Cancers of the head & neck最新文献

Abstract: Treatment modalities of head and neck squamous cell cancer include surgery, radiation, chemotherapy, targeted agents and immune checkpoint inhibition. Treatment is often toxic and can affect long-term function and quality of life. In this context, identification of biomarker data that can help tailor therapy on an individualized basis and reduce treatment-related toxicity would be highly beneficial. A variety of predictive biomarkers have been discovered and are already utilized in clinical practice, while many more are being explored. We will review p16 overexpression as a surrogate biomarker in HPV-associated head and neck cancer and plasma EBV DNA as a biomarker in nasopharyngeal carcinoma, the two established biomarkers currently utilized in clinical practice. We will also examine novel predictive biomarkers that are in clinical development and may shape the future landscape of targeted head and neck cancer therapy. These emerging biomarkers include the tyrosine kinases and their signaling pathway, immune checkpoint biomarkers, tumor suppressor abnormalities, and molecular predictors of hypoxia-targeted therapy. We will also look at futuristic biomarkers including detection of circulating DNA from clinical specimens and rapid tumor profiling. We will highlight the ongoing effort that will see a shift from prognostic to predictive biomarker development in head and neck cancer with the goal of delivering individualized cancer therapy.

Trial registration: N/A.

Background: Transoral endoscopic head and neck surgery (eHNS), including transoral laser microsurgery (TLM) and transoral robotic surgery (TORS), provides access to subsites in the head and neck that have traditionally been difficult to approach. Minor salivary gland tumors, while relatively uncommon, are frequently malignant and can occur at sites in the oropharynx accessible by transoral eHNS. Presented here is the largest review to date of patients with minor salivary gland tumors of the oropharynx managed with transoral eHNS as primary or salvage therapy.

Methods: A retrospective chart review was performed, including data from 20 patients with minor salivary gland tumors of the oropharynx managed with transoral eHNS at 2 tertiary, academic medical centers. Details of tumor pathology, margin analysis, adjuvant therapy, and an assessment of oncologic outcome were included.

Results: The base of tongue was the most common tumor site (75%). Adenoid cystic carcinoma (ACC) accounted for most cases (35%), and negative margins were obtained in most (95%) through an endoscopic-only approach. Overall, 50% of patients received post-operative radiation therapy. Postoperative complications were limited, with one patient (5%) returning to the OR for control of post-operative oropharyngeal bleeding. On average follow-up of 36 months, 90% of patients were alive with no evidence of recurrence.

Conclusion: In this experience, transoral eHNS provided a safe and consistent surgical approach to management of minor salivary gland malignancies, with low complication rates and good locoregional control. Thus, transoral eHNS may play a valuable role in the multi-disciplinary management of these malignancies.

Trial registration number: None/not applicable.

Background: To find out how chemotherapy given prior to concurrent chemoradiotherapy compares with concurrent chemoradiation alone in the treatment of locally advanced nasopharyngeal cancer.

Methods: Patient charts were examined and found to have submitted to one of two regimes as follows: Neoadjuvant chemotherapy consisting of Cisplatin and 5-fluorouracil followed by concurrent chemoradiotherapy with cisplatin (group1), or concurrent cisplatin based chemoradiotherapy only (group 2). Radiation treatment dose of 70Gy in 35 fractions was given in each group.

Results: Forty-seven patients were evaluated with 68% male. Stage 4 disease comprised 83%, WHO type 3 was the commonest histologic type (53.2%). Median follow up period was 20 months (4-129). The 3-year overall survival for group 1 was 52.1%, and for group 2:65.7% (p = 0.47). The 3-year disease free survival for group 1 was 61.4, and 81.4% for group 2 (p = 0.03).

Conclusion: The study revealed that concurrent chemoradiation alone yields better disease free survival compared to chemotherapy given prior to it. There is however no difference in overall survival between the two regimes.

Background: Small cell carcinoma (SCC) is a rare variant of head and neck cancer characterized by a high-grade neuroendocrine cancer with similar features to small cell lung carcinoma (SCLC). Human papillomavirus (HPV) is an increasingly recognized cause of head and neck cancer but usually associated squamous cell carcinoma of the oropharynx. In this report, we present the clinical presentation, diagnosis, and management of a patient with HPV-related SCC of the oropharynx that responded favorably to chemotherapy with cisplatin plus etoposide and concomitant radiation therapy, a regimen typically used in SCLC.

Case presentation: We present a rare case of a 56-year-old man who presented with a three-month history of an enlarging left-sided neck mass. Imaging was consistent with a soft tissue density at the left tongue base, left level IIB nodal conglomerate, and multiple bilateral cervical lymph nodes, without evidence of distant metastasis. The patient underwent a core biopsy of the left neck level II node which read as a poorly differentiated neuroendocrine carcinoma consistent with small cell carcinoma. Polymerase chain reaction revealed that the tumor was positive for HPV16. The tumor was staged T1N2cM0 (stage IVA). He went on to receive four cycles of cisplatin and etoposide. On cycle two, he started radiotherapy to the oropharynx and involved neck nodes. He received a dose of 70 Gray (2 Gy/fraction) over a seven week-period. During the concomitant phase of chemo-radiation, the patient experienced grade IV mucositis, grade II nausea, and dehydration for which he received additional outpatient fluid and electrolyte replacement. Three months after completion of therapy, a PET/CT showed complete resolution of the tumor and metastatic lymph nodes along with no evidence of distant metastasis.

Conclusion: Patients with HPV-related cancer of the oropharynx require identification of the small cell variant to optimize therapy and improve outcomes.

Locally advanced (stage III or IV) squamous cell carcinoma of the head and neck (SCCHN) often requires multimodal treatment, consisting of a combination of surgery, radiation, and/or systemic therapy, namely chemotherapy or targeted agents. The expression of the epidermal growth factor receptor (EGFR) has been detected in more than 90% of all cases of SCCHN and has been correlated with decreased survival rates, resistance to radiotherapy, loco-regional treatment failure, and increased rates of distant metastases. This paper discusses several strategies aimed at targeting EGFR in combination with radiation. Until now, cetuximab, an anti-EGFR monoclonal antibody, is the only targeted agent that has been shown to improve overall survival in combination with radiation therapy. However, considering that there are multiple mechanisms of primary and acquired resistance to EGFR inhibitors, we focused on dissecting molecular pathways of EGFR inhibition to find alternative or complementary strategies for increasing tumour responsiveness. We suggest that the combination of treatments targeting the EGFR pathway and drugs aimed at increasing immune responses represent a promising approach that deserves to be further explored.

Thyroid cancer incidence is rapidly increasing due to increased detection and diagnosis of indolent thyroid cancer, i.e. cancer that is likely to be clinically insignificant. Clinical, radiologic, and pathologic features predicting indolent behavior of thyroid cancer are still largely unknown and unstudied. Existing clinicopathologic staging systems are useful for providing prognosis in the context of treated thyroid cancer but are not designed for and are inadequate for predicting indolent behavior. Ultrasound studies have primarily focused on discrimination between malignant and benign nodules; some studies show promising data on using sonographic features for predicting indolence but are still in their early stages. Similarly, molecular studies are being developed to better characterize thyroid cancer and improve the yield of fine needle aspiration biopsy, but definite markers of indolent thyroid cancer have yet to be identified. Nonetheless, active surveillance has been introduced as an alternative to surgery in the case of indolent thyroid microcarcinoma, and protocols for safe surveillance are in development. As increased detection of thyroid cancer is all but inevitable, increased research on predicting indolent behavior is needed to avoid an epidemic of overtreatment.

Background: The present study evaluated clinical outcomes for patients with head and neck squamous cell carcinoma presenting with N3 nodal disease.

Methods: A retrospective analysis of N3 head and neck squamous cell carcinoma patients was performed. Pearson chi-square and Wilcoxon signed-rank tests were used to analyze patient demographics, disease characteristics, and treatment variables. Survival was evaluated using Kaplan-Meier curves with the log-rank test. Univariate analysis using Cox proportional hazards models was used to define factors associated with overall survival. Patient and tumor characteristics associated with treatment assignments were analyzed by univariate multinomial logistic regression.

Results: We identified 36 patients with radiographically-defined N3 disease. For the entire cohort, median follow-up was 23.6 (range 2.8-135.0) months, and overall survival was 60% at 2 years and 30% at 5 years. Overall survival was similar between patients receiving primary surgery, radiotherapy, or chemoradiotherapy (p = 0.10). Primary, regional, and distant control at 5 years was 71%, 66%, and 53%, respectively. There was a trend towards improved regional control with primary surgery (p = 0.07). Planned neck dissection following primary chemoradiotherapy did not improve regional control (p = 0.55). Patients with p16-positive tumors exhibited improved overall (p = 0.05) and metastatic recurrence-free survival (p < 0.05). There were no factors predictive of treatment assignment nor factors associated with overall survival, local and regional control, or distant metastases free-survival on univariate analysis.

Conclusions: Patients with N3 head and neck squamous cell carcinoma exhibit 5-year overall survival rates of approximately 30% regardless of treatment modality. Planned neck dissection does not improve regional control in patients undergoing definitive chemoradiotherapy. p16-positive patients represent a favorable cohort. Distant failure comprises the major failure pattern and should be the focus of future studies in improving the outcome of this patient cohort.

Current adjuvant treatment guidelines for oropharyngeal squamous cell carcinoma treated with primary surgery are based on studies that predate the human papillomavirus (HPV) era. HPV-associated oropharynx carcinoma (HPV-OPC) has a much more favorable prognosis compared to HPV-unassociated cancer and is increasingly considered to be a distinct disease entity due to its unique etiology, presentation, and behavior. Currently, there is significant interest in adjuvant treatment de-intensification of HPV-OPC patients in order to reduce treatment-related toxicity while maintaining excellent clinical outcomes. Here, we review the evidence and rationale underlying the ongoing prospective trials of adjuvant treatment de-intensification for HPV-OPC patients.

Background: Oropharyngeal cancer is frequently associated with human papilloma virus, that also represents a strong prognostic factor. Local relaps and treatment-related complications are frequent, whereas distant metastases occur in about 25% of patients.

Case presentation: A 49 years-old male presented with a loco-regionally advanced oropharyngeal squamous cell carcinoma and was treated with concomitant chemoradiation. A complete clinical and pathological response was achieved, but the occurrence of necrotising tracheo-esophagitis, with tracheo-mediastino-pleural fistula formation, further complicated the subsequent clinical course. The patient died suddenly. Autopsy revealed multiple myocardial and epicardial metastases from oropharyngeal squamous cell carcinoma.

Conclusions: Even in case of a transient complete local response, the potential occurrence of severe complications and distant metastases, although infrequent, should be considered. Cardiac metastases are frequently underestimated, as they are often asymptomatic, but may lead to sudden death. Further efforts are needed to improve diagnosis and therapy in this setting.

For complex reconstruction of osseous defects of the head and neck, three-dimensional (3D) computer planning has been available for over 20 years. However, despite its availability and recent refinements, it is a technology that has not been widely adopted. While 3D computer planning has been proposed to improve surgical precision, reduce operating time and enhance functional outcomes, the objective evidence supporting these claims is limited. Here we review the recent literature that supports the use of 3D computer planning for complex osseous defects of the mandible. We highlight a case example where 3D modeling played a critical role, particularly during the virtual surgical planning stage. Finally, we propose that routine post-operative 3D analysis become an essential element in determining operative success. Critical evaluation of outcomes will better define its use in complex reconstruction of osseous defects.