HNSCC cells have increased resistance to standard chemotherapeutics and radiation. Numerous approaches to restore p53 function in cancer cells have been developed over the past several decades. This review article focuses on viral approaches to deliver wildtype p53 to HNSCC cells, a designer virus that selectively eliminates mutant p53 HNSCC cells, and chemical approaches to reactivate p53 function in HNSCC cells. These promising studies provide evidence that p53 therapeutics may prove useful alone or in combination with conventional chemotherapy and/or radiation for the management of HNSCC patients.
© 2013 Elsevier Ltd. All rights reserved.
Oral Oncology
Volume 49, Issue 8 , Pages 738-746, August 20134
The cancer stem cell hypothesis applied to oral carcinoma
M.A. González-Moles
C. Scully
I. Ruiz-Ávila
J.J. Plaza-Campillo
Received 12 March 2013; received in revised form 9 April 2013; accepted 9 April 2013. published online 03 May 2013.
Summary
It has been proposed that the development of tumors is based exclusively on the activity of cancer stem cells (CSCs) leading to a new model of carcinogenesis, the CSC hypothesis, in opposition to the conventional model of clonal evolution. The new model may help to explain the high mortality of oral cancer, unchanged over the past decades, the low response to treatment and the tendency of oral squamous cell carcinoma (OSCC) patients to develop multiple tumors. However, a more profound understanding of the molecular pathways involved in maintaining the stem cell (SC) state and of their alterations is required to elucidate the mechanisms underlying the development of tumors and metastatic spread, but research into SC biopathology is hampered by the lack of specific markers for identifying SCs and CSCs in tissues and for establishing topographic relationships with their lineage. We review current knowledge on stem cells in relation to oral cancer, including their possible origins, focusing on the CSC hypothesis of oral tumorigenesis and attempts being made to identify oral stem cells.
© 2013 Elsevier Ltd. All rights reserved.
Oral Oncology
Volume 49, Issue 8 , Pages 747-752, August 20135
Induction chemotherapy for squamous cell head and neck cancer: A neverending story?
Marco Benasso
Received 6 February 2013; received in revised form 17 April 2013; accepted 19 April 2013. published online 17 May 2013.
Summary
Induction chemotherapy prior to planned definitive local therapy for head and neck squamous cell carcinoma has been studied for at least three decades but the debate on its role is still open. Recent landmark studies, including those presented at outstanding meetings and those still ongoing on induction chemotherapy in different clinical situations, are critically reviewed. Data confirm that a docetaxel, cisplatin and 5-fluorouracil (TPF) based induction chemotherapy may be considered in clinical practice as one of the possible options when a larynx preservation strategy is attempted. On the contrary, current data do not support the use of induction chemotherapy before a planned surgical intervention for advanced oral cavity and oropharyngeal tumors. Currently, for patients with locoregionally advanced unresectable disease, concomitant chemo-radiation remains the standard of care in waiting for results of the few ongoing studies that hopefully will clarify the role of induction TPF before either concomitant chemo-radiation or bio-radiation.
© 2013 Elsevier Ltd. All rights reserved.
Oral Oncology
Volume 49, Issue 8 , Pages 753-760, August 20136
Body image in patients with head and neck cancer: A review of the literature
Bethany Andrews Rhoten
Sheila H. Ridner<a href="mailto:sheila.ridner
Received 4 March 2013; received in revised form 13 April 2013; accepted 17 April 2013. published online 16 May 2013.
Summary
Objectives
Patients with head and neck cancer have a high potential for body image disturbance due to highly visible disfigurement resulting from both the primary cancer and its treatment. The purpose of this review is to examine the conceptual framework for understanding body image in patients treated for head and neck cancer, present the current state of the science, discuss measurement issues, and identify areas for future investigation. A novel hypothetical model based on ongoing work is proposed, and it asserts that head and neck cancer therapy results in two main tumor/treatment related physical effects: (1) disfigurement and (2) dysfunction. In this model, personal, social and environmental factors moderate the effect of dysfunction and disfigurement on body image.
Results
A search of the empirical literature revealed a paucity of data on body image in head and neck cancers including a lack of longitudinal data as well as a lack of data on the relationship between body image disturbance and other psychosocial variables such as depression, anxiety, and social isolation over the course of treatment and throughout recovery. Additionally, the need for measurement tools specifically developed for the assessment of body image in head and neck cancer patients was identified.
Conclusion
Prospective longitudinal studies that define the trajectory of body image issues and the mediating and moderating factors associated with body image will allow researchers to design targeted interventions to limit body image disturbance and thereby improve quality of life in patients with head and neck cancer.
© 2013 Elsevier Ltd. All rights reserved.
Oral Oncology
Volume 49, Issue 8 , Pages 761-770, August 20137
Interleukin-8 as a modulator of response to bevacizumab in preclinical models of head and neck squamous cell carcinoma
Rekha Gyanchandani
Daisuke Sano
Marcus V. Ortega Alves
Jonah D. Klein
Beth A. Knapick
Sanders Oh
Jeffrey N. Myers
Seungwon Kim
Received 17 December 2012; received in revised form 27 February 2013; accepted 24 March 2013. published online 26 April 2013.
Summary
Objectives
Bevacizumab, a monoclonal antibody to VEGF-A, is under active clinical evaluation in head and neck squamous cell carcinoma (HNSCC) and appears to be a promising therapy in at least a subset of patients. However, there are no reliable predictive biomarkers to identify those patients most likely to benefit. In this study, we assessed the efficacy of bevacizumab in HNSCC xenograft models to characterize escape mechanisms underlying intrinsic resistance and identify potential biomarkers of drug response.
Materials and methods
We evaluated the angiogenic profile of HNSCC cells from sensitive and resistant cell lines using antibody array. We further examined the role of interleukin-8 (IL-8) in contributing to resistance both in vitro and in vivo, using a loss- and gain-of-function approach.
Results
Angiogenic profiling indicated that resistant cells expressed higher levels of proangiogenic factors including IL-8, interleukin-1α (IL-1α), vascular endothelial growth factor (VEGF), fibroblast growth factor-a (FGF-a), and tumor necrosis factor-α (TNF-α). IL-8 was the most differentially expressed protein. IL-8 signaling compensated for VEGF inhibition in endothelial cells. Downregulation of IL-8 resulted in sensitization of resistant tumors to bevacizumab by disrupting angiogenesis and enhancing endothelial cell apoptosis. Overexpression of IL-8 in sensitive tumors conferred resistance to bevacizumab. Serum analysis of HNSCC patients treated with a bevacizumab-containing regime revealed high baseline IL-8 levels in a subset of patients refractory to treatment but not in responders.
Conclusions
These results implicate IL-8 in mediating intrinsic resistance to bevacizumab in HNSCC. Hence, co-targeting of VEGF and IL-8 may help overcome resistance and enhance therapeutic efficacy.
© 2013 Elsevier Ltd. All rights reserved.
Oral Oncology
Volume 49, Issue 8 , Pages 771-777, August 20138
Management of the N0 neck in early stage oral squamous cell cancer: A modeling study of the cost-effectiveness
Tim M. Govers
Robert P. Takes
M. Baris Karakullukcu
Gerjon Hannink
Matthias A.W. Merkx
Janneke P.C. Grutters
Maroeska M. Rovers
Received 15 November 2012; received in revised form 2 April 2013; accepted 2 May 2013. published online 03 June 2013.
Summary
Objectives
To assess the cost-effectiveness of five strategies for diagnosing and treating cT1–2N0 oral squamous cell cancer.
Materials and methods
A Markov decision analytic model was used to evaluate the cost-effectiveness of (1) elective neck dissection (END), (2) watchful waiting (WW), (3) gene expression profiling (GEP) followed by neck dissection (ND) or WW, (4) sentinel lymph node (SLN) procedure followed by ND or WW, and (5) GEP and SLN (for positive GEP) followed by ND or WW. Uncertainty was addressed using one-way and probabilistic sensitivity analyses.
Results
Base-case analysis showed that SLN procedure followed by ND or WW was the most effective and most cost effective strategy. Compared with direct END the incremental cost effectiveness ratio was €3356 per QALY gained. Uncertainty analysis showed that the model was sensitive to changes in assumed occult metastases incidence and utility values. SLN was found to have the highest probability (66%) of being cost-effective of the five strategies, at a willingness to pay of €80,000 per QALY.
Conclusions
Given the current evidence and costs the SLN procedure followed by ND or WW appears to be the most cost effective strategy for diagnosing and treating oral squamous cell cancer patients. Our model provides the foundation for future diagnostic and therapeutic research in this field and shows that further information on quality of life in this population is highly valuable.
© 2013 Elsevier Ltd. All rights reserved.
Oral Oncology
Volume 49, Issue 8 , Pages 778-786, August 20139
Atorvastatin inhibits RhoC function and limits head and neck cancer metastasis
Mozaffarul Islam
Smita Sharma
Bhavna Kumar
Theodoros N. Teknos
Received 14 February 2013; received in revised form 29 March 2013; accepted 9 April 2013. published online 06 May 2013.
Summary
Objective
RhoC oncogene is a well characterized marker of metastasis in a majority of invasive cancers, including HNSCC. Elevated RhoC expression has been found to be associated with distant metastasis. Statins are a class of drugs that are used to reduce cholesterol levels by inhibiting HMG-CoA reductase activity which in turns prevents mevalonate synthesis, which is a precursor for synthesis of cholesterol and prenylation. Interestingly, the proper function of Rho proteins depends on prenylation. Significantly, it has been reported that metastasis in human melanoma can be reduced by atorvastatin which inhibits RhoC activity by preventing its geranylgeranylation. Given that RhoC is a key oncogene involved in metastasis, we hypothesized Atorvastatin can reduce head and neck metastasis by inhibiting RhoC activity.
Methods
In vitro and in vivo studies were carried out to evaluate the ability of Atorvastatin to inhibit RhoC function and HNSCC metastasis. Cell motility, proliferation, cell invasion, and colony formation assays were performed according to the standard protocols.
Results
Atorvastatin treatment significantly reduced the active form of RhoC in vitro and diminished cell motility, invasion, proliferation and colony formation. Importantly, we observed a significant decrease in p-ERK1/2 and p-STAT3 in Atorvastatin treated cell lines. In vivo experiments revealed inhibition of angiogenesis and lung metastases with Atorvastatin therapy.
Conclusions
This study is the first of its kind to establish a potential role of Atorvastatin in head and neck cancer therapy. These findings suggest that Atorvastatin can be a potential low risk adjuvant therapy to minimize metastases in aggressive forms of HNSCC.
© 2013 Elsevier Ltd. All rights reserved.
Oral Oncology
Volume 49, Issue 8 , Pages 787-795, August 201310
CD44 and SSEA-4 positive cells in an oral cancer cell line HSC-4 possess cancer stem-like cell characteristics
Zenko Noto
Toshiko Yoshida
Motonori Okabe
Chika Koike
Moustafa Fathy
Hiroaki Tsuno
Kei Tomihara
Naoya Arai
Makoto Noguchi
Toshio Nikaido
Received 7 November 2012; received in revised form 24 April 2013; accepted 29 April 2013. published online 14 June 2013.
Summary
Background
Cancer may be derived from cancer stem-like cells (CSCs), which are tumor-initiating cells that have properties similar to those of stem cells. Identification and isolation of CSCs needs to be improved further.
Materials and methods
CSCs markers were examined in human oral cancer cell lines by flow cytometry. The stem cell properties of subpopulations expressing different markers were assessed further by in vitro sphere formation assays, expression of stemness genes, drug resistance assays, and the ability to form tumors in nude mice.
Results
We demonstrated that CSCs could be isolated by the cell surface markers CD44 and stage-specific embryonic antigen-4 (SSEA-4). CD44+SSEA-4+ cells exhibited cancer stem-like properties, including extensive self-renewal into the bulk of cancer cells. In vivo xenograft experiments indicated that CD44+SSEA-4+ cells exhibit the highest tumorigenic capacity compared with the remaining subpopulations and parental cells. Double-positive cells for CD44 and SSEA-4 exhibited preferential expression of some stemness genes and were more resistant to the anticancer drugs, cisplatin and 5-fluorouracil (5-FU). In addition, cells expressing CD44 and SSEA-4 were detected in all tumor specimens analyzed, while coexpression of CD44 and SSEA-4 was not detectable in normal oral mucosa.
Conclusion
Our findings suggest that CD44+SSEA-4+ cells exhibit the characteristics of CSCs in oral squamous cell carcinoma and provide a target for the development of more effective therapies.
© 2013 Elsevier Ltd. All rights reserved.
Oral Oncology
Volume 49, Issue 8 , Pages 796-801, August 201311
Increased expression of USP22 is associated with disease progression and patient prognosis of salivary duct carcinoma
Songlin Piao
Jie Ma
Wei Wang
Yanlong Liu
Minghui Zhang
Hongying Chen
Feng Guo
Bin Zhang
Fulin Guo
Received 14 November 2012; received in revised form 27 March 2013; accepted 31 March 2013. published online 13 May 2013.
Summary
Objectives
Ubiquitin-specific protease 22 (USP22) could exhibit a critical function in pathological processes, including oncogenesis and cell cycle progression. This study examines the protein expression of USP22 in salivary duct carcinoma (SDC) in association with patient survival and other clinicopathologic parameters.
Materials and Methods
Quantitative RT-PCR and immunohistochemistry (IHC) were used to determine the expression of USP22 protein in 44 SDCs in comparison with 20 non-cancerous salivary tissues. Furthermore, we analyzed the correlation between the expression of the USP22 protein and various clinicopathologic factors including survival status of patients with SDC.
Results
The incidence of positive USP22 expression was 63.7% in 44 SDC tissues. The mRNA level of USP22 expression in SDC samples was significantly higher than that in non-cancerous salivary tissues (P<0.001), which was consistent with the IHC result (P<0.001). Moreover, statistical analysis showed that positive USP22 expression was positively related to pT classification, pN classification and AJCC stage. Notably, high USP22 expression was significantly associated with shorter overall survival (P=0.023) and disease-specific survival (P=0.019). Multivariate Cox regression analysis revealed that USP22 expression level was an independent prognostic factor for both overall survival (P<0.001) and disease-free survival (P<0.001).
Conclusion
Our results indicate that activation of USP22 correlates with SDC progression and therapy failure. Overexpression of USP22 may contribute to the progression of SDC and thus may serve as a new molecular marker to predict the prognosis of SDC patients.
© 2013 Published by Elsevier Inc.
Oral Oncology
Volume 49, Issue 8 , Pages 802-807, August 201312
Serum levels of chemokine (C-X-C motif) ligand 9 (CXCL9) are associated with tumor progression and treatment outcome in patients with oral cavity squamous cell carcinoma
Kai-Ping Chang
Chih-Ching Wu
Ku-Hao Fang
Chi-Ying Tsai
Yu-Liang Chang
Shiau-Chin Liu
Huang-Kai Kao
Received 28 March 2013; received in revised form 14 May 2013; accepted 15 May 2013. published online 13 June 2013.
Summary
Objectives
The aim of this cohort study was to examine the role of chemokine (C-X-C motif) ligand 9 (CXCL9) on oral cavity squamous cell carcinoma (OSCC).
Methods
Sera from 181 OSCC patients, 231 healthy individuals, and 50 OSCC tumor samples were enrolled. CXCL9 expression in tissue samples was analyzed by quantitative real-time PCR and immunohistochemistry. CXCL9 serum concentrations were measured by enzyme-linked immunosorbent assay. Effects of CXCL9 on OSCC cell function were investigated by cell proliferation assays, trans-well migration/invasion assays, and RNA interference.
Results
CXCL9 expression was significantly higher than for normal epithelium in the tissue samples. CXCL9 serum concentrations were also significantly higher in OSCC patients compared to those in healthy individuals. Serum CXCL9 levels were significantly higher in OSCC patients with higher pT status, pathological overall stages, tumor depths, and positive bone invasion (P=0.033, 0.004, 0.041, and 0.002, respectively). Moreover, OSCC patients with higher CXCL9 levels (>209pg/mL, median level) before treatment had worse prognoses for overall survival and disease-specific survival (P=0.0006 and 0.0009, respectively). Multivariate logistic regression analyses also indicated that higher CXCL9 serum levels were an independent prognostic factor for overall survival and disease-free survival (P=0.003 and 0.004, respectively). The in vitro suppression of CXCL9 expression in SCC25 cells using specific interfering RNAs attenuated cell proliferation, migration and invasiveness.
Conclusions
Our study demonstrated that CXCL9 is associated with tumor burden and aggressiveness of OSCC tumors and serum level of this ligand may be useful as a prognostic indicator.
© 2013 Published by Elsevier Inc.
Oral Oncology
Volume 49, Issue 8 , Pages 808-813, August 201313
The benefit of pretreatment esophageal screening with image-enhanced endoscopy on the survival of patients with hypopharyngeal cancer
Wen-Lun Wang
Jaw-Town Lin<a href="mailto:jawtown
Received 12 February 2013; received in revised form 17 April 2013; accepted 26 April 2013. published online 20 May 2013.
Summary
Background
Synchronous esophageal cancers can suppress the survival of patients with hypopharyngeal cancers. Esophageal screening with the image-enhanced endoscopy may identify more synchronous cancers while there is no evidence to support its benefit on survival.
Methods
A total of 281 and 320 patients were diagnosed with hypopharyngeal cancer before and after the policy of routine esophageal screening. Primary outcome measures were overall survival.
Results
Among those who received screening, 49 patients (49/180, 27.2%) had synchronous esophageal cancers; treatment planning was changed in 42 (23.3%). Before and after the policy, percentages of stage I–II synchronous cancers were 20% (3/15) and 53.1% (26/49), respectively. Adjunctive therapies for synchronous cancers have led to a better survival after the policy than before (P=0.002). The Cox regression model quantified a survival benefit of 29% (95% CI: 11–43%) when adjusting for TNM stage of hypopharyngeal cancer. In post-policy period, the survival was better for those who chose screening than those who did not (HR: 0.57, 95% CI: 0.41–0.79). Among those without screening, there was no difference between the pre- and post-policy periods (HR: 0.96, 95% CI: 0.74–1.26).
Conclusions
Patients with hypopharyngeal cancers may benefit from the esophageal screening with image-enhanced endoscopy through the better detection of early-stage synchronous cancers.
© 2013 Elsevier Ltd. All rights reserved.
Oral Oncology
Volume 49, Issue 8 , Pages 814-817, August 201314
Recurrence patterns and management of oral cavity premalignant lesions
Demetri Arnaoutakis
William Westra<a href="mailto:wwestra
Joseph A. Califano
Received 20 March 2013; received in revised form 22 April 2013; accepted 26 April 2013. published online 20 May 2013.
Summary
Objective
To gain an understanding of head and neck mucosal premalignant recurrence and progression based on histology, treatment modality, and risk factors.
Design
Retrospective chart review.
Setting
Academic medical center.
Patients
Patients who were followed or treated for oral cavity dysplasia/carcinoma in situ.
Main outcomes measures
Comparisons with clinical features, degree of dysplasia, anatomical location, rate of recurrences as well as malignant transformation and overall outcome were made.
Results
Of the 136 patients who were included in the study, 20% (n=27) initially presented with mild dysplasia, 39% (n=53) with moderate dysplasia, 21% (n=29) with severe dysplasia, and 20% (n=27) with carcinoma in situ. Wide local excision (HR 0.54, p=0.05) was associated with reduced local recurrence in comparison to observation. In comparison to observation, both wide local excision (HR 0.43, p=0.04) and CO2/NO Yag laser treatment (HR 0.14, p=0.02) of dysplastic lesions significantly reduced progression to cancer. Management of mild dysplasia included observation (n=13), excision (n=10) and laser therapy (n=3). Six of the 13 observed patients suffered a premalignancy recurrence, whereas only 4 of the 13 patients who underwent excision/laser treatment experienced a recurrence. Similarly, 5/13 observed patients eventually progressed to malignancy in comparison to only 2/13 patients who underwent initial excision/laser treatment.
Conclusion
Wide excision and/or ablation of head and neck mucosal premalignancy is more effective than observation in preventing recurrence of premalignancy and progression to malignancy. Mild dysplasia has a potentially high rate of recurrence and progression to malignancy when observed, and may be treated by wide excision or ablation.
© 2013 Elsevier Ltd. All rights reserved.
Oral Oncology
Volume 49, Issue 8 , Pages 818-823, August 201315
P53 (Pro72Arg) polymorphism associated with the risk of oral squamous cell carcinoma in gutka, niswar and manpuri addicted patients of Pakistan
Saima Saleem
Abdul Hameed<a href="mailto:ahameed0786
Zubair Ahmed Abbasi<a href="mailto:drzubairahmedabbasi
Muhammad Ajmal<a href="mailto:ajmalpk1974
Received 19 July 2012; received in revised form 8 April 2013; accepted 14 April 2013. published online 16 May 2013.
Summary
Objectives
The chewing habit of paan, chhaliya, and tobacco is common in the traditional culture of Pakistan. Currently, niswar, gutka and manpuri are also commercially available in the Pakistani market. Epidemiologic evidences and increased rate of oral squamous cell carcinoma (OSCC) cases may indicate a direct relationship of these chewing habits with oral carcinogenesis. The p53 gene has been known to be a tumor suppressor gene that is found mutated in common human cancers. The p53 gene contains a single nucleotide polymorphism at codon 72 of exon 4 which encodes either proline (Pro) or arginine (Arg). The aim of the present study was to investigate association of p53 gene codon 72 polymorphism with patients of oral squamous cell carcinoma consuming these carcinogenic chewable materials.
Materials and Methods
Blood and tissue samples of 260 OSCC patients were collected with informed consent from the local hospitals of Karachi. The patients were compared with controls of similar age and sex. The exon 4 of p53 gene was examined by PCR-SSCP. The tumor samples showing mobility shift were purified and sequenced.
Results
The C>G missense mutation at nucleotide position 215 of the coding sequence was identified which substitutes proline with arginine at codon 72 of p53 protein. When the data for CCC72CGC polymorphism was analyzed statistically, a significant difference was observed between OSCC and control samples. The Pro allelic frequencies were significantly higher in OSCC patients as compare to controls. The current study indicated the Pro form of p53 codon 72 increases the risk of developing OSCC in Pakistani population. The risk ratio for Pro allele was 1.5004 (95% confidence interval: 1.2559 to 1.7924) and odds ratio of Pro allele was 2.389 (95% confidence interval: 1.5591 to 2.8137) in comparison with the Arg and Pro alleles in the OSCC group.
Conclusion
These evidences suggest that there may be specific genetic targets with these chewing ingredients that are responsible for causing OSCC. The p53 codon 72 polymorphism is associated with OSCC at somatic cell level but the polymorphism was not associated at inherited level.
© 2013 Elsevier Ltd. All rights reserved.
Oral Oncology
Volume 49, Issue 8 , Pages 824-829, August 201316
Adenoid cystic carcinoma of the head and neck: A single-center analysis of 105 consecutive cases over a 30-year period
Stijn van Weert
Elisabeth Bloemena
Isaäc van der Waal
Remco de Bree
Derek H.F. Rietveld
Joop D. Kuik
C. René Leemans
Received 23 January 2013; received in revised form 7 May 2013; accepted 9 May 2013. published online 10 June 2013.
Summary
Background
Adenoid cystic carcinoma is a rare salivary gland malignancy with a poor disease free survival due to frequent distant metastases and late local recurrences. Previous single-center reports on outcome mostly encompass small series. In this report a relative large series of 105 cases is analyzed, all treated at the VU University Medical Center, Amsterdam, The Netherlands over a 30-year period in which treatment strategies remained unchanged.
Methods
All cases of ACC of the head and neck between 1979 and 2009 at our institution were analyzed through a medical chart review. Recurrence patterns and possible prognostic factors (T-stage, N-status, age, gender, type of salivary gland involved, histological grade, surgical margins, perineural invasion (PNI) and postoperative radiotherapy (RT)) were analyzed.
Results
One-hundred and five cases of ACC of the head and neck were identified. Five-, ten- and twenty-year survival rates for overall survival were 68%, 52% and 28%, respectively. T-stage, N-status, surgical margins, histological subtype and age were highly significant predictors for survival. PNI was not a negative prognosticator.
Conclusions
T-stage, N-status, surgical margins, histological grade and age are the main predictors of survival-outcome in ACC of the head and neck. Distant metastasis frequently develop, mainly in the first 5years post treatment. Local recurrences often develop even later on, warranting long term follow up of patients treated for ACC. Grade III ACC should be considered a specific entity within the group of ACC due to its typical aggressive biological behavior and relatively poor outcome, implicating the need for an improved adjuvant treatment.
© 2013 Published by Elsevier Inc.
Oral Oncology
Volume 49, Issue 8 , Pages 830-834, August 201317
Multimodal treatment and long-term outcome of patients with esthesioneuroblastoma
A. Modesto
P. Blanchard
Y.G. Tao
M. Rives
F. Janot
E. Serrano
A. Benlyazid
J. Guigay
F.R. Ferrand
J.P. Delord
J. Bourhis
N. Daly-Schveitzer
Received 22 February 2013; received in revised form 29 April 2013; accepted 30 April 2013. published online 07 June 2013.
Summary
Purpose/objectives
To analyze the clinical features, treatment modalities and outcome of patients treated for a localized esthesioneuroblastoma (ENB).
Materials and methods
Forty-three consecutive patients with biopsy proven ENB treated at two referral cancer centers between 1998 and 2010 were retrospectively reviewed.
Results
Overall, 5 patients had stage A disease, 13 stage B, 16 stage C and 9 stage D according to the modified Kadish classification. Neo-adjuvant chemotherapy was performed in 23 patients leading to a 74 % response rate. Thirty-one patients were treated by surgery. Thirty-nine patients (90.6%) underwent radiation therapy. Twelve patients received bilateral cervical lymph node irradiation (LNI). After a median follow-up of 77months, the 5-year overall and progression free survival were 65% and 57%. Twelve patients (28%) had a locoregional relapse leading to 10 ENB-related deaths. The major prognostic factor was the modified Kadish stage with a 3-year survival for stage A–B, C and D of 100%, 48% and 22% respectively (p<0.0001). Two (9%) isolated cervical lymph node relapses occurred among staged B and C patients treated without elective LNI and none after elective or adjuvant LNI.
Conclusion
The high risk of locoregional failure in ENB justifies the use of multimodal therapy. Induction chemotherapy leads to a high response rate. Elective LNI might prevent regional failure in locally advanced disease.
© 2013 Elsevier Ltd. All rights reserved.
Oral Oncology
Volume 49, Issue 8 , Pages 835-841, August 201318
A randomized phase II study of docetaxel with or without vandetanib in recurrent or metastatic squamous cell carcinoma of head and neck (SCCHN)
Sewanti Limaye
Sarah Riley
Sihai Zhao
Anne O’Neill
Marshall Posner
Douglas Adkins
Zachary Jaffa
John Clark
Robert Haddad
Received 23 January 2013; received in revised form 24 April 2013; accepted 26 April 2013. published online 03 June 2013.
Summary
Objectives
There are limited chemotherapeutic options for advanced recurrent or metastatic SCCHN. The efficacy and toxicity of docetaxel with or without vandetanib was investigated in these patients.
Materials and Methods
Patients with pathologically confirmed, recurrent or metastatic SCCHN who had progressed on platinum based therapy given as definitive or palliative treatment, were randomized in this open label, multicenter phase II study of docetaxel (75mg/m2 IV Q3weeks) with or without vandetanib (100mg PO daily). The primary objective was response rate (RR) and secondary objectives were progression free survival (PFS), overall survival (OS), disease control rate (DCR) and duration of response (DOR).
Results
29 analyzable patients were enrolled, 14 in docetaxel arm and 15 in combined arm. PR was achieved in 1 patient in the docetaxel arm and 2 patients in the combined arm. The objective RR was 7% (1/14) (95% CI 0.2–33.8%) in the single and 13% (2/15) (95% CI 1.6–40.4%) combined arm. The median PFS was 3.21 (95% CI 3.0–22.0) and 9 (95% CI (5.86–18.1) weeks; median OS was 26.8(95% CI 17.7–100.7+) and 24.1 (95% CI, 16.4–171.1+) weeks. Most common adverse events were fatigue, dysphagia, diarrhea or constipation, cytopenias and alopecia.
Conclusions
Although an initial benefit in response was noted and statistical criteria met there was only a minor trend towards improved PFS for the combined arm. The study was designed with low threshold for activity in each arm and results were deemed not to be of enough clinical significance in this group of patients to continue accrual.
Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182,6932607174