頭頸部癌手術前の嚥下機能評価と術前および術中の介入の意義

Background Early diagnosis of head and neck cancer (HNC) will improve patient outcomes. The low incidence of HNC renders its detection challenging for a general practitioner (GP) in primary health care (PHC). Patients and methods To examine these challenges, our cohort consisted of all patients visiting PHC centres in the City of Helsinki in 2016. We chose 57 ICD-10 codes representing a sign or symptom resulting from a possible HNC and compared data for all new HNC patients. Results A total of 242,211 patients (499,542 appointments) visited PHC centres, 11,896 (5%) of whom presented with a sign or symptom possibly caused by HNC. Altogether, 111 new HNCs were diagnosed within the Helsinki area, of which 40 (36%) were referred from PHC. The median delay from the initial PHC visit to the referral to specialist care was 5 days, whereby 88% of patients were referred within one month. Conclusions Despite the low incidence of HNC and the large number of patients presenting with HNC-related symptoms, GPs working in PHC sort out potential HNC patients from the general patient group in most cases remarkably effectively. KEY MESSAGES For every head and neck cancer (HNC) patient encountered in the primary health care, a general practitioner (GP) will meet approximately 6000 other patients, 100 of whom exhibit a sign or a symptom potentially caused by a HNC. Despite the low incidence of HNC, GPs referred patients to specialist care effectively, limiting the median delay from the initial appointment to referral to only 5 days.

6073 Background: Cisplatin/infusional 5-fluorouracil chemotherapy is routinely administered as standard induction chemotherapy in advanced HANC. However, the optimum treatment remains to be defined. Gemcitabine is an active agent in HANC and few studies have evaluated induction GC in HANC. We have explored the activity and toxicity of GC as induction treatment in HANC and report the results. Methods: From August 2005 to September 2006, 55 patients with locally advanced HANC had induction chemotherapy with GC at Shaukat Khanum Memorial Cancer Hospital and Research Centre. We reviewed the medical records and prospectively collected data to determine activity and toxicity of induction GC. M:F ratio was 64%:36% with a median age of 50 years (range 19–80). All patients had histologically confirmed squamous cell carcinoma. The site of disease was nasopharynx, paranasal sinuses, oral cavity, oropharynx, larynx and hyopharynx in 4% (2), 11% (6), 51% (21), 2% (1), 11% (6) and 22% (11) respectively. According to AJCC staging 7% (4) had stage III and 93% (51) had stage IVa/IVb disease (T3N0 7%, T3N+ 2%, T4N0 38% and T4N+ 53%). Induction chemotherapy consisted of 2 cycles of cisplatin 75 mg/m2 day 1 and gemcitabine 1000 mg/m2 day 1 and 8 with treatment repeated three weekly. Fifty-three (94%) patients received 2 cycles as planned. Toxicity was scored after each cycle according to the NCI.CTC criteria. Response was assessed following completion of induction chemotherapy by clinical examination/MRI scan. Results: All patients were available for assessment of toxicity and response. A total of 111 cycles were delivered. The response rates are: complete 24% (13), partial 62% (34), no response 7% (4) and progression 7% (4). The overall response rate was 86% (complete 24%, partial 62%). No treatment related deaths occurred. Haematological G3/G4 toxicity included neutropenia (13%/7%) and thrombocytopenia (5%/0%). The non-haematological toxicity observed (nausea, vomiting and diarrhoea) was only G1/G2. Conclusions: GC is well tolerated with low toxicity and high anti tumour activity as neoadjuvant chemotherapy treatment in squamous cell head and neck cancer. Combination GC arm should be included in future trials. No significant financial relationships to disclose.

Purpose. To test the hypothesis that head and neck cancer (HNC) patients are in need of specialized follow-up (FU). This was done by an evaluation of the FU activities in a cohort of patients followed longitudinally for five years with focus on optimal duration and interval of post-therapeutic follow-up.Methods. The study evaluated a cohort consisting of 197 consecutive patients with HNC treated at Aarhus University Hospital from 1 January to 31 December 2009. The inclusion criteria was that patients should be deemed free of disease two months after completed primary curative intended treatment or after primary curative salvage. It left 141 patients available for analysis. Data were collected through a medical chart review and from the Danish Head and Neck Cancer Group (DAHANCA) database. Parameters recorded were: regular or extraordinary visit, alarm symptoms, late morbidity and the consequences of these.Results. The 141 patients underwent 1408 FU visits. Only 15 of the 141 patients had no tumor problems or morbidity issues raised at any FU visit. Suspicion of recurrent disease was observed at 207 of the 1408 FU visits, involving 97 patients and resulted in a total of 370 diagnostic procedures; 170 (82%) visits with suspicion of recurrence occurred within 3½ years after end of treatment. A recurrence was verified in 30 patients. Additionally four new primary head and neck cancer was diagnosed during follow-up. There were 1150 visits (82%) involving 135 patients in which late treatment-related morbidity was recorded. Actions taken related to morbidity happened in 71 patients, but no new problems appeared after three years.Conclusion. The study document the need of specialized FU, as 86% of all HNC survivors have tumor or severe morbidity issues during FU. The data suggest that 3½-year FU after ended therapy may be sufficient for the majority of patients.

Cooperative care is a relatively new treatment model that seeks to improve quality, conserve resources, and manage chronic conditions by providing patient and carepartner education in a homelike setting. Support from health care professionals is immediately available as patients and carepartners learn the skills needed to manage a disease and its treatment. This study sought to describe the effect of cooperative care on the treatment of head and neck cancer. Grounded theory methodology and focused interviews of 21 participants were used to answer three research questions: (1) Do the patients, carepartners, and providers involved in cooperative care perceive the potential psychosocial and self-care benefits? (2) How does the cooperative care treatment model affect the achievement of self-care for patients with surgical treatment of head and neck cancer? (3) What are appropriate theories regarding the benefits of cooperative care in the treatment of head and neck cancer that can be tested with quantitative methods? Results indicate that providers perceived cooperative care as a time-consuming process that resulted in less anxious, more communicative patients who required fewer post-discharge resources. Patients and carepartners perceived cooperative care as an experience that took away their fear by providing self-care education within a caring community.

BackgroundWith an increase in the incidence of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) and more favourable survival outcomes, there is now a population of head and neck cancer survivors that are different from preceding decades. In addition, their long-term survivorship issues have become increasing research interests. This study was undertaken to determine the changing epidemiological trends of head and neck cancer survivors in Alberta to better anticipate future demands on healthcare services.MethodsThe Alberta Cancer Registry was queried for adult (aged > 18 years), head and neck cancer (HNC) patients who were at least 1-year post-treatment completion between 1997 to 2016. Cutaneous head and neck and thyroid cancer patients were excluded. Extracted data was then used to calculate the incidence and prevalence of early (< 5 years from treatment), intermediate (5 to < 10 years from treatment), and late (> 10 years from treatment) survivors of head and neck cancer. Point prevalence of HNC survivors in 2005, 2010, and 2015 were then further stratified by gender, sub-site and age.ResultsOver this time period, head and neck cancer survivors tended to be younger (64.0 vs. 62.1, p = 0.046) and male (M:F 2.45:1 vs 2.54:1). In 1997, the predominant subsites were the oral cavity and larynx at 45.8% and 30.9%, respectively. In 2015 the predominant subsites were the oral cavity and oropharynx at 33.0% and 29.4%, respectively. Within the cohort, the prevalence of late HNC survivors increased to 13.3 per 100,000 people in 2015.ConclusionsThere is a significant population of head and neck survivors who are younger, male, and more than 10 years post-treatment. While oral cavity cancers have shown stable disease prevalence in recent decades, the number of OPSCC survivors have increased. With an improved understanding of the distribution and characteristics of HNC survivors, a more guided healthcare support network can be fostered for these patients.

Introduction Head and neck cancer (HNC) is notoriously difficult to treat and the five-year survival rate has improved very little over the past thirty years. Head and neck squamous cell carcinomas (HNSCC) mouse models are invaluable tools for furthering mechanistic HNC research. Molecular imaging (MI) is a promising new modality that may improve current HNC mouse models. Visible florescent proteins (VFPs) have been widely used with animal models for tumor detection using MI. However, the low emission wavelength of VFP results in its overlapping with the auto-fluorescence of many tissues and causes insufficient penetration into deeper tissues, preventing the application of VFP to track local and metastatic tumor progressions. The recent development of infrared-fluorescent protein (IFP) with Biliverdin as a chromophore has greatly advanced in vivo molecular imaging of deep tissues in animals. Hypothesis The ultimate goal of this study is to develop a novel orthotopic mouse model of HNC with regional spreading and distant metastasis tumors that closely mimics human HNC and can be accurately detected by a noninvasive IFP-based molecular imaging (MI) system. Methods A stable human HNC cell line expressing IFP was established. This stable cell line was used for generating a mouse model with HNC. The tumor formation and tumor progression with this model were accurately monitored by a MI system. Results The IFP signal was clearly detected in our mouse model of HNC. Scanned imaging demonstrated a progression pattern of tumor growth in this model. The tumor can be detected earlier with molecular imaging than by conventional external caliper measurement. Unlike surgical measurement, the tumor can be quantified without disturbing the tumor environment. More important, our data suggest that local-regional metastasis tumors can be detected with this model. Conclusion This novel animal model represents an orthotopic human HNC model. The IFP signals penetrate tissues well and can be detected in the deep tissues with this model. Thus, our model has the potential to be used for monitoring tumor spreading and metastasis of advanced stage HNC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4051. doi:1538-7445.AM2012-4051

In addition to changes in facial morphology, head and neck cancer treatment can impact the facial expression. Quantification of changes in facial expression, particularly of smiling, would enable a deeper understanding of the relationship between physical changes and psychosocial adjustment in patients being treated for facial cancer. This study proposes 48 quantitative facial expression measures, which consist of the length normalized distances and slopes between 27 manually annotated fiducial points on standard 2D clinical photographs of patients with head and neck cancer. Using the proposed measures, the maximum intensity of smiling for patients with head and neck cancer prior to their treatments was compared to that of a sample from a healthy population. A total of 7 facial expression measures captured statistically significant differences between patients with head and neck cancer and healthy individuals. These measures suggest that patients with head and neck cancer are less expressive than people without head and neck cancer. This study is the first attempt to quantify the facial expression of patients with head and neck cancer and to build a foundation for studying how surgical interventions may affect their facial expressions. Moreover, this study lays the groundwork for future investigation of the relationship between facial expression and psychosocial adjustment in cancer patients.

6058 Background: HIV-infected individuals have a higher incidence of oral infection with human papillomavirus (HPV) and possibly a higher incidence of head and neck cancer (HNC). Whether this observation reflects defects in the ability of this Òimmune-compromisedÓ patient population to mount sufficient tumor specific immune responses and/or reflects activation of immune escape mechanisms is not known. To address this question, we investigated the expression of HLA class I antigen processing machinery (APM) components and PD-1:PD-L1 pathway activation in HIV(+) HNC patients. Methods: 62 HIV(+) HNC patients diagnosed between 1991-2011 from five tertiary care referral centers in the United States and matched HIV(-) HNC controls were identified. HLA class I APM component, PD-1, and PD-Ll expression were analyzed by immunohistochemical staining. Clinical data was abstracted from the medical records. Results: 44 of 62 (71%) HIV(+) HNC cases were matched based on gender, age ( &lt; 10 years), and anatomic sub-site to HIV(-) HNC patients. There was no significant difference between the cases and controls in HLA-A, HLA-B/C, LMP2, and TAP1, as well as PD-1 and PD-L1 expression. Overall, 62% of all subjects had high PD-1 expression and 82% of the subjects expressed PD-L1. HLA-A, HLA-B/C, and LMP2 expression was significantly correlated with moderate to high PD-1 expression in the HIV(+) HNC cases (p = 0.004, p = 0.026, and p = 0.006, respectively) but not in the HIV(-) controls. Similarly, HLA-A expression was also significantly associated with PD-L1 expression only in the HIV(+) HNC cases (p = 0.029). Conclusions: No defects were detected in the expression of the HLA class I APM components tested. PD-1:PD-L1 pathway was found to be upregulated in both HIV(+) and HIV(-) HNC patients. Our data suggest that recently approved anti-PD-1 immunotherapy should not exclude HIV(+) patients.

Acceleration of diagnosis and initiation of treatment for head and neck cancer requires optimal organization and multidisciplinary collaboration. A project at the Head and Neck Oncology Centre, Aarhus University Hospital aimed at accelerating patient flow. Material and methods. Initiatives were implemented throughout the year 2007. Focus was on optimizing logistics for all patients referred to the center with suspected head and neck cancer. Initiatives included a full-time case manager, pre-booked slots for clinical work-up and weekly tumor-boards. Key-dates were registered and relevant intervals were quantitatively evaluated and compared to a reference-group from 2006. Results. We registered 446 patients. Waiting times for first clinical examination on ENT department were reduced from median eight to median two days through 2007 (p < 0.0001). Time from first clinical examination and until referral for treatment was reduced from median 21 to median nine days (p < 0.0001). Time from referral to treatment and until initiation of treatment was reduced from median 26 to median 15 days (p < 0.001). The net result of these reductions was a reduced overall time from median 57 days ultimo 2006 to median 29 days ultimo 2007 (p < 0.0001). Conclusion. The current project has shown that it is possible to reduce waiting times in head and neck cancer. Through logistic changes, employment of a full-time case manager, strengthening the multidisciplinary tumor board and giving higher priority for head and neck cancer patients, the overall time from first suspicion of cancer until treatment start was reduced from 57 calendar days to 29 calendar days.

Systemic chemotherapy is increasingly being used with radiotherapy for the radical treatment of advanced head and neck cancers. Chemotherapy offers modest benefits in the metastatic setting. Platinum containing agents are the most active drugs and form the mainstay of most chemotherapy schedules. In recent years taxanes have shown activity in head and neck cancers and are being ­incorporated into neo-adjuvant and concomitant chemotherapy regimens. Targeted agents and epidermal growth factor receptor (EGFR) inhibitors, like cetuximab, in particular, have shown benefit in the metastatic and the concomitant setting. EGFR inhibitors and other targeted agents form the thrust of pre-clinical and clinical research into the systemic treatment of head and neck cancers.

The number of new cases of oral cavity, pharynx and larynx cancers is estimated be 52,610 in 2012 with an expected 11,500 deaths. Despite progressive improvements in outcome, current treatment approaches still result in an overall survival rate of approximately 50% at five years for locally advanced head and neck cancer (HNC). Additional therapeutic approaches are needed to further enhance outcomes. NAD(P)H:quinone oxidoreductase 1 (NQO1) is a two-electron oxidoreductase that reduces quinones to hydroquinones and has been shown to be overexpressed in a number of solid tumors. For the first time, our studies in 45 HNC cell lines identified NQO1 overexpression in more than 70% of HNC cell lines. Furthermore over-expression of NQO1 has been shown to be a critical determinant for tumor-selective therapy using β-lapachone (β-lap), a substrate of NQO1 that undergoes partial reduction and spontaneous reversion, creating a futile cycle that produces very high levels of reactive oxygen species. HNC cell lines that overexpress NQO1 are significantly killed by treatment with β-lap. The anti-cancer action of β-lap in HNC cells is initiated and processed through five essential downstream mediators: (i) reactive oxygen species (ROS), particularly hydrogen peroxide (H2O2); (ii) DNA single strand breaks (SSBs) induced by ROS; (iii) hyperactivation of poly(ADP-ribose)polymerase-1 (PARP1) and accompanying poly(ADP-ribose)-PARP1 (PAR) formation; (iv) dramatic NAD+/ATP depletion; and (v) programmed necrosis (necroptosis). In combination with ionizing radiation (IR), β-Lap radiosensitized NQO1(+) HNC cells under conditions where nontoxic doses of either agent alone did not achieve threshold levels of DNA lesions and /or SSBs required for PARP-1 hyper-activation. Furthermore, combination therapy with β-lap and IR significantly enhanced γ-H2AX and 53BP1 foci formation and PARP-1 hyper-activation which was associated with ATP loss and induction of programmed cell death. Furthermore, the anticancer effects of combination β-Lap and IR were blocked by the NQO1 inhibitor dicoumarol. Our findings offer a strategy for the clinical utilization of β-lap as a radiosensitizer in HNC. Citation Format: Long Shan Li, Srilakshmi Reddy, Jinming Gao, David A. Boothman, Baran Sumer, John S. Yordy. NQO1-dependent anticancer action with combination β-lapachone and ionizing radiation in the head and neck cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 589. doi:10.1158/1538-7445.AM2013-589

The purpose of this study was to determine the phenotyping of Peripheral Blood Lymphocytes (PBL) in Head and Neck Cancers (HNCA) patients and to relate this with the level of Cell-Mediated Immunity (CMI) measured by in vitro lymphoproliferative assay, in order to evaluate immune suppression in HNCA patients and its possible mechanisms. Accordingly, one hundred twenty two HNCA patients and 100 control subjects were enrolled in this study. HNCA patients were classified into 42 nasopharyngeal carcinoma, 66 carcinoma of larynx and 14 Hypo Pharyngeal Carcinoma (HPC). For measuring CMI, Microculture Tetrazolium assay (MTT) was applied on the freshly isolated lymphocytes of HNCA patients and control group. Immunophenotyping of PBL was carried out for monitoring the blood level of CD3+, CD4+, CD8+, CD21+ cells in HNCA patients in comparison with controls. The results of both assays have been integrated, revealed the presence of remarked immune suppression in HNCA patients in comparison with the controls, especially for NasoPharyngeal Carcinoma (NPC) patients who were immunosuppressed more than other studied HNCA types. Surprisingly, NPC group showed the lowest CMI level along with the highest level of PBL subsets, particularly NPC patients expressed the highest level of CD8+ cells among HNCA. It was inferred that CD8+ cells were more likely immune suppressor rather than cytotoxic cells and this is the principal factor for inducing sustained immunosuppression in HNCA and in NPC in particular. Furthermore CD4/CD8 ratio proved to be a reliable index for assessing the immunological status of HNCA patients and more dependable index than other immunity-evaluating factors.

Risk of second primary cancer among patients with head and neck cancers: a pooled analysis of 13 cancer registries

This thesis deals with the topic of head and neck cancer (HNC) follow-up from a health economics perspective. Despite recent advances in treating primary HNC, the long-term prognosis of these patients is still poor due to a high risk of cancer recurrence. Until now, there is no agreement about the best way of monitoring patients after the end of therapies. Moreover, patients’ preferences for alternative surveillance schemes are unknown. A multicentre randomized controlled trial comparing two follow-up strategies of different intensity is currently ongoing in Italy. This thesis aims at filling some of the literature “gaps” around HNC surveillance, using Italy as a case study. The first chapter introduces the topic. The second chapter is a systematic literature review and critical appraisal of economic evaluation studies of post-treatment follow-up programs in any cancer type. The third chapter is a systematic literature review and quality appraisal of studies reporting original health state utility values in HNC, with a focus on articles addressing the post-treatment phase. The fourth chapter maps the EuroQol 5-Dimension 5-Level (EQ-5D-5L) utility values from two cancer-specific measures developed by the European Organization for Research and Treatment of Cancer (EORTC) by using a variety of regression techniques (linear, Tobit, mixture models) and several EQ-5D-5L country tariff sets; the developed functions are useful to inform future economic evaluations in HNC. The fifth chapter presents an exploratory model-based economic evaluation of the two follow-up strategies under investigation in the trial, where an intensive program of radiological assessments is compared to a symptom-driven surveillance; the cost analysis is conducted from a regional healthcare system perspective in Italy. Lastly, the sixth chapter presents a discrete choice experiment using best-worst scaling to elicit patients’ preferences during follow-up at the National Cancer Institute (Milan, Italy).

In ongoing reviews of 339 patients with surgically treated primary squamous cell carcinoma, there were 19 (5.6%) with concurrent gastric cancer and 11 (3.2%) with head and neck cancer. The incidences of intra-esophageal multiple occurrence of esophageal cancer are 27.3% and 26.3% in those with associated head and neck cancer and gastric cancer, respectively, and higher than 7.1% in those without such a concurrent cancer. There was no difference in the clinicopathological characteristics of those with concurrent head and neck and gastric cancers, except for the higher incidence of metachronous occurrence in the former. These findings suggest that, in cases of esophageal cancer associated with concurrent head and neck cancer and gastric cancer, intraesophageal multiplicity of the esophageal carcinoma is frequent and that preoperative serial evaluations is most important to design treatment and estimate the prognosis.