Quality of life following treatment with intra-arterial cisplatin with concurrent radiation and erlotinib for locally advanced head and neck cancer.

OBJECTIVES: Studies that focus on the feasibility of using erlotinib plus chemoradiation to treat locally advanced head and neck cancer have given hints of improved survival outcomes compared to chemoradiation alone. However, the influence of this treatment regimen on the quality of life of the patients has not been documented. We conducted a study of this triple combination and now have documented follow-up survival data as well as long-term quality of life (QoL) measures. METHODS: Three sets of QoL questionnaires were given to patients with a diagnosis of head and neck cancer at two time points, pre- and post-treatment, to assess differences in quality of life after receiving chemotherapy with intra-arterial (IA) cisplatin (150 mg/m2), concomitant radiation (70 Gy), and oral erlotinib (150 mg/day). Additionally, patients were followed for a total of 5 years. RESULTS: Treatment had a detrimental effect on appearance, taste, and saliva domain scores in their QoL questionnaires. Nonetheless, fewer patients reported pain and anxiety. SIGNIFICANCE OF RESULTS: The combination of erlotinib with chemoradiation produced similar adverse effects on the QoL scores of patients with head and neck cancer as compared to chemoradiation alone.

Standardization for oncologic head and neck surgery.

The inherent variability in performing specific surgical procedures for head and neck cancer remains a barrier for accurately assessing treatment outcomes, particularly in clinical trials. While non-surgical modalities for cancer therapeutics have evolved to become far more uniform, there remains the challenge to standardize surgery. The purpose of this review is to identify the barriers in achieving uniformity and to highlight efforts by surgical groups to standardize selected operations and nomenclature. While further improvements in standardization will remain a challenge, we must encourage surgical groups to focus on strategies that provide such a level.

Management of the Neck in Well-Differentiated Thyroid Cancer.

PURPOSE OF REVIEW: In this narrative review, we discuss the indications for elective and therapeutic neck dissections and the postoperative surveillance and treatment options for recurrent nodal disease in patients with well-differentiated thyroid cancer. RECENT FINDINGS: Increased availability of advanced imaging modalities has led to an increased detection rate of previously occult nodal disease in thyroid cancer. Nodal metastases are more common in young patients, large primary tumors, specific genotypes, and certain histological types. While clinically evident nodal disease in the lateral neck compartments has a significant oncological impact, particularly in the older age group, microscopic metastases to the central or the lateral neck in well-differentiated thyroid cancer do not significantly affect outcome. As patients with clinically evident nodal disease are associated with worse outcomes, they should be treated surgically in order to reduce rates of regional recurrence and improve survival. The benefit of elective neck dissection remains unverified as the impact of microscopic disease on outcomes is not significant.

The role of adjuvant treatment in early-stage oral cavity squamous cell carcinoma: An international collaborative study.

BACKGROUND: Up to half of patients with oral cavity squamous cell carcinoma (OCSCC) have stage I to II disease. When adequate resection is attained, no further treatment is needed; however, re-resection or radiotherapy may be indicated for patients with positive or close margins. This multicenter study evaluated the outcomes and role of adjuvant treatment in patients with stage I to II OCSCC. METHODS: Overall survival (OS), disease-specific survival, local-free survival, and disease-free survival rates were calculated with Kaplan-Meier analysis. RESULTS: Of 1257 patients with T1-2N0M0 disease, 33 (2.6%) had positive margins, and 205 (16.3%) had close margins. The 5-year OS rate was 80% for patients with clear margins, 52% for patients with close margins, and 63% for patients with positive margins (P < .0001). In a multivariate analysis, age, depth of invasion, and margins were independent predictors of outcome. Close margins were associated with a >2-fold increase in the risk of recurrence (P < .0001). The multivariate analysis revealed that adjuvant treatment significantly improved the outcomes of patients with close/positive margins (P = .002 to .03). CONCLUSIONS: Patients with stage I to II OCSCC and positive/close margins have poor long-term outcomes. For this population, adjuvant treatment may be associated with improved survival. Cancer 2018;124:2948-55. © 2018 American Cancer Society.

Intra-arterial chemoradiotherapy for head and neck cancer.

Intra-arterial chemotherapy has been used to treat localized malignant neoplasms in patients with head and neck cancer for over 50 years as the head and neck region is particularly well suited to regional chemotherapy. Early intra-arterial chemotherapy did not prove its efficacy. In addition, the additional complications associated with establishing and maintaining arterial access have further dampened enthusiasm for this approach. Subsequent significant advances in vascular radiology techniques and the development of new devices, such as fluoroscopy units and angiographic catheters, have made possible safe, accurate and repeated superselective intra-arterial chemotherapy. Intra-arterial infusion of high-dose cisplatin with systemic neutralization by intravenous sodium thiosulfate (RADPLAT) is a theoretically attractive approach to the treatment of advanced head and neck cancer. However, a Dutch trial comparing intra-arterial and intravenous chemoradiotherapy for advanced head and neck cancer showed that RADPLAT was not superior to intravenous chemoradiotherapy. Therefore, further investigation of RADPLAT, including the refinement of the indications for its application, is needed.

Treatment Selection for T3/T4a Laryngeal Cancer: Chemoradiation Versus Primary Surgery.

OBJECTIVE: We report the treatment outcomes, including organ preservation, for patients with locally advanced (T3/T4a) laryngeal cancer receiving both surgical and nonsurgical approaches. We hypothesize that selection of treatment protocols aimed to optimize organ preservation does not compromise survival provided careful selection is done through the process of multidisciplinary treatment planning. METHODS: Patients with T3-4a laryngeal squamous cell cancer were evaluated and recommended for primary treatment with total or partial laryngectomy (37 patients) or chemoradiotherapy (34 patients). Treatment outcomes were compared between the 2 cohorts. In addition, the laryngeal preservation rate and laryngoesophageal dysfunction-free survival (LEDFS) were determined for the chemoradiation group. RESULTS: The 5-year overall survival rate for patients with T3 lesions was 41% and 40% for the surgical and nonsurgical groups, respectively, and for T4 lesions it was 54% and 53%, respectively. For the chemoradiation group, the rate of overall laryngeal preservation was 79%. LEDFS at 2 years was 40% for T3 lesions and 33% for T4 lesions. CONCLUSION: Through careful selection, some patients with locally advanced laryngeal cancer can be offered chemoradiation (organ preservation) without compromising survival. However, the patients selected to receive chemoradiation have a high rate of laryngeal and esophageal dysfunction.

Impact of prophylactic central neck dissection on oncologic outcomes of papillary thyroid carcinoma: a review.

Prophylactic neck dissection (PND) for papillary thyroid carcinoma (PTC) is controversial. Our aim was to assess current levels of evidence (LE) according to the Oxford Centre for Evidence-based Medicine ( http://www.cebm.net/?O=1025 ) regarding the oncologic benefits of PND. Data were analyzed via MEDLINE keywords: PTC, differentiated thyroid carcinoma, PND, central lymph node metastases, central compartment, recurrence-free survival. There was conflicting evidence regarding the rate of reoperation for recurrence, with some studies showing a lower rate after PND with increased recurrence-free survival and a higher rate of undetectable pre- and post-ablation thyroglobulin levels (LE 4), whereas other studies did not show a difference (LE 4). Only one study (LE 4) showed improved disease-specific survival with PND. PND may improve recurrence-free survival, although this is supported by only a low LE. Current recommendations can only be based on low-level evidence.

Refining Measurement of Social Cognitive Theory Factors Associated with Exercise Adherence in Head and Neck Cancer Patients.

Social cognitive theory (SCT) measures related to exercise adherence in head and neck cancer (HNCa) patients were developed. Enrolling 101 HNCa patients, psychometric properties and associations with exercise behavior were examined for barriers self-efficacy, perceived barriers interference, outcome expectations, enjoyment, and goal setting. Cronbach's alpha ranged from.84 to.95; only enjoyment demonstrated limited test-retest reliability. Subscales for barriers self-efficacy (motivational, physical health) and barriers interference (motivational, physical health, time, environment) were identified. Multiple SCT constructs were cross-sectional correlates and prospective predictors of exercise behavior. These measures can improve the application of the SCT to exercise adherence in HNCa patients.

The prognosis of N2b and N2c lymph node disease in oral squamous cell carcinoma is determined by the number of metastatic lymph nodes rather than laterality: evidence to support a revision of the American Joint Committee on Cancer staging system.

BACKGROUND: A study was conducted to assess for prognostic heterogeneity within the N2b and N2c classifications for oral cancer based on the number of metastatic lymph nodes and to determine whether laterality of neck disease provides additional prognostic information. METHODS: An international multicenter study of 3704 patients with oral cancer undergoing surgery with curative intent was performed. The endpoints of interest were disease-specific survival and overall survival. Model fit was assessed by the Akaike Information Criterion and comparison of models with and without the covariate of interest using a likelihood ratio test. RESULTS: The median number of metastatic lymph nodes was significantly higher in patients with N2c disease compared to those with N2b disease (P < .001). In multivariable analyses stratified by study center, the addition of the number of metastatic lymph nodes improved model fit beyond existing N classification. Next, the authors confirmed significant heterogeneity in prognosis based on the number of metastatic lymph nodes (≤ 2, 3-4, and ≥ 5) in patients with both N2b and N2c disease (P < .001). A proposed reclassification combining N2b and N2c disease based on the number of metastatic lymph nodes demonstrated significant improvement in prognostic accuracy compared with the American Joint Committee on Cancer staging system, and no improvement was noted with the addition of a covariate for contralateral or bilateral neck disease (P = .472). CONCLUSIONS: The prognosis of patients with oral cancer with N2b and N2c disease appears to be similar after adequate adjustment for the burden of lymph node metastases, irrespective of laterality. Based on this finding, the authors propose a modified lymph node staging system that requires external validation before implementation in clinical practice.

The controversy in the management of the N0 neck for squamous cell carcinoma of the maxillary sinus.

Squamous cell carcinoma (SCC) of the maxillary sinus is a relatively rare disease. As the reported incidence of regional metastasis varies widely, controversy exists as to whether or not the N0 classified neck should be treated electively. In this review, the data from published series are analyzed to decide on a recommendation of elective treatment of the neck in maxillary SCC. The published series consist of heterogeneous populations of different subsites of the paranasal sinuses, different histological types, different staging and treatment modalities used and different ways of reporting the results. These factors do not allow for recommendations based on high levels of evidence. Given this fact, the relatively high incidence rate of regional metastasis at presentation or in follow-up in the untreated N0 neck, and the relatively low toxicity of elective neck irradiation, such irradiation in SCC of the maxillary sinus should be considered.

Treatment of the neck in residual/recurrent disease after chemoradiotherapy for advanced primary laryngeal cancer.

Concomitant chemoradiotherapy (CRT) is extensively used as primary organ preservation treatment for selected advanced laryngeal squamous cell carcinomas (LSCC). The oncologic outcomes of such regimens are comparable to those of total laryngectomy followed by adjuvant radiotherapy. However, the management of loco-regional recurrences after CRT remains a challenge, with salvage total laryngectomy being the only curative option. Furthermore, the decision whether to perform an elective neck dissection (END) in patients with rN0 necks, and the extent of the neck dissection in patients with rN + necks is still, a matter of debate. For rN0 patients, meta-analyses have reported occult metastasis rates ranging from 0 to 31 %, but no survival advantage for END. In addition, meta-analyses also showed a higher incidence of complications in patients who received an END. Therefore, END is not routinely recommended in addition to salvage laryngectomy. Although some evidence suggests a potential role of END for supraglottic and locally advanced cases, the decision to perform END should weigh benefits against potential complications. In rN + patients, several studies suggested that selective neck dissection (SND) is oncologically safe for patients with specific conditions: when lymph node metastases are not fixed and are absent at level IV or V. Super-selective neck dissection (SSND) may be an option when nodes are confined to one level. In conclusion, current evidence suggests that in rN0 necks routine END is not necessary and that in rN + necks with limited nodal recurrences SND or a SSND could be sufficient.

Superselective neck dissection: rationale, indications, and results.

It has been established that an appropriately indicated selective neck dissection can achieve the same oncologic results as more extensive dissections. An even more modified selective neck dissection, termed superselective neck dissection, involves the compartmental removal of the fibrofatty tissue contents within the defined boundaries of two or fewer contiguous neck levels. Evidence from retrospective studies suggests that superselective neck dissection (SSND) is oncologically sound for two indications: elective treatment of the clinically N0 neck and salvage treatment of persistent lymph node disease after chemoradiotherapy. While there is broader support for the former scenario, evidence that SSND may constitute optimal treatment in the latter is in conformity with the trend toward developing surgical techniques that provide better functional outcomes without compromising efficacy.

The evolving role of selective neck dissection for head and neck squamous cell carcinoma.

Neck dissection is an important part of the surgical treatment of head and neck squamous cell carcinoma (HNSCC). The historical concept of neck dissection implied the removal of all lymph node-bearing tissue in the neck, which began in the late nineteenth century. However, more conservative variations of neck dissection have been performed and promoted as well. Anatomic, pathologic, clinical investigations, and prospective studies have demonstrated that the lymphatic dissemination of HNSCC occurs in predictable patterns. Supported by these studies, selective neck dissection (SND), which consists of the removal of select levels of lymph nodes in the neck that have the highest risk of harboring undetected metastases, has become widely accepted in the treatment of the clinically uninvolved neck. More recently, evidence supports using SND in a therapeutic setting in selected cases of HNSCC with limited metastatic disease. Additionally, even more targeted dissections referred to as super-selective neck dissection have been explored for selected patients undergoing elective node dissection for supraglottic cancer and as an adjuvant therapy for salvage of residual lymphadenopathy confined to a single neck level following chemoradiation. In the future, the trend to tailor treatment to individual patients and to limit toxicity and morbidity may further increase the use of SND. The indications have to be guided by further research, in relation with non-surgical treatment options while optimizing oncological effectiveness.

Emerging Concepts Impacting Head and Neck Cancer Surgery Morbidity.

All treatment modalities for head and neck cancer carry with them a risk of adverse events. Head and neck surgeons are faced with significant challenges to minimize associated morbidity and manage its sequelae. Recognizing situations in which a surgical complication is an adverse event inherent to the procedure can alleviate the psychologic impact a complication might have on the treatment team and minimize external and internal pressures. Focusing on the complications that can be effectively modified, future complications can be avoided. Also, some surgical morbidities may not be preventable, necessitating the option to reconsider whether the incidents should be labeled toxic reactions rather than a complication. This discussion highlights some of the areas in which additional research is needed to achieve the goal of minimizing the impact of surgical morbidity.

Pharyngeal Reconstruction Methods to Reduce the Risk of Pharyngocutaneous Fistula After Primary Total Laryngectomy: A Scoping Review.

INTRODUCTION: The most common early postoperative complication after total laryngectomy (TL) is pharyngocutaneous fistula (PCF). Rates of PCF are higher in patients who undergo salvage TL compared with primary TL. Published meta-analyses include heterogeneous studies making the conclusions difficult to interpret. The objectives of this scoping review were to explore the reconstructive techniques potentially available for primary TL and to clarify which could be the best technique for each clinical scenario. METHODS: A list of available reconstructive techniques for primary TL was built and the potential comparisons between techniques were identified. A PubMed literature search was performed from inception to August 2022. Only case-control, comparative cohort, or randomized controlled trial (RCT) studies were included. RESULTS: A meta-analysis of seven original studies showed a PCF risk difference (RD) of 14% (95% CI 8-20%) favoring stapler closure over manual suture. In a meta-analysis of 12 studies, we could not find statistically significant differences in PCF risk between primary vertical suture and T-shaped suture. Evidence for other pharyngeal closure alternatives is scarce. CONCLUSION: We could not identify differences in the rate of PCF between continuous and T-shape suture configuration. Stapler closure seems to be followed by a lower rate of PCF than manual suture in those patients that are good candidates for this technique.

Recurrent Differentiated Thyroid Cancer: The Current Treatment Options.

Differentiated thyroid carcinomas (DTC) have an excellent prognosis, but this is sometimes overshadowed by tumor recurrences following initial treatment (approximately 15% of cases during follow-up), due to unrecognized disease extent at initial diagnosis or a more aggressive tumor biology, which are the usual risk factors. The possible sites of recurrence are local, regional, or distant. Local and regional recurrences can usually be successfully managed with surgery and radioiodine therapy, as are some isolated distant recurrences, such as bone metastases. If these treatments are not possible, other therapeutic options such as external beam radiation therapy or systemic treatments should be considered. Major advances in systemic treatments have led to improved progression-free survival in patients previously considered for palliative treatments; among these treatments, the most promising results have been achieved with tyrosine kinase inhibitors (TKI). This review attempts to give a comprehensive overview of the current treatment options suited for recurrences and the new treatments that are available in cases where salvage surgery is not possible or in cases resistant to radioiodine.

Artificial Intelligence in Head and Neck Cancer: A Systematic Review of Systematic Reviews.

INTRODUCTION: Several studies have emphasized the potential of artificial intelligence (AI) and its subfields, such as machine learning (ML), as emerging and feasible approaches to optimize patient care in oncology. As a result, clinicians and decision-makers are faced with a plethora of reviews regarding the state of the art of applications of AI for head and neck cancer (HNC) management. This article provides an analysis of systematic reviews on the current status, and of the limitations of the application of AI/ML as adjunctive decision-making tools in HNC management. METHODS: Electronic databases (PubMed, Medline via Ovid, Scopus, and Web of Science) were searched from inception until November 30, 2022. The study selection, searching and screening processes, inclusion, and exclusion criteria followed the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. A risk of bias assessment was conducted using a tailored and modified version of the Assessment of Systematic Review (AMSTAR-2) tool and quality assessment using the Risk of Bias in Systematic Reviews (ROBIS) guidelines. RESULTS: Of the 137 search hits retrieved, 17 fulfilled the inclusion criteria. This analysis of systematic reviews revealed that the application of AI/ML as a decision aid in HNC management can be thematized as follows: (1) detection of precancerous and cancerous lesions within histopathologic slides; (2) prediction of the histopathologic nature of a given lesion from various sources of medical imaging; (3) prognostication; (4) extraction of pathological findings from imaging; and (5) different applications in radiation oncology. In addition, the challenges in implementation of AI/ML models for clinical evaluations include the lack of standardized methodological guidelines for the collection of clinical images, development of these models, reporting of their performance, external validation procedures, and regulatory frameworks. CONCLUSION: At present, there is a paucity of evidence to suggest the adoption of these models in clinical practice due to the aforementioned limitations. Therefore, this manuscript highlights the need for development of standardized guidelines to facilitate the adoption and implementation of these models in the daily clinical practice. In addition, adequately powered, prospective, randomized controlled trials are urgently needed to further assess the potential of AI/ML models in real-world clinical settings for the management of HNC.

Review of Outcomes after Salvage Surgery for Recurrent Squamous Cell Carcinoma of the Head and Neck.

Surgery with adjuvant chemoradiotherapy or chemoradiotherapy is the mainstay in treatment for advanced stage head and neck squamous cell carcinoma; however, locoregional recurrences are frequent. Salvage surgery could be proposed in selected patients to improve local control, disease-free, and overall survival. Factors for improved disease-free and overall survival in patients treated with salvage surgery include age, tumor location, the initial T stage, HPV status, resection margins, and the time elapsing from the initial treatment. Clinical trials with adjuvant therapies have shown promise after salvage surgery in terms of tolerance and response, but clinical guidelines for using these adjuvant treatments are currently lacking. The aim of this review is to present current knowledge concerning the incidence and management of recurrent head and neck squamous cell carcinoma and current data concerning survival and morbidity after salvage surgery.

Lymph Node Metastases from Non-Melanoma Skin Cancer of the Head and Neck.

Non-melanoma skin cancer (NMSC) represents the most common malignancy in the world, comprising exceedingly common lesions such as basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) and rare lesions such as Merkel cell carcinoma. Risk factors are widely recognized and include ultraviolet (UV) light exposure, radiation exposure, immunosuppression, and many others. As a whole, survival and functional outcomes are favorable, but each histopathological subtype of NMSC behaves differently. Treatment regimens for the primary site usually include wide surgical excision and neck dissection in cases of clinically involved metastatic lymph nodes. The elective management of draining nodal basins, however, is a contested topic. Nearly all subtypes, excluding BCC, have a significant risk of lymphatic metastases, and have been studied with regard to sentinel lymph node biopsy (SLNB) and elective neck dissection. To date, no studies have definitively established a true single standard of care, as exists for melanoma, for any of the NMSCs. As a result, the authors have sought to summarize the current literature and identify indications and management options for the management of the cervical lymphatics for each major subtype of NMSC. Further research remains critically necessary in order to develop complete treatment algorithms.

Survival Outcomes in T3 Laryngeal Cancers: Primary Total Laryngectomy vs. Concurrent Chemoradiation or Radiation Therapy-A Meta-Analysis.

BACKGROUND: The management of cT3 laryngeal cancers remains controversial, with studies recommending surgical or non-surgical approaches. Despite the many papers that have been published on the subject, there is a lack of studies showing which treatment has better results in terms of survival. OBJECTIVE: To determine the difference in survival outcomes following total laryngectomy (TL), concurrent chemoradiation (CRT) or radiation therapy (RT) alone in T3 laryngeal cancers. METHODS: Search of PubMed, Scopus, and Google Scholar databases from 1995 to 2023 employing specific keywords and Boolean operators to retrieve relevant articles. Statistical analysis was conducted using a random-effects model, and heterogeneity was evaluated using the Q-test and I2 statistic. Funnel plot asymmetry was assessed using rank correlation and regression tests. RESULTS: The qualitative data synthesis comprised 10,940 patients from 16 included studies. TL was performed in 2149 (19.4%), CRT in 6723 (61.5%), RT in 295 (2.7%), while non-surgical treatment was not specified in 1773 (16.2%) patients. The pooled 2-year overall survival (OS) rates were TL = 73%, CRT = 74.7%, RT = 57.9%, 3-year OS rates were TL = 64.3%, CRT = 62.9%, RT = 52.4%, and 5-year OS rates were TL = 54.2%, CRT = 52.7%, RT = 40.8%. There was a significant heterogeneity in the included studies. There was no statistically significant difference in 2-year OS (logOR= -0.88 (95% confidence interval (CI): -1.99 to 0.23), p = 0.12), 3-year OS (logOR = -0.6 (95% CI: -1.34 to 0.15), p = 0.11), and 5-year OS (logOR = -0.54 (95% CI: -1.29 to 0.21), p = 0.16) between TL and CRT. Instead, there was significant difference in 2-year OS (logOR= -1.2383 (95% CI: -2.1679 to -0.3087), p = 0.009), 3-year OS (-1.1262 (95% CI: -1.6166 to -0.6358), p < 0.001), and 5-year OS (-0.99 (95% CI: -1.44 to -0.53)), p < 0.001) between TL and RT alone. CONCLUSIONS AND SIGNIFICANCE: TL followed with adjuvant (chemo)radiation on indication and CRT with salvage surgery in reserve appear to have similar OS outcomes. Both resulted in better OS outcomes compared to RT alone in the treatment of T3 laryngeal cancers. If patients are unfit for chemotherapy, making CRT impossible, surgery may become the choice of treatment.