Alpha B-crystallin, a new independent marker for poor prognosis in head and neck cancer

Objectives. Gene expression profiling has provided many insights into tumor progression but translation to clinical practice has been limited. We have previously identified a list of potential markers by the differences of expression profiling of seven matched head and neck cancer (HNSCC) tumors with autologous normal oral mucosa (NOM). Alpha B-crystallin (CRYAB) was in the top 5% of genes identified with statistically significant differences in expression between tumor and NOM at the mRNA level. The objective was to confirm this in routine paraffin sections at the protein level. Study Design: The level of alpha B-crystallin was determined in tumors of 62 HNSCC patients whose prognosis was known for 5 years. Methods. Immunohistochemical detection of alpha B-crystallin expression was performed on HNSCC paraffin sections. Results. Univariate survival analysis identified lack of alpha B-crystallin staining as an independent prognostic marker for disease-free interval (P < 0.001) and overall survival (P < 0.002) of HNSCC patients over the 5-year observation period. Notably, all 13 patients (100%), including 5 patients with nodal disease whose tumors lacked alpha B-crystallin had no recurrences (P < 0.001). Nineteen of 27 node-negative patients stained positive for alpha B-crystallin and seven of the 19 (36.8%) had recurrences. Conclusion: Presence or absence of expression of alpha B-crystallin was a powerful marker for prognosis in this series of patients.

Chemoprevention of head and neck cancer with retinoids: a negative result

Objective: To determine whether isotretinoin (or 13-cis-retinoic acid) decreases the risk of second primary cancers in patients previously treated for cure of head and neck squamous cell carcinoma. Design: Randomized, double-blind, placebo-controlled trial. Setting: Two head and neck multidisciplinary cancer clinics in university teaching hospitals taking cases from 4 to 5 million people in Queensland, Australia, combined to,enter appropriate patients into this trial. Patients: One hundred fifty-one patients with their first head and neck squamous cell carcinoma treated with high expectation for cure and living close by. They were randomized into 3 arms to receive 3 years of treatment. Interventions: Patients took isotretinoin at a high dose (1.0 mg/kg per day) or a moderate dose (0.5 mg/kg per day) or placebo. Group 1 took the high dose for I year and then the moderate dose for 2 years. Group 2 took the moderate dose for 3 years. Group 3 took placebo for 3 years. Main Outcome Measures: The diagnosis of a second primary malignancy of the head and neck, lung, or bladder was regarded as the end point signifying failure of therapy. Issues of drug adverse effect profile and impact on survival were measured. Results: There was no significant difference in the occurrence of second primary disease (P=.90), the recurrence of primary disease (P=.70), or disease-free time (P=.80) between the treatment and nontreatment arms. Numbers were too small to find differences in survival. Conclusion: With evidence that retinoid treatment adversely affects survival of lung cancer and with this drug not significantly decreasing the incidence of second primary tumors of head and neck squamous cell carcinoma, the use of this drug in head and neck cancer patients for second cancer prophylaxis is not indicated.

Head and neck cancer: past, present and future

Head and neck cancer consists of a diverse group of cancers that ranges from cutaneous, lip, salivary glands, sinuses, oral cavity, pharynx and larynx. Each group dictates different management. In this review, the primary focus is on head and neck squamous cell carcinoma (HNSCC) arising from the mucosal lining of the oral cavity and pharynx, excluding nasopharyngeal cancer. Presently, HNSCC is the sixth most prevalent neoplasm in the world, with approximately 900,000 cases diagnosed worldwide. Prognosis has improved little in the past 30 years. In those who have survived, pain, disfigurement and physical disability from treatment have had an enormous psychosocial impact on their lives. Management of these patients remains a challenge, especially in developing countries where this disease is most common. Of all human cancers, HNSCC is the most distressing since the head and neck is the site of the most complex functional anatomy in the human body. Its areas of responsibility include breathing, the CNS, vision, hearing, balance, olfaction, taste, swallowing, voice, endocrine and cosmesis. Cancers that occur in this area impact on these important human functions. Consequently, in treating cancers of the head and neck, the effects of the treatment on the functional outcome of the patient need the most serious consideration. In assessing the success of HNSCC treatment, consideration of both the survival and functional deficits that the patient may suffer as a consequence of their treatment are of paramount importance. For this reason, the modern-day management of head and neck patients should be carried out in a multidisciplinary head and neck clinic.

Low frequency of cigarette smoking and the risk of head and neck cancer in the INHANCE consortium pooled analysis

Funding • The pooled data coordination team (PBoffetta, MH, YCAL) were supported by National Cancer Institute grant R03CA113157 and by National Institute of Dental and Craniofacial Research grant R03DE016611 • The Milan study (CLV) was supported by the Italian Association for Research on Cancer (Grant no. 10068). • The Aviano study (LDM) was supported by a grant from the Italian Association for Research on Cancer (AIRC), Italian League Against Cancer and Italian Ministry of Research • The Italy Multicenter study (DS) was supported by the Italian Association for Research on Cancer (AIRC), Italian League Against Cancer and Italian Ministry of Research. • The Study from Switzerland (FL) was supported by the Swiss League against Cancer and the Swiss Research against Cancer/Oncosuisse [KFS-700, OCS-1633]. • The central Europe study (PBoffetta, PBrenan, EF, JL, DM, PR, OS, NS-D) was supported by the World Cancer Research Fund and the European Commission INCOCOPERNICUS Program [Contract No. IC15- CT98-0332] • The New York multicentre study (JM) was supported by a grant from National Institute of Health [P01CA068384 K07CA104231]. • The study from the Fred Hutchison Cancer Research Center from Seattle (CC, SMS) was supported by a National Institute of Health grant [R01CA048996, R01DE012609]. • The Iowa study (ES) was supported by National Instituteof Health [NIDCR R01DE011979, NIDCR R01DE013110, FIRCA TW001500] and Veterans Affairs Merit Review Funds. • The North Carolina studies (AFO) were supported by National Institute of Health [R01CA061188], and in part by a grant from the National Institute of Environmental Health Sciences [P30ES010126]. • The Tampa study (PLazarus, JM) was supported by National Institute of Health grants [P01CA068384, K07CA104231, R01DE013158] • The Los Angeles study (Z-F Z, HM) was supported by grants from National Institute of Health [P50CA090388, R01DA011386, R03CA077954, T32CA009142, U01CA096134, R21ES011667] and the Alper Research Program for Environmental Genomics of the UCLA Jonsson Comprehensive Cancer Center. • The Houston study (EMS, GL) was supported by a grant from National Institute of Health [R01ES011740, R01CA100264]. • The Puerto Rico study (RBH, MPP) was supported by a grant from National Institutes of Health (NCI) US and NIDCR intramural programs. • The Latin America study (PBoffetta, PBrenan, MV, LF, MPC, AM, AWD, SK, VW-F) was supported by Fondo para la Investigacion Cientifica y Tecnologica (FONCYT) Argentina, IMIM (Barcelona), Fundaco de Amparo a‘ Pesquisa no Estado de Sao Paulo (FAPESP) [No 01/01768-2], and European Commission [IC18-CT97-0222] • The IARC multicentre study (SF, RH, XC) was supported by Fondo de Investigaciones Sanitarias (FIS) of the Spanish Government [FIS 97/ 0024, FIS 97/0662, BAE 01/5013], International Union Against Cancer (UICC), and Yamagiwa-Yoshida Memorial International Cancer Study Grant. • The Boston study (KKelsey, MMcC) was supported by a grant from National Institute of Health [R01CA078609, R01CA100679]. • The Rome study (SB, GC) was supported by AIRC (Italian Agency for Research on Cancer). • The US multicentre study (BW) was supported by The Intramural Program of the National Cancer Institute, National Institute of Health, United States. • The Sao Paolo study (V W-F) was supported by Fundacao de Ampara a Pesquisa no Estado de Sao Paulo (FAPESP No 10/51168-0) • The MSKCC study (SS, G-P Y) was supported by a grant from National Institute of Health [R01CA051845]. • The Seattle-Leo stud (FV) was supported by a grant from National Institute of Health [R01CA030022] • The western Europe Study (PBoffetta, IH, WA, PLagiou, DS, LS, FM, CH, KKjaerheim, DC, TMc, PT, AA, AZ) was supported by European Community (5th Frame work Programme) grant no QLK1-CT-2001- 00182. • The Germany Heidelberg study (HR) was supported by the grant No. 01GB9702/3 from the German Ministry of Education and Research.

AN INVESTIGATION ON ROUTINE FOLLOW-UP CARE FOR HEAD AND NECK CANCER

BACKGROUND: Follow-up care aims to provide surveillance with early detection of recurring cancers and to address treatment complications and other health issues in survivorship. It is assumed that follow-up care fulfills these aims, however little evidence supports routine surveillance detecting curable disease early enough to improve survival. Cancer survivors are a diverse patient population, suggesting that a single follow-up regimen may not meet all patients’ follow-up needs. Little is known about what effective follow-up care should include for head and neck cancer patients in a Canadian setting. Identification of subgroups of patients with specific needs and current practices would allow for hypotheses to be generated for enhancing follow-up care. OBJECTIVES: 1a) To describe the follow-up needs and preferences of head and neck cancer patients, 1b) to identify which patient characteristics predict needs and preferences, 1c) to evaluate how needs and preferences change over time, 2a) to describe follow-up care practices by physician visits and imaging tests, and 2b) to identify factors associated to the delivered follow-up care. METHODS: 1) 175 patients who completed treatment between 2012 and 2013 in Kingston and London, Ontario were recruited to participate in a prospective survey study on patients’ needs and preferences in follow-up care. Bivariate and multivariate analyses were employed to describe patient survey responses and to identify patient characteristics that predicted needs and preferences. 2) A retrospective cohort study of 3975 patients on routine follow-up from 2007 to 2015 was carried out using data linkages across registry and administrative databases to describe follow-up practices in Ontario by visits and tests. Multivariate regression analyses assessed factors related to follow-up care. RESULTS: 1) Patients’ needs and preferences were wide-ranging with several characteristics predicting needs and preferences (ORECOG=2.69 and ORAnxiety=1.13). Needs and preferences declined as patients transitioned into their second year of follow-up (p<0.05). 2) Wide variation in practices was found, with marked differences compared to existing consensus guidelines. Multiple factors were associated with follow-up practices (RRTumor site=0.73 and RRLHIN=1.47). CONCLUSIONS: Patient characteristics can be used to personalize care and guidelines are not informing practice. Future research should evaluate individualized approaches to follow-up care.

The Role of Perceived Social Support, Resilience, and Depression on Communicative Participation in Head and Neck Cancer Survivors

Thesis (Master's)--University of Washington, 2016-08

CAREGIVING FOR A FAMILY MEMBER WITH HEAD AND NECK CANCER

Objective: To know the perception of informal caregivers regarding the care for a family member with head and neck cancer. Methods: Qualitative study conducted between March and May 2014 in the radiotherapy outpatient center of the Centro de Alta Complexidade em Oncologia – CACON (Oncology High Complexity Center) of the Hospital Universitário de Brasília – HUB (University Hospital of Brasília) using semi-structured interviews with nine caregivers about the experience of caring for family members. Data underwent Content Analysis and four units of meaning were identified: “Representation of cancer in the Family”, “The care as debt, individual reward or reconstruction of family ties”, “Repercussions of cancer on the caregiver’s personal life” and “Social support and network used by caregivers”. Results: Feelings of sadness and surprise at the moment of diagnosis were attributed to cancer, as well as the idea of punishment. The care was seen as personal satisfaction, accomplishment and opportunity for family rapprochement. Work overload and change in routine were altered functions. Religiosity, exchange of experience in the waiting room and institutional support appeared as coping strategies. Conclusion: The experience of caring for family members with head and neck cancer directly interferes in the lives of caregivers. Pointing out the institutional embracement as a strategy within the social network reinforces the importance of integrating the caregivers as a significant part of the health care plan developed by the health team.

Weekly cisplatin concurrently with radiotherapy in head and neck squamous cell cancer : a retrospective analysis of a tertiary institute experience

Radiotherapy combined with three weekly 100 mg/m2 of cisplatin is the accepted standard of care in head and neck squamous cell carcinoma. However, this regimen is associated with severe toxicities with devastating effects on patients. Alternative protocols like weekly 40 mg/m2 have been used in an attempt to reduce toxicities. The main objective of the present study is to identify the dose intensities and toxicities of weekly cisplatin in patients treated in a tertiary centre over a 12 month period. Included patients had squamous cell carcinoma arising in the oral cavity, oropharynx, larynx, or hypopharynx. Patients were excluded if they had nasopharyngeal squamous cell carcinoma, distant metastasis or if they had prior treatment for head and neck cancer excluding neck dissection. During the study period, 52 patients met the inclusion criteria and their data were retrospectively obtained from the patients' database of St James hospital, Dublin. The median age of the study cohort was 54 years (range 33-73). Of the patients, 40 (76.9 %) were male and 12 (20.1 %) were female. The primary tumour sites were as follows: oral cavity and oropharynx in 38 (73 %), larynx in 10 (19 %), and hypopharynx in 4 (8 %). In total, 33 (63.5 %) patients had stage IV disease, while 19 (36.5 %) had stage III disease. Treatment was definitive in 35 (67 %) patients and adjuvant in 17 (35 %). Full-dose radiotherapy was achieved in 50 (96 %) patients. Only 22 (42.3 %) patients completed the intended six cycles of chemotherapy. Cumulative dose of 200 mg/m2 or more was reached in 37 (71 %) patients. The acute adverse effects included grades 3 and 4 mucositis, which occurred in 22 (43.3 %) and 6 patients (12 %), respectively. Grade 3 and 4 neutropenia occurred in six (11.5 %) and three (5.7 %) patients, respectively. The only other haematological toxicity was grade 3 anaemia in 20 (38.4 %) patients. There was no grade 3 or 4 renal toxicity among the study cohort, although grade 2 was observed in six (11.5 %) patients. Death occurred in one patient due to neutropenic septicaemia. In conclusion, weekly cisplatin is associated with moderate to severe toxicities and might lead to suboptimal chemotherapy delivery. More prospective clinical studies are required to determine the optimal chemoradiation regimen in head and neck squamous cell carcinoma.

Association of CYP1B1 codon 432 mutant allele in head and neck squamous cell cancer is reflected by somatic mutations of p53 in tumor tissue

Tobacco use is causally associated with head and neck squamous cell cancer (HNSCC). Here, we present the results of a case-control study that investigated the effects that the genetic variants of the cytochrome (CYP)1A1, CYP1B1, glutathione-S-transferase (GST)M1, GSTT1, and GSTP1 genes have on modifying the risk of smoking-related HNSCC. Allelisms of the CYP1A1, GSTT1, GSTM1, and GSTT1 genes alone were not associated with an increased risk. CYP1B1 codon 432 polymorphism was found to be a putative susceptibility factor in smoking-related HNSCC. The frequency of CYP1B1 polymorphism was significantly higher (P < 0.001) in the group of smoking cases when compared with smoking controls. Additionally, an odds ratio (OR) of 4.53 (2.62-7.98) was discovered when investigating smoking and nonsmoking cases for the susceptible genotype CYP1B1*2/*2, when compared with the presence of the genotype wild type. In combination with polymorphic variants of the GST genes, a synergistic-effect OR was observed. The calculated OR for the combined genotype CYP1B1*2/*2 and GSTM1*2/*2 was 12.8 (4.09-49.7). The calculated OR for the combined genotype was 13.4 (2.92-97.7) for CYP1B1*2/*2 and GSTT1*2/*2, and 24.1 (9.36-70.5) for the combination of CYP1B1*2/*2 and GSTT1-expressors. The impact of the polymorphic variants of the CYP1B1 gene on HNSCC risk is reflected by the strong association with the frequency of somatic mutations of the p53 gene. Smokers with susceptible genotype CYP1B1*2/*2 were 20 times more likely to show evidence of p53 mutations than were those with CYP1B1 wild type. Combined genotype analysis of CYP1B1 and GSTM1 or GSTT1 revealed interactive effects on the occurrence of p53 gene mutations. The results of the present study indicate that polymorphic variants of CYP1B1 relate significantly to the individual susceptibility of smokers to HNSCC.

Symptoms of depression in patients with cancer of the head and neck undergoing radiotherapy treatment: a prospective study

This study aimed to investigate the frequency of symptoms of depression in patients with cancer of the head and neck undergoing radiotherapy treatment, in the initial, middle and final stages of the treatment. This is a prospective exploratory quantitative study of 41 patients with head and neck cancer, undergoing radiotherapy treatment in the Oncology Outpatient Clinic of the Beneficencia Portuguese Hospital of Ribeirao Preto. Data were collected through the Beck Depression Inventory instrument, and analyzed quantitatively by means of the Statistical Package for the Social Sciences. Symptoms of dysphoria were found to increase throughout the treatment, as well as the number of patients with depression. The results show the importance for the healthcare professionals to detect the prevalence and the levels of the symptoms of depression, since these symptoms tend to increase and may lead to consequences such as a lack of adherence to treatment and a decrease in the quality of life of these patients.

Aspirin and other non-steroidal anti-inflammatory drug prescriptions and survival after the diagnosis of head and neck and oesophageal cancer

Peer reviewed

Long term survival following the detection of circulating tumour cells in head and neck squamous cell carcinoma

Background Techniques for detecting circulating tumor cells in the peripheral blood of patients with head and neck cancers may identify individuals likely to benefit from early systemic treatment. Methods Reconstruction experiments were used to optimise immunomagnetic enrichment and RT-PCR detection of circulating tumor cells using four markers (ELF3, CK19, EGFR and EphB4). This method was then tested in a pilot study using samples from 16 patients with advanced head and neck carcinomas. Results Seven patients were positive for circulating tumour cells both prior to and after surgery, 4 patients were positive prior to but not after surgery, 3 patients were positive after but not prior to surgery and 2 patients were negative. Two patients tested positive for circulating cells but there was no other evidence of tumor spread. Given this patient cohort had mostly advanced disease, as expected the detection of circulating tumour cells was not associated with significant differences in overall or disease free survival. Conclusion For the first time, we show that almost all patients with advanced head and neck cancers have circulating cells at the time of surgery. The clinical application of techniques for detection of spreading disease, such as the immunomagnetic enrichment RT-PCR analysis used in this study, should be explored further.

Monte Carlo evaluation of collapsed-cone convolution calculations in head and neck radiotherapy treatment plans

The presence of air and bone interfaces makes the dose distribution for head and neck cancer treatments difficult to accurately predict. This study compared planning system dose calculations using the collapsed-cone convolution algorithm with EGSnrcMonte Carlo simulation results obtained using the Monte Carlo DICOMToolKit software, for one oropharynx, two paranasal sinus and three nodal treatment plans. The difference between median doses obtained from the treatment planning and Monte Carlo calculations was found to be greatest in two bilateral treatments: 4.8%for a retropharyngeal node irradiation and 6.7% for an ethmoid paranasal sinus treatment. These deviations in median dose were smaller for two unilateral treatments: 0.8% for an infraclavicular node irradiation and 2.8% for a cervical node treatment. Examination of isodose distributions indicated that the largest deviations between Monte Carlo simulation and collapsed-cone convolution calculations were seen in the bilateral treatments, where the increase in calculated dose beyond air cavities was most significant.

Training program impact on thermoplastic immobilization for head and neck radiation therapy

Purpose: To determine whether uniform guidelines and training in the stabilization and formation of thermoplastic shells can improve the reproducibility of set-up for Head and Neck cancer patients. Methods and materials: Image based measurements of the planning and treatment positions for 35 head and neck cancer patients undergoing radical radiotherapy were analysed to provide a baseline of the reproducibility of thermoplastic immobilization. Radiation therapists (RT) were surveyed to establish a perception of their confidence in thermoplastic procedures. An evidence based staff training program was created and implemented. Set-up reproduction and staff perception were reviewed to measure the impact of the training program. Results: The mean (SD) 3D vectors of anatomical displacement, measured on the patient images, improved from 4.64 (2.03) for the baseline group compared to 3.02 (1.65) following training (p < 0.01). The proportion of 3D displacements of patient data exceeding 5 mm 3D vector was decreased from 37.1% to 5.7% (p < 0.001) and the 3 mm vector from 85.7% to 42.9% (p < 0.001). The post-training survey scores demonstrated improved confidence in reproducibility of set-up for head and neck patients. Conclusion: The Thermoplastic Shells Training Program has been found to improve the treatment reproducibility for head and neck radiation therapy patients. Uniform guidelines have increased RT confidence in thermoplastic procedures.