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The aim of this study was to assess the validity of a treatment strategy for T1N0 glottic squamous cell carcinoma. One hundred and seventeen patients were prospectively treated according to institutional guidelines. using 1) laser microsurgery (L) for exophytic tumor, limited to one vocal cord, without extension to the anterior commissure or the vocal process of the arytenoid cartilage, 2) radiotherapy (RT) for large or infiltrative tumor reaching the anterior commissure or the vocal process of the arytenoid cartilage, poor endoscopic exposure and cT1b or 3) partial laryngectomy (PL) for tumor infiltrating the anterior commissure. Ninety-five patients were treated with RT and 22 with surgery alone (S) [L:19; PL:3]. The 5-year overall survival (OS) and disease-specific survival (DSS) were 81.5% and 97.1% (median follow-up: 73 months), respectively. There was no statistically significant difference in OS or DSS between patients treated with RT or S (logrank test: p = 0.974 and 0.978). The 5-year ultimate local control rate reached 98.3%. The local control rate with larynx preservation was 94.9% with no difference between RT (94.7%) and S (95.5%) (χ2: p = 0.891). Continued smoking after RT was significantly associated with a lower 5-year OS (77.9% versus 87%), [HR 3.458; p = 0.043 (95%CI 1.010–11.837)]. For patients with T1 glottic carcinoma, and based on our previous studies, these data prospectively confirm the oncologic validity of an institutional treatment strategy. Continued smoking after RT correlated with poor OS. [ABSTRACT FROM AUTHOR]

Background: Human papillomavirus (HPV) prevalence in oropharynx squamous cell carcinoma (OPSCC) is on the rise. HPV-linked OPSCCs represent a distinct clinical entity with a better treatment response and patient survival compared to tumors not linked to HPV. An emerging role in treatment response has been attributed to immune cell infiltration in human tumors. In this study, we investigated immune cell infiltration in human SCC of the head and neck region and its relation to overall survival after treatment with surgery (with or without radiotherapy) or concomitant chemo (or cetuximab)- radiotherapy. Materials and methods: Paraffin-embedded tumor samples of 136 patients with SCC of the larynx, hypopharynx, oral cavity and oropharynx were processed for immunohistochemical detection of CD3+ T-cells, CD8+ cytotoxic T-cells, CD20+ B-cells and CD163+ M2 macrophages within the tumor infiltrated area. Clinico-pathological data were analyzed as a function of tumor location and p16-status. Immune cell infiltration was represented as stained area on the whole tumor infiltrated area, compared for the different tumor locations and correlated to patient survival. Results: Patients with oropharynx tumors expressing significant p16 levels (p16-sg) had a 5-year overall survival of 85% compared to 43% for patients with no significant p16 (p16-ns) expression (HR: 0.3 - 95% CI: 0.1-0.6). Median immune cell infiltration (T- and B-lymphocytes) was significantly elevated in p16-sg oropharyngeal tumors, compared to p16-ns oropharyngeal tumors and to all other head and neck tumor locations. No difference in CD163+ macrophage infiltration was observed across the different patient groups. In the whole population, a high infiltration by CD3+ T-lymphocytes was associated to a significantly (p=.03; HR: 0.6, 95% CI: 0.4-0.97) better overall survival. Conclusion: Oropharynx cancer with significant p16 expression showed an increased overall survival and elevated T- and B-lymphocyte infiltration, which suggests a prognostic relevance of immune cell infiltration. [ABSTRACT FROM AUTHOR]

Adequate treatment of lymph node metastases is essential for patients with head and neck squamous cell carcinoma (HNSCC). However, there is still no consensus on the optimal surgical treatment of the neck for patients with a clinically positive (cN+) neck. In this review, we analyzed current literature about the feasibility of selective neck dissection (SND) in surgically treated HNSCC patients with cN + neck using the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. From the reviewed literature, it seems that SND is a valid option in patients with cN1 and selected cN2 neck disease (non-fixed nodes, absence of palpable metastases at level IV or V, or large volume ->3 cm-multiple lymph nodes at multiple levels). Adjuvant (chemo) radiotherapy is fundamental to achieve good control rates in pN2 cases. The use of SND instead a comprehensive neck dissection (CND) could result in reduced morbidity and better functional results. We conclude that SND could replace a CND without compromising oncologic efficacy in cN1 and cN2 cases with the above-mentioned characteristics. [ABSTRACT FROM AUTHOR]

Objective: Salvage surgery in recurrent SCCHN is associated with poor outcomes. This study aimed to better identify suitable surgical candidates and those at high risk of new recurrence.Materials and Methods: Single-center retrospective analysis of 109 patients undergoing salvage surgery for recurrent SCCHN. Univariate and multivariate analyses were used to identify prognostic factors affecting disease-free survival (DFS).Results: The following factors showed a significant impact on DFS: Disease-free interval >6months [HR 0.53; p=0.04], age>70years [HR 0.26; p=0.03], primary chemoradiotherapy [HR 2.39; p<0.01] compared to radiotherapy, oropharynx [HR 5.46; p<0.01] and hypopharynx [HR 3.92; p=<0.01] sites, compared to larynx, initial stage III [HR 7.10; p<0.01] and stage IV [HR 4.13; p<0.01], compared to stage I, locoregional recurrence [HR 4.57; p<0.01], compared to local recurrence. Univariate analysis also identified significant postoperative predictors of poor DFS including flap reconstruction [HR 3.44; p<0.01], postoperative complications [HR 2.09; p=0.01], positive margins [HR 3.64; p<0.01] and close margins [HR 3.83; p<0.01]. On multivariate analysis, oropharynx site [HR 3.98; p<0.01], initial stage III [HR 5.93; p<0.01] and locoregional recurrence [HR 2.93; p=0.04] were independent preoperative prognostic factors for DFS. Positive margins [HR 2.32; p=0.04], close margins [HR 2.94; p=0.02], extracapsular spread (ECS) [HR 4.04; p=0.03] and postoperative complications [HR 3.64; p<0.01] were independent postoperative prognostic factors.Conclusions: Patients with advanced primary nonlaryngeal tumor and locoregional recurrence have limited success with salvage surgery. Because patients with positive margins and ECS are at high risk of relapse, adjuvant treatment should be discussed. [ABSTRACT FROM AUTHOR]

Regional metastasis is a prominent feature of head and neck squamous cell carcinoma (HNSCC) and is an important prognostic factor. The currently available imaging techniques for assessment of the neck have limitations in accuracy; thus, elective neck dissection has remained the usual choice of management of the clinically N0 neck (cN0) for tumors with significant (≥20%) incidence of occult regional metastasis. As a consequence, the majority of patients without regional metastasis will undergo unnecessary treatment. The purpose of this review was to discuss new developments in techniques that potentially improve the accuracy of the assessment of the neck in patients with HNSCC. Although imaging has improved in the last decades, a limitation common to all imaging techniques is a lack of sensitivity for small tumor deposits. Therefore, complementary to improvements in imaging techniques, developments in more invasive diagnostic procedures, such as sentinel node biopsy (SNB) will add to the accuracy of diagnostic algorithms for the staging of the neck. [ABSTRACT FROM AUTHOR]

Neck dissection is an important treatment for metastases from upper aerodigestive carcinoma; an event that markedly reduces survival. Since its inception, the philosophy of the procedure has undergone significant change from one of radicalism to the current conservative approach. Furthermore, nonsurgical modalities have been introduced, and, in many situations, have supplanted neck surgery. The refinements of imaging the neck based on the concept of neck level involvement has encouraged new philosophies to evolve that seem to benefit patient outcomes particularly as this relates to diminished morbidity. The purpose of this review was to highlight the new paradigms for surgical removal of neck metastases using an evidence-based approach. © 2014 Wiley Periodicals, Inc. Head Neck 37: 915-926, 2015 [ABSTRACT FROM AUTHOR]

Among patients with head and neck squamous cell carcinoma with a negative neck who are initially treated with (chemo)radiotherapy, a number of cases will recur locally without obvious neck recurrence. There is little information available as to the most efficacious management of the neck in these cases. We have reviewed the literature to see what conclusions can be drawn from previous reports. We conducted a bibliography search on MEDLINE and EMBASE databases. Studies published in the English language and those on squamous cell carcinoma of the oral cavity, nasopharynx, oropharynx, larynx and hypopharynx were included. Data related to neck management were extracted from the articles. Twelve studies satisfied the inclusion criteria. Five studies reported only one treatment plan (either neck dissection or observation), while the others compared neck dissection to observation. The rate of occult metastases ranged from 3.4 to 12 %. The studies included a variable distribution of primary sites and stages of the recurrent primary tumors. The risk of occult neck node metastasis in a clinically rN0 patient correlated with tumor site and T stage. Observation of the neck can be suggested for patients with T1-2 glottic tumors, who recurred with less advanced tumors (rT1-2). For patients with more advanced laryngeal recurrences or recurrence at other high-risk sites, neck dissection could be considered for the rN0 patient, particularly if the neck was not included in the previous radiation fields. [ABSTRACT FROM AUTHOR]

Abstract: Despite progress in the therapeutic management of patients with squamous cell carcinoma of the head and neck (SCCHN), the mortality rate of patients presenting with advanced disease remains high. One approach to improve treatment efficacy is to add novel molecular targeted agents to the classical treatment regimens. Monoclonal antibodies targeting the epidermal growth factor receptor (EGFR) have shown clinical benefits in palliative and curative settings. However, only a minority of patients presenting with recurrent or metastatic (R/M) SCCHN have meaningful tumor regression with these agents and virtually all who do develop acquired tumor resistance after a few months of treatment. For these reasons, other inhibitors of EGFR or molecules that interfere with known molecular pathways activated in SCCHN are of considerable interest, either as single agents or in combination with other treatment modalities. In this review, we discuss the different molecular therapeutic approaches explored in SCCHN. We also briefly outline new trial designs that could be used to accelerate the investigation of emerging therapeutic agents in this disease. [Copyright &y& Elsevier]

Post-therapy follow-up for patients with head and neck cancer other than upper aerodigestive tract squamous cell carcinoma should meet several objectives: to detect both local, regional or distant recurrences, to evaluate acute and long-term treatment-related side effects, to guide the rehabilitation process, and to provide psychosocial support when needed. To our knowledge, there are no published reports in the literature dedicated to the follow-up of patients with these tumours. A comprehensive literature search for post-treatment follow-up strategies spanning from 1980 to 2012 was performed on several databases. This review focuses on malignant salivary gland tumors, soft tissue sarcomas, cutaneous squamous cell carcinomas, and sinonasal adenocarcinomas. Given the varying biological behavior and treatment-related factors and based on the literature, different recommendations are made on the follow-up of patients with the above-mentioned tumors. [ABSTRACT FROM AUTHOR]

The management of head and neck squamous cell carcinomas does not end with the completion of ablative therapy. The oncologic objectives of post-treatment follow-up are to detect recurrences and second primary tumors; beyond that, follow-up should evaluate acute and chronic treatment-related side effects, guide the rehabilitation process, alleviate functional loss, manage pain, restore nutritional status and assess psychosocial factors. In this structured review, we address the questions of timing and the tools required to achieve a complete and coherent routine surveillance. Several guidelines and consensus statements recommend clinical examination as the cornerstone of follow-up which should be performed for at least 5 years, although there are no data in favor of any one particular follow-up program, and only low-level evidence suggests an improvement in oncologic outcomes by close follow-up. Baseline imaging (computed tomography and magnetic resonance imaging) should be obtained within 2-6 months after definitive therapy if used for treatment response evaluation. Metabolic response, if indicated, should be assessed preferably after 3 months in patients who undergo curative-intent therapy with (chemo)-radiotherapy. Chest computed tomography is more sensitive than plain radiography, if used in follow-up, but the benefit and cost-effectiveness of routine chest computed tomography has not been demonstrated. There are no current data supporting modifications specific to the surveillance plan of patients with human papillomavirus-associated disease. [ABSTRACT FROM AUTHOR]

The authors reflects on the continued use of the radical neck dissection (RND) in treating patients with head and neck squamous cell carcinoma (HNSCC). They explain the process of the RND, which removes all the lymphatic and non-lymphatic structures of the mandible and clavicle. They reveal that the procedure has not been widely use in the medical community until the advances of antibiotics, blood transfusion, and modern anesthesia allow safe and efficacious operation.

Background The purpose of this study was to investigate the value of p53 functional analysis of separated alleles in yeast (FASAY) as a witness of p53/p21 pathway alteration in head and neck squamous cell carcinoma (HNSCC). Methods The p53 transcriptional activity was prospectively analyzed in 82 newly diagnosed patients with HNSCC. FASAY and p53 immunostaining were carried out on paired tumoral and histologically normal tissues. The predictive value of FASAY for locoregional recurrence was assessed by Cox survival analysis. Results Loss of p53/p21 transcriptional activity was encountered in 88% tumoral and 18% histologically normal samples, associated with mutations (79%) and insertions/deletions (21%). The p53 overexpression underestimated p53 transcriptional abnormalities. FASAY-positive histologically normal mucosa was significantly associated with locoregional recurrence. Conclusion FASAY positivity indicates field cancerization in a subgroup of patients with HNSCC, in which nonfunctional p53 was significantly associated with locoregional recurrence. This prompted us to pursue the study on the p53 functional status of normal mucosa in patients with HNSCC. © 2011 Wiley Periodicals, Inc. Head Neck, 2011 [ABSTRACT FROM AUTHOR]

Summary: Concurrent chemotherapy and radiotherapy (CRT) has become standard treatment for many patients with advanced head and neck squamous cell carcinoma (HNSCC). This has led to controversy concerning the role of neck dissection (ND) in this setting. The current debate is focused on N2–N3 disease and the ability of a clinical complete response to predict the absence of viable cells in the ND specimen. Proponents of a systematic planned ND argue that it improves regional control and possibly disease-specific survival. They assert that a clinical response does not predict the pathologic response, and that in the event of recurrence in the neck, a surgical salvage procedure is unlikely to succeed. Conversely, there are many arguments in favor of performing ND only for patients who have evidence of residual neck disease because of the very low probability of isolated neck recurrence following a complete response. Proponents argue that for complete responders, planned ND is associated with no survival benefit. As planned surgery will only benefit patients with residual disease in the neck alone, there is a high rate of unnecessary ND with its associated morbidity. Another question concerns the appropriate type of ND to be performed. Even if required after chemoradiation, selective ND is oncologically feasible with minimal morbidity. Lastly, robust data from a randomized trial demonstrating the superiority of one approach vs. the other are lacking. After conducting a review of recent literature on the subject, the authors conclude that planned ND is not necessary for patients with complete response because of the availability of improved diagnostic follow up modalities, and the increased sensitivity to CRT of HNSCC, particularly HPV associated tumors. [Copyright &y& Elsevier]

Abstract: Background and purpose: To assess the efficacy and safety of gefitinib given concomitantly and/or as maintenance therapy to standard cisplatin/radiotherapy for previously untreated, unresected, stage III/IV non-metastatic SCCHN. Materials and methods: In this phase II, double-blind, study, 226 patients were randomized to gefitinib 250mg/day, 500mg/day or placebo in two phases: a concomitant phase (gefitinib or placebo with chemoradiotherapy), followed by a maintenance phase (gefitinib or placebo alone). Primary endpoint was local disease control rate (LDCR) at 2years; secondary endpoints were LDCR at 1year, objective response rate, progression-free survival, overall survival, and safety and tolerability. Results: Gefitinib (250 and 500mg/day) did not improve 2-year LDCR compared with placebo either when given concomitantly with chemoradiotherapy (32.7% vs. 33.6%, respectively; OR 0.921, 95% CI 0.508, 1.670 [1-sided p =0.607]) or as maintenance therapy (28.8% vs. 37.4%, respectively; OR 0.684, 95% CI 0.377, 1.241 [1-sided p =0.894]). Secondary efficacy outcomes were broadly consistent with the 2-year LDCR results. In both doses, gefitinib was well-tolerated and did not adversely affect the safety and tolerability of concomitant chemoradiotherapy. Conclusion: Gefitinib was well-tolerated, but did not improve efficacy compared with placebo when given concomitantly with chemoradiotherapy, or as maintenance therapy alone. [Copyright &y& Elsevier]

For patients with advanced regional disease, neck dissection following (chemo)radiotherapy remains controversial. Selective neck dissection (SND) was reported as suitable after chemoradiation in patients with advanced regional disease. Reduced morbidity represents the major advantage of SND. In a situation in which there is a major fibrosis around the previously invaded nodes, resection of 1 or more nonlymphatic structures may be required. The current classification of SND could be implemented by the addition of extended selective neck dissection (ESND). The standard basic procedures for SND spare the sternocleidomastoid muscle (SCM), the internal jugular vein (IJV), and the spinal accessory nerve (SAN). When an SND is associated with the resection of 1 or more nonlymphatic structures, it should be termed ESND. All additional nonlymphatic structure(s) removed should be identified in parentheses. The proposal to subclassify SND not only in accord with the resected lymph node levels but also upon the nonlymphatic structures removed may be of some help to avoid potential misinterpretation. © 2010 Wiley Periodicals, Inc. Head Neck, 2010 [ABSTRACT FROM AUTHOR]

Background: This study compared automated vs. manual tissue grinding in terms of RNA yield obtained from oral mucosa biopsies. Methods: A total of 20 patients undergoing uvulectomy for sleep-related disorders and 10 patients undergoing biopsy for head and neck squamous cell carcinoma were enrolled in the study. Samples were collected, snap-frozen in liquid nitrogen, and divided into two parts of similar weight. Sample grinding was performed on one sample from each pair, either manually or using an automated cell disruptor. The performance and efficacy of each homogenization approach was compared in terms of total RNA yield (spectrophotometry, fluorometry), mRNA quantity [densitometry of specific TP53 amplicons and TP53 quantitative reverse-transcribed real-time PCR (qRT-PCR)], and mRNA quality (functional analysis of separated alleles in yeast). Results: Although spectrophotometry and fluorometry results were comparable for both homogenization methods, TP53 expression values obtained by amplicon densitometry and qRT-PCR were significantly and consistently better after automated homogenization (p<0.005) for both uvula and tumor samples. Functional analysis of separated alleles in yeast results was better with the automated technique for tumor samples. Conclusions: Automated tissue homogenization appears to be a versatile, quick, and reliable method of cell disruption and is especially useful in the case of small malignant samples, which show unreliable results when processed by manual homogenization. Clin Chem Lab Med 2009;47:294–301. [ABSTRACT FROM AUTHOR]

Combined small cell carcinoma (SMCC) of the larynx consists of SMCC admixed with a component of squamous cell carcinoma or adenocarcinoma. These tumors are very rare and, to date, only a few cases have been fully described. This points out the lack of information available about the correct management of these patients. Here, we describe two additional cases of combined SMCC of the larynx that illustrate the difficulties that we can encounter to diagnose correctly these patients and, by consequence, to treat them adequately. [ABSTRACT FROM AUTHOR]

Background. We assessed the prevalence of histologically proven normal or invaded lymph nodes in the apex of level V. Methods. Seventy neck dissections were performed in 41 patients with mucosal head and neck squamous cell carcinoma (SCC). Fifty-one neck dissections were performed in 30 previously untreated patients (group 1); 19 neck dissections were carried out in 11 patients previously irradiated (group 2). Results. Pathologic analysis was unable to identify any lymph node in 70% of the apex specimens. In group 1, no lymph nodes were detected in 63%, whereas one or more noninvaded lymph nodes were present in 37%; in group 2, no lymph nodes were identified in 89%, whereas one or more normal lymph nodes were found in 11% (p = .03). Metastatic lymph nodes were never identified. Conclusions. The prevalence of lymph nodes in the apex was 30%. No invaded lymph nodes were identified. In addition to anatomic evidence, these results suggest that dissection of the apex is not necessary in mucosal head and neck SCC. © 2005 Wiley Periodicals, Inc. Head Neck27: XXX–XXX, 2005 [ABSTRACT FROM AUTHOR]

Background: Larynx cancer is a common site for tumors of the upper aerodigestive tract. In cases with a clinically negative neck, the indications for an elective neck treatment are still debated. The objective is to define the prevalence of occult metastasis based on the subsite of the primary tumor, T classification and neck node levels involved. Methods: All studies included provided the rate of occult metastases in cN0 larynx squamous cell carcinoma patients. The main outcome was the incidence of occult metastasis. The pooled incidence was calculated with random effects analysis. Results: 36 studies with 3803 patients fulfilled the criteria. The incidence of lymph node metastases for supraglottic and glottic tumors was 19.9% (95% CI 16.4–23.4) and 8.0% (95% CI 2.7–13.3), respectively. The incidence of occult metastasis for level I, level IV and level V was 2.4% (95% CI 0–6.1%), 2.0% (95% CI 0.9–3.1) and 0.4% (95% CI 0–1.0%), respectively. For all tumors, the incidence for sublevel IIB was 0.5% (95% CI 0–1.3). Conclusions: The incidence of occult lymph node metastasis is higher in supraglottic and T3–4 tumors. Level I and V and sublevel IIB should not be routinely included in the elective neck treatment of cN0 laryngeal cancer and, in addition, level IV should not be routinely included in cases of supraglottic tumors. [ABSTRACT FROM AUTHOR]

Chemoradiotherapy has emerged as a gold standard in advanced squamous cell carcinoma of the head and neck (SCCHN). Because 50% of advanced stage patients relapse after nonsurgical primary treatment, the role of salvage surgery (SS) is critical because surgery is generally regarded as the best treatment option in patients with recurrent resectable SCCHN. Surgeons are increasingly confronted with considering operation among patients with significant effects of failed non-surgical primary treatment. Wide local excision to achieve clear margins must be balanced with the morbidity of the procedure, the functional consequences of organ mutilation, and the likelihood of success. Accurate selection of patients suitable for surgery is a major issue. It is essential to establish objective criteria based on functional and oncologic outcomes to select the best candidates for SS. The authors propose first to understand preoperative prognostic factors influencing survival. Predictive modeling based on preoperative information is now available to better select patients having a good chance to be successfully treated with surgery. Patients with a high comorbidity index, advanced oropharyngeal or hypopharyngeal primary tumors, and both local and regional recurrence have a very limited likelihood of success with salvage surgery and should be strongly considered for other treatments. Following SS, identifying patients with postoperative prognostic factors predicting high risk of recurrence is essential because those patients could benefit of adjuvant treatment or be included in clinical trials. Finally, defining HPV tumor status is needed in future studies including recurrent oropharyngeal SCC patients. [ABSTRACT FROM AUTHOR]

Abstract: Background: The simultaneous integrated boost (SIB) technique with dose per fraction slightly higher than 2Gy offers the advantages of shortening the treatment time and increasing the biologically equivalent dose to the tumor. This study was designed to evaluate the feasibility of a dose-escalating radiotherapy treatment by using a SIB-IMRT approach in patients with early and moderately advanced head and neck cancers. Materials and methods: Fifty-seven consecutive patients with pharyngo-laryngeal T2N0 or T2N1, or laryngeal T3N0 SCC were included. The therapeutic PTVs were treated according to three consecutive dose levels i.e., 69Gy in 30 fractions of 2.3Gy (dose level I), 72Gy in 30 fractions of 2.4Gy (dose level II) or 75Gy in 30 fractions of 2.5Gy (dose level III). The prophylactic PTVs received a dose of 55.5Gy delivered in 30 fractions of 1.85Gy. The primary endpoint of the study was acute toxicity assessed during treatment and during the first 3months following the completion of radiotherapy. The secondary endpoints included loco-regional control, disease-free survival, overall survival and late toxicity at 2years of follow-up. The study design allowed patients to be enrolled in the second dose level group if no more than 10% of grade 4 acute toxicity was observed on the first dose level group within 3months after the completion of IMRT, and so on for the third level group. Results: Forty-four men and 13 women were included in the trial. The majority of them presented with oropharyngeal cancer (53%) and laryngeal cancer (33%). Only 3 patients developed grade 4 acute mucositis during treatment, one in each dose level. Thirty-two patients (56%) experienced grade 3 toxicity, mostly dermatitis and mucositis, without any significant difference between the groups. Late grade 1 and 2 xerostomia was seen in 53% and 33% of patients, respectively. Transient grade 4 late toxicity was observed in 16% of all patients and was equally distributed among the groups. The 2-year loco-regional control was 82% for all 3 groups (79% dose level I, 88% dose level II, 79% dose level III). The 2-year overall survival was 89% for dose level I and II, and 95% for dose level III. Conclusions: This dose escalation SIB-IMRT protocol was safe and effective as the sole treatment of early and moderately advanced SCC of head and neck. No toxicity difference was observed between the groups. [Copyright &y& Elsevier]

The study investigated the association between hospital volume and observed survival of patients with a head and neck squamous cell carcinoma (HNSCC). Overall, 9245 patients diagnosed with HNSCC between 2009 and 2014, were identified in the population-based Belgian Cancer Registry. This database was coupled with other databases providing information on diagnostic and therapeutic procedures, vital status, and comorbidities. The overall and relative survival probabilities were estimated using the Kaplan-Meier and the Ederer II methods, respectively. The relation between hospital volume and observed survival since diagnosis was then assessed using Cox proportional hazard models adjusted for potential confounders. The care for patients with HNSCC in Belgium was dispersed over more than 99 centres with half of the centres treating four or less patients with HNSCC per year. Survival probabilities were significantly better for patients treated in higher volume centres (>20 patients/year): the median survival of patients treated in these centres was 1.1 year longer (5.1 versus 4.0 years) than in lower volume centres. This association was confirmed in analyses taking the case-mix between hospitals into account: the hazard to die of any cause decreased on average with 0.4% per increase of one additionally treated patient. Beyond 20 assigned patients per year, there was no further decrease in the hazard to die. Statistically significant and clinically relevant improved survival probabilities were obtained in patients treated in higher volume centres (>20 patients/year) compared with their peers treated in lower volume centres. This supports the recommendation to concentrate the care for patients with HNSCC in reference centres. • Half of the Belgian hospitals treated four or less eligible HNSCC patients per year. • Survival was significantly better for patients treated in higher volume centres. • The care for patients with HNSCC should be concentrated in reference centres. [ABSTRACT FROM AUTHOR]

In 1994 a decision analysis, based on the literature and utility ratings for outcome by a panel of experienced head and neck physicians, was presented which showed a threshold probability of occult metastases of 20% to recommend elective treatment of the neck. It was stated that recommendations for the management of the cN0 neck are not immutable and should be reconfigured to determine the optimal management based on different sets of underlying assumptions. Although much has changed and is published in the almost 25 years after its publication, up to date this figure is still mentioned in the context of decisions on treatment of the clinically negative (cN0) neck. Therefore, we critically reviewed the developments in diagnostics and therapy and modeling approaches in the context of decisions on treatment of the cN0 neck. However, the results of studies on treatment of the cN0 neck cannot be translated to other settings due to significant differences in relevant variables such as population, culture, diagnostic work-up, follow-up, costs, institutional preferences and other factors. Moreover, patients may have personal preferences and may weigh oncologic outcomes versus morbidity and quality of life differently. Therefore, instead of trying to establish "the" best strategy for the cN0 neck or "the" optimal cut-off point for elective neck treatment, the approach to optimize the management of the cN0 neck would be to develop and implement models and decision support systems that can serve to optimize choices depending on individual, institutional, population and other relevant variables. [ABSTRACT FROM AUTHOR]

Abstract Purpose Few studies have reported large inter-observer variations in target volume selection and delineation in patients treated with radiotherapy for head and neck squamous cell carcinoma. Consensus guidelines have been published for the neck nodes (see Grégoire et al., 2003, 2014), but such recommendations are lacking for primary tumour delineation. For the latter, two main schools of thoughts are prevailing, one based on geometric expansion of the Gross Tumour Volume (GTV) as promoted by DAHANCA, and the other one based on anatomical expansion of the GTV using compartmentalization of head and neck anatomy. Method For each anatomic location within the larynx, hypopharynx, oropharynx and oral cavity, and for each T-stage, the DAHANCA proposal has been comprehensively reviewed and edited to include anatomic knowledge into the geometric Clinical Target Volume (CTV) delineation concept. A first proposal was put forward by the leading authors of this publication (VG and CG) and discussed with opinion leaders in head and neck radiation oncology from Europe, Asia, Australia/New Zealand, North America and South America to reach a worldwide consensus. Results This consensus proposes two CTVs for the primary tumour, the so called CTV-P1 and CVT-P2, corresponding to a high and lower tumour burden, and which should be associated with a high and a lower dose prescription, respectively. Conclusion Implementation of these guidelines in the daily practice of radiation oncology should contribute to reduce treatment variations from clinicians to clinicians, facilitate the conduct of multi-institutional clinical trials, and contribute to improved care of patients with head and neck carcinoma. [ABSTRACT FROM AUTHOR]

Purpose: The presence of positive nodes in the neck is an important prognostic factor in oral squamous cell carcinoma. The aim of this study was to determine the optimal cut-off value of tumor thickness (TT) and a clinically relevant risk of positive nodes in patients cN0. Material and methods: We retrospectively reviewed 108 cT1-2N0 oral tongue and floor of the mouth squamous cell carcinoma who had primary surgery between 1994 and 2012. Results: Mean age was 57,7years (23–95). The male:female ratio was 2.7:1. Oral tongue was involved in 64 (59.3 %) patients, and floor of the mouth in 44 (40.7%) patients. Selective neck dissection (SND) I-III was performed unilaterally in 34 patients and bilaterally in 39; SND I-IV was performed unilaterally in 27 patients and bilaterally in two; a combination of SND I-III and I-IV was performed in six patients. Pathologically invaded nodes were detected in 28.7% patients (31/108) and 12/31 had extracapsular spread. TT ranged from 1mm to 24mm (mean 8.2mm) with a mean value of 6.6mm (1–22) in the pN0 group (n =77) and 11.9mm (5–24) in the pN+group (n =31). Patients were found to be pN+ in 0% (0/28), 31.8% (14/44), 31.8% (7/22) and 71.4% (10/14) of cases when TT was <5mm, between 5 and 9mm, between 10 and 14mm, and ⩾15mm, respectively. Conclusions: Based on our retrospective data, the optimal TT cut-off point for prompting prophylactic neck dissection is 5mm. However, larger prospective studies bases on TT measures on preoperative imaging techniques (e.g. MRI or US) are needed before to propose a wait-and-see policy. [Copyright &y& Elsevier]

Summary: The detection of distant metastases is critical for prognostication and for the choice of treatment in patients with head and neck squamous cell carcinoma (HNSCC). Pretreatment screening for distant metastases should be conducted particularly for patients with high risk factors, prior to locoregional treatment decisions. Different diagnostic techniques are discussed. Unfortunately, most studies lack sufficient follow-up to reliably assess false-negative results. Moreover, the designs of most studies vary substantially with regard to homogeneity of groups (tumor types and stages), timing (pretreatment, follow-up) and definition of risk factors (patient selection). Therefore, only a few studies are comparable. The combination of F-18 fluoro-d-glucose-positron emission tomography (FDG-PET) and a dedicated CT (at least of the chest) is the most important imaging protocol at the present time. Eventually, whole-body-MRI (WB-MRI) may possibly replace PET-CT for screening patients for distant metastases. [ABSTRACT FROM AUTHOR]

Summary: Distant metastases from head and neck squamous cell carcinoma (HNSCC), though rare at initial presentation, remain an important manifestation of cancer recurrence and mortality. Although generally considered incurable with a dismal prognosis despite palliative therapy, highly selected patients with distant metastases may have a long term survival benefit from aggressive surgery or radiotherapy. Advances in systemic treatments also may improve patient survival. This article reviews the current state of management of HNSCC patients with distant metastases. [ABSTRACT FROM AUTHOR]

Background and purpose: Although computed tomography (CT) remains the imaging modality of reference in head and neck squamous cell carcinoma (HNSCC) for the three-dimensional (3D) conformal radiotherapy, its poor soft tissue contrast can hamper precisely delineate the tumor volume. Besides anatomical imaging, 2-[18F] fluoro-2-deoxy-d-glucose-positron emission tomography (FDG-PET) has been shown to enhance the accuracy of the tumor delineation but l-methyl [11C]-methionine-positron emission tomography (MET-PET) has never been tested for this purpose. This study was undertaken to determine the potential added value of MET-PET for the delineation of gross target volume (GTV) in HNSCC, as compared to CT and FDG-PET.Patients and methods: Twenty-three patients (10 oropharynx, 8 larynx and 5 hypopharynx) presenting with stage II–IV HNSCC were prospectively enrolled. They were treated by primary radiotherapy or by total laryngectomy. Images (CT, FDG-PET and MET-PET) were acquired with a thermoplastic mask and after coregistration, tumor volumes were delineated on CT and using an adaptative threshold-based automatic method on FDG- and MET-PET. Absolute volumes as well as the mismatch between modalities were compared.Results: For oropharyngeal lesions, FDG volumes were significantly smaller (19.43 ml±21.36) than CT (29.04 ml±30.97) (P=0.013). On the other hand, MET volumes (24.36 ml±20.59) were not different from CT volumes. Similar results were found for laryngeal and hypopharyngeal tumors, with volume of 24.93 ml±19.02 for CT, 21.84 ml±15.32 for MET-PET and 14.49 ml±11.3 for FDG-PET (P=0.003). Large mismatches were observed between modalities, in particular between CT and PET.Conclusions: Our study confirms that the use of FDG-PET may result in a significant reduction of GTV''s as compared to CT. On the contrary, MET-PET does not have any additional value since MET volumes are not different from CT volumes, probably because of the high uptake of MET by the normal mucosa and salivary glands surrounding the tumor. [Copyright &y& Elsevier]