Palliative head and neck radiotherapy with the RTOG 8502 regimen for incurable primary or metastatic cancers
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Oral Oncology
Highlights
- •We reviewed our experience with the RTOG 8502 regimen for incurable head and neck cancers.
- •Overall palliative response: 65%.
- •Grade 3 toxicity in 5% of patients, most commonly mucositis.
- •Greater number of RT cycles correlated with higher palliative response and survival.
Summary
Objectives
To report on our institutional experience of palliative radiotherapy (RT) of cancers in the head and neck by the RTOG 8502 'QUAD SHOT' regimen.
Methods
Seventy-five patients completed at least 1 cycle of palliative RT to the head and neck for primary or metastatic disease based on the RTOG 8502 regimen (3.7 Gy twice daily over 2 consecutive days at 4 week intervals per cycle) between 2/2005 and 7/2014.
Results
Median patient age was 76 years (range 23–97). The most common histologies were squamous cell carcinoma (55%), non-anaplastic thyroid carcinoma (10%) and salivary gland carcinoma (9%). Thirty patients (40%) received prior RT at the palliative site. Twenty-eight patients (37%) completed at least three RTOG 8502 cycles. Sixty-five percent of all patients had a palliative response. Median overall survival was 5.67 months (range, 0.20–34.5). Grade 3 toxicity in 4 patients (5%) consisted of acute dermatitis and functional mucositis. Palliative response was significantly correlated with increasing number of RTOG 8502 cycles (p = 0.012), but not KPS, prior RT, palliative chemotherapy, prior surgery, histology or stage. On survival analysis, palliative response (p < 0.001), KPS ⩾ 70 (p = 0.001), and greater number of RTOG 8502 cycles (p = 0.022) remained independent predictors of improved survival.
Conclusions
For patients with incurable malignant disease in the head and neck, the palliative RTOG 8502 'QUAD SHOT' regimen provides excellent rates of palliative response with minimal associated toxicity. Patients who are able to complete greater number of RT cycles have higher rates of palliative response and overall survival.
Assessing the relationship between oral chronic graft-versus-host disease and global measures of quality of life
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Oral Oncology
Highlights
- •cGVHD is associated with reduced QOL but oral cavity contributions remain unclear.
- •Isolated oral cGVHD is not associated with clinically significant better QOL.
- •Organ-specific cGVHD involvement can influence various QOL measures and outcomes.
Summary
Objective
Chronic GVHD (cGVHD) is a frequent complication of allogeneic hematopoietic stem cell transplantation (HSCT) and affects multiple organ systems, with the oral cavity being one of the most frequently affected sites. Patients with cGVHD experience reduced quality of life (QOL), yet the specific impact of oral cGVHD on QOL is poorly understood. The objective of this study was to characterize the impact of oral cGVHD on global measures of QOL.
Materials and methods
QOL data were collected using the FACT-BMT and SF-36 instruments for 569 patients enrolled in the Chronic GVHD Consortium, with a total of 1915 follow-up visits. At study enrollment, patients were categorized as isolated oral cGVHD (n = 22), oral and concomitant extra-oral cGVHD (n = 420), and only extra-oral cGVHD (n = 127). Utilizing all longitudinal data, QOL scores were compared using a multivariable linear model controlling for demographic, transplant, and cGVHD characteristics.
Results
Patients with isolated oral cGVHD reported better physical well-being (P = 0.009), BMT well-being (P = 0.01), and decreased bodily pain (P = 0.01) compared to patients with oral and concomitant extra-oral cGVHD, but the differences in scores did not reach the defined threshold for clinical significance (6 points for FACT-BMT domains and 5 points for SF-36 domains).
Conclusions
Global QOL scores are similar in patients with isolated oral cGVHD and patients with oral and concomitant extra-oral cGVHD.
Epstein-Barr virus infection is strictly associated with the metastatic spread of sinonasal squamous-cell carcinomas
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Oral Oncology
Highlights
- •Sinonasal squamous-cell carcinomas (SNSCC) are relatively rare, so the indication for elective neck dissection is difficult.
- •TP53 mutations were exclusively associated with shorter survival in SNSCC.
- •Other markers like EGFR, KRAS, PIK3CA, BRAF, p16 and HPV had no effect on the metastasis rate and survival.
- •Only the EBV positive tumors developed lymph node or distant metastases.
- •The presence of EBV is strictly associated with metastasis, so we recommend an elective neck dissection in patients with EBV-positive SNSCC.
Summary
Background
Sinonasal squamous-cell carcinomas (SNSCC) are relatively rare. Thus, data regarding the rate of lymph node metastases are inconsistent in contrast with well-known high metastasis rates in squamous-cell carcinomas of the head and neck (HNSCC) (oral cavity, pharynx and larynx). Hence, the indication for elective neck dissection is difficult in SNSCC. The aim of this study was to assess common genetic alterations and EBV and HPV status as a function of metastasis in SNSCC and HNSCC.
Methods
We retrospectively analyzed 44 SNSCC and 65 HNSCC for TP53, EGFR, KRAS, PIK3CA and BRAF mutations using a high-resolution melting analysis followed by Sanger sequencing. EBV and HPV detection was performed using in situ hybridization for virus encoded RNA. Tumor-associated p16INK4a expression was visualized by immunohistochemistry and correlated with HPV infection. The mutation data, EBV and HPV status were statistically compared with the clinical data in SNSCC and HNSCC.
Results
TP53 mutations were exclusively associated with shorter survival in SNSCC (p = 0.048). All the other markers had no effect on the metastasis rate and survival. In total, 20 of 44 SNSCC were EBV-positive. Only these EBV positive tumors developed lymph node or distant metastases (p = 0.008). LMP1 was positive in 14/44 patients. When combining both methods significance for a correlation between EBV/LMP1 positive patients and metastases was even higher (p = 0.001).
Conclusion
In SNSCC, the presence of EBV is strictly associated with metastasis. We recommend an elective neck dissection in patients with EBV-positive SNSCC.
Comparative study of sentinel lymph node biopsy in clinically N0 oral tongue squamous cell carcinoma: Long-term oncologic outcomes between validation and application phases
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Oral Oncology
Highlights
- •Compared oncologic outcomes between the validation and application phases of sentinel biopsy in tongue cancer patients.
- •False omission rate was higher in application phase than validation phase (11.7% vs 6.6%).
- •Stringent strategy of follow-up and salvage treatment is mandatory in the application phase.
- •By long-term observation, sentinel biopsy provides acceptable oncologic outcomes in tongue cancer patients during the transition from validation to application phase.
Summary
Objective
This study tested the long-term outcomes of sentinel lymph node biopsy (SLNB) for oral tongue squamous cell carcinoma (SCC) during the transition from validation to application phase.
Materials and methods
Sensitivity, negative predictive value (NPV), neck control rate, disease-specific survival (DSS), disease-free survival (DFS), and overall survival (OS) were compared in cN0 oral tongue SCC patients from different phases.
Results
A total of 133 SLNs from 61 patients (21 in the validation phase, 40 in the application phase) were harvested. Fourteen SLNs of 12 patients (6 in each phase) were positive for metastasis (occult metastasis rate, 19.6%). Regional recurrences developed from 5 negative SLNs (one in the validation phase, 4 in the application phase), of whom 3 patients were successfully salvaged. Sensitivity and NPV of the validation phase were both 100%, with 60.0% and 88.2% in the application phase. False omission rates were 6.6% (1/15) in the validation group, and 11.7% (4/34) in the application group, respectively. The neck control rate was 95.2% in the validation phase and 97.5% in the application phase (p = 0.52). No differences were evident in DSS, DFS, and OS between the two phases (DSS: 92.5% vs 95.2%, p = 0.69; DFS: 85.0% vs 90.4%, p = 0.40; OS: 90% vs 85.5%, p = 0.62). Subgroup analyses between negative- and positive-SLNs within each phase revealed no significant differences in all endpoints.
Conclusion
Given higher false negative cases in the application phase, stringent strategy of follow-up and salvage treatment is mandatory to maintain acceptable outcomes.
Narrow band imaging in the intra-operative definition of resection margins in oral cavity and oropharyngeal cancer
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Oral Oncology
Highlights
- •We propose a new surgical approach to reduce positive margins at histological examination.
- •We compare the resection margins defined with white light and narrow band imaging.
- •All margins were negative for dysplasia or cancer at extemporaneous histology.
- •One patient had a margin positive for cancer and one for moderate dysplasia at definitive histology.
- •25% of NBI-defined enlargements were positive for dysplasia and 75% for cancer.
Summary
Objectives
In oncological surgery, a three-dimensional resection 1.5–2 cm from the gross tumour edge is currently considered appropriate, and the status of resection margins is the most reliable indicator of radicality. Awareness of "field cancerization" calls for a re-evaluation of the benchmarks of tumour resection; however, its identification is not simple because the dysplastic areas may be far from the main lesion and difficult to recognize macroscopically. New technologies such as narrow band imaging (NBI) could improve the detection of neoplastic and pre-neoplastic areas, ensuring more precise resections. The main purpose of this study was to investigate the value of NBI in detecting pre-cancerous areas and/or cancer around the tumour bulk intra-operatively, to achieve adequate resection of the tumour.
Materials and Methods
The resection margins of 8 oral cavity and 8 oropharyngeal cancers were first drawn by macroscopic evaluation and then re-defined using NBI. Resections were performed following the NBI-drawing if extemporaneous histological examinations of the NBI-defined enlargements were positive for dysplasia or cancer. The number of clear margins was evaluated.
Results
Resections margins were free of tumour or dysplasia at extemporaneous examination; on definitive histology, two patients had a margin positive for cancer and dysplasia, respectively. Among the NBI-defined enlargements, 25% were positive for dysplasia and 75% for cancer. The sensitivity, specificity, positive and negative predictive values were 100%, 88.9%, 100% and 87.5%, respectively.
Conclusion
The method we propose could be useful for obtaining free surgical margins and reducing the potential development of tumour foci resulting from incomplete resection.
The epidemiology of head and neck squamous cell carcinoma in The Netherlands during the era of HPV-related oropharyngeal squamous cell carcinoma. Is there really evidence for a change?
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1Oral Oncology
Highlights
- •We evaluate trends in incidence of oral and oropharyngeal cancer.
- •The incidence of oropharyngeal cancer increases.
- •Among females, similar increases for oral tongue and cavity were found.
- •Smoking and alcohol consumption are the main cause for developing oral and oropharyngeal cancer.
- •Improved prognosis for oropharyngeal cancer is a result of a shift to concomitant chemoradiation therapy.
Summary
Background
Several recent studies have shown that incidence of oropharyngeal carcinomas is rising in the Western World. This increase has been attributed to changes in the etiology of oropharyngeal carcinomas with a growing role for infections with Human Papilloma viruses. This nationwide study evaluates and compares trends in incidence, clinical behavior and tumor characteristics of oropharyngeal and oral squamous cell cancer.
Methods
This study comprised all 16,480 patients with primary squamous cell carcinoma of the oral tongue (OTSCC), oral cavity excluding oral tongue (OCSCC), and oropharynx (OPSCC) diagnosed from 1989 through 2008 in The Netherlands. We assessed trends in age-standardized incidence, second cancer risk and subsite specific relative survival (RS) over time.
Results
Incidence of OTSCC and OPSCC in males and incidence of all subsites in females increased significantly from 1989 through 2008. In males increases in incidence were largely restricted to the 50–64 year age group (estimated annual percentage change 2.2% and 3.2% for OTSCC and OPSCC, respectively), while in females incidence increased for most age groups. The incidence of OCSCC (excl. oral tongue) and OPSCC before 50 years of age decreased. Patients with OPSCC showed the poorest prognosis with a relative survival of 41.6% after 5 years and 29.4% after 10 years (P < 0.001) over the entire period 1989–2008. However survival increased substantially for OPSCC patients over time (5-year RS of 37.2% in 1989–1993 to 47.6% in 2004–2008, P < 0.001).
Conclusion
Although incidence of OPSCC did increase since 1989, especially in females, similar increases were seen for OCSCC (excl. oral tongue) and OTSCC. Our study does not appear to support that HPV is the main contributor to a rising incidence of OPSCC as the effects of changes in smoking and alcohol use cannot be discounted.
Effect of taxanes-based induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma: A large scale propensity-matched study
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Oral Oncology
Highlights
- •Nasopharyngeal carcinoma got no benefit from taxanes-based induction chemotherapy.
- •But risk of distant metastasis lowered by 11.2% in cases of T4N1-2M0 and stage IVb.
- •It is better to target high risk patients and enroll enough cases in future trials.
Summary
Objectives
The effect of taxanes-based induction chemotherapy (IC) in locoregionally advanced nasopharyngeal carcinoma (LA-NPC) was quite contradictory in two phase II randomized controlled trials with small sample size. We aimed to investigate it in this large scale propensity-matched study.
Materials and methods
Totally, 779 LA-NPC patients who underwent intensity-modulated radiotherapy (IMRT) plus concurrent chemotherapy with or without taxanes-based IC were included. Patients in both treatment arms were matched using propensity score matching method at the ratio of 1:1. Failure-free survival (FFS), overall survival (OS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRFS) were assessed with Kaplan–Meier method, log-rank test and Cox regression analysis.
Results
After matching, 534 patients were identified for analysis. In univariate analysis, both treatment arms resulted in parallel survival (4-years FFS 78.0% vs 74.1%, P = 0.304; OS 87.5% vs 87.3%, P = 0.595; DMFS 88.2% vs 84.4%, P = 0.154; and LRFS 91.2% vs 90.1%, P = 0.960). In multivariate analysis, taxanes-based IC did not improve any survival (P ⩾ 0.139). And this association remained unchanged in subgroup analysis by age, sex and histology, and among patients with stage III and T4N0M0. But among patients with T4N1-2M0 and stage IVb, taxanes-based IC significantly prolonged the 4-year DMFS by 11.2% (86.1% vs 74.9%, P = 0.034), and marginally improved FFS (P = 0.133) and OS (P = 0.215) in both univariate and multivariate analysis.
Conclusions
In this large scale propensity-matched study, LA-NPC patients could not benefit from taxanes-based IC on the whole. But the risk of distant metastasis significantly decreased by above 10% for patients with T4N1-2M0 and stage IVb.
A systematic review of quality of life in head and neck cancer treated with surgery with or without adjuvant treatment
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Oral Oncology
Highlights
- •Systematic review with rigorous quality criteria.
- •Interrogates QoL data in HNC managed with surgery.
- •Limitations in design, reporting, interpretation and knowledge translation were found.
- •Reports symptom burden, temporal trends and predictive factors affecting QoL.
- •Advocates compliance to reporting guidelines to improve usability of QoL data.
Summary
Quality of life (QoL) is an important consideration in the management of head and neck cancers (HNC). We systematically reviewed the literature to assess the impact of curative surgical resection (+/− adjuvant therapy) of HNC on QoL. Eligible studies (participants > age 18 years, reported fully in English, and prospectively assessed QoL) were filtered using quality criteria, and classified according to the added value, using a published taxonomy. MEDLINE and EMBASE searching yielded 302 distinct reports, 49 met eligibility, and 26 met quality criteria.
Among the eligible studies, achievement of certain quality criteria was poor: a priori hypothesis (8%), statistical accounting of missing data (8%), reporting of assessment interval (35%) and rationale for chosen measure (53%). The most frequent ways QoL added value were: understanding of treatment benefit and risk (100%), comparing treatments for QoL effect (92%) and advancing QoL research methodology (50%). QoL (physical/social functioning and various symptom domains) deteriorated with treatment, gradually recovering to baseline (cancer diagnosis) level. Swallowing, chewing, saliva, taste, eating disruption, and aesthetic deficits may persist. Advanced tumors, extensive surgical resection, need for flap reconstruction, neck dissection, and postoperative radiation are associated with worse QoL outcomes.
Knowledge of these trends can be applied in shared decision making, identification of commonly faced QoL issues, and to develop and provide survivorship resources. Future research should focus on routinely incorporating QoL in randomized studies, reporting the result according to guidelines, and following knowledge translation principles to maximize the clinician's and patient's ability to use QoL data.
The management of oral epithelial dysplasia: The Liverpool algorithm
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Oral Oncology
Moesin regulates the motility of oral cancer cells via MT1-MMP and E-cadherin/p120-catenin adhesion complex
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Oral Oncology
Highlights
- •Cytoplasmic expression of Moesin indicated poor prognosis of OSCCs.
- •Moesin-silencing suppressed the motility of OSCC cells.
- •Moesin regulated the motility of OSCC cells via MT1-MMP and E-cadherin/p120-catenin adhesion complex.
Summary
Objective
The present study aimed to clarify the role of Moesin in oral squamous cell carcinoma (OSCC) progression, especially in regulation of cell motility.
Materials and Methods
Immunohistochemistry and western blotting were used to investigate the expression of Moesin, E-cadherin, p120-catenin and MT1-MMP in normal epithelia, dysplasia and OSCCs. Then, Moesin was knockdown by siRNA in OSCC cell lines, WSU-HN6 and CAL27, and the biological role of Moesin in cell adhesion and motility was evaluated by transwell system, cell spreading and aggregation assays. The interactions between Moesin, MT1-MMP and E-cadherin/p120-catenin complex were determined by co-immunoprecipitation and immunofluorescence.
Results
Moesin expression was found decreased in the membrane and increased in cytoplasm during the malignant transformation of oral epithelia, and cytoplasmic overexpression of Moesin correlated with nodal metastasis and poor prognosis of OSCCs. Furthermore, Moesin-silencing induced an increased cell–cell adhesion but decreased invasiveness, which was subsequently demonstrated might due to Moesin-mediated E-cadherin and p120-catenin interaction. Meantime, Moesin-silencing significantly down-regulated MT1-MMP expression, accompanied by reduced cell motility and impaired filopodia formation, which was also observed when MT1-MMP knockdown by RNAi or tissue inhibitor (TIMP2), indicating the involvement of MT1-MMP in Moesin-mediated cell motility. Finally, the relationship between Moesin, E-cadherin and MT1-MMP was confirmed in OSCC tissue samples.
Conclusion
Taken together, our results indicate Moesin may regulate cell motility through its interactions with MT1-MMP and E-cadherin/p120-catenin adhesion complex and cytoplasmic expression of Moesin correlates with nodal metastasis and poor prognosis of OSCCs, indicating Moesin may be a potential candidate for targeted gene therapy for OSCCs.
Corrigendum to "Significance of nuclear p-mTOR expression in advanced oral squamous cell carcinoma with extracapsular extension of lymph node metastases" [Oral Oncol. 51(5) (2015) 493–499]
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Oral Oncology
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