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1.  Acupuncture for Dysphagia after Chemoradiation Therapy in Head and Neck Cancer: A Case Series Report* 
Integrative cancer therapies  2010;9(3):284-290.
Background
Dysphagia is a common side effect following chemoradiation therapy (CRT) in head and neck cancer (HNC) patients.
Methods
In this retrospective case series, ten HNC patients were treated with acupuncture for radiation-induced dysphagia and xerostomia. All patients were diagnosed with stage III/IV squamous cell carcinoma. Seven of 10 patients were percutaneous endoscopic gastrostomy (PEG) tube-dependent when they began acupuncture. Manual acupuncture and electroacupuncture were used once a week.
Results
Nine of 10 patients reported various degrees of subjective improvement in swallowing functions, xerostomia, pain and fatigue levels. Six (86%) of 7 PEG tube-dependent patients had their feeding tubes removed after acupuncture, with a median duration of 114 days (range 49–368) post CRT. One typical case is described in detail.
Conclusions
A relatively short PEG tube duration and reduced symptom severity following CRT were observed in these patients. Formal clinical trials are required to determine the causality of our observations.
doi:10.1177/1534735410378856
PMCID: PMC3014053  PMID: 20713374
acupuncture; chemoradiation therapy; radiation therapy; head and neck cancer; dysphagia; percutaneous endoscopic gastrostomy (PEG) tube
2.  The effect of neck dissection on quality of life after chemoradiation 
Objective
To determine differences in QOL between head and neck cancer patients receiving chemoradiation versus chemoradiation and neck dissection.
Methods
A prospective cohort study was conducted at 2 tertiary otolaryngology clinics and a VA. Sample: 103 oropharyngeal Stage IV SCCA patients treated via chemoradiation +/− neck dissection. Intervention: self-administered health survey collecting health, demographic, and QOL information pretreatment and 1 year later. Main outcome measures: QOL via SF-36 and HNQoL. Descriptive statistics were calculated for health / clinical characteristics, demographics, and QOL scores. T-tests evaluated changes in QOL over time.
Results
65 patients received chemoradiation and 38 chemoradiation + neck dissection. Only the pain index of the SF-36 showed a significant difference between groups (p<.05) with the neck dissection group reporting greater pain.
Conclusions
After post-treatment neck dissection, patients experience statistically significant decrement in bodily pain domain scores, but other QOL scores are similar to those of patients undergoing chemoradiation alone.
doi:10.1016/j.otohns.2008.07.007
PMCID: PMC2840712  PMID: 18922336
3.  A Unique Complication Associated with Concurrent Chemoradiation for the Treatment of Locally Advanced Head and Neck Cancer 
Clinical Medicine. Oncology  2008;2:313-318.
Background
Concurrent chemoradiation is becoming an increasingly popular treatment for patients with locally advanced head and neck cancer. The full extent of treatment related complications has not been completely documented in the literature.
Methods
We present the case of a patient treated with definitive intensity modulated radiation therapy and concurrent carboplatin and fluorouracil for a locally advanced oral cavity and base of tongue cancer.
Results
The patient suffered acute grade 4 dermatitis and mucositis during treatment. One month after completion of treatment, the patient was found to have permanent adherence of the tongue to the buccal mucosa as a result of severe scar tissue formation.
Conclusions
As more patients undergo chemoradiation for the treatment of locally advanced head and neck cancer, the full extent of treatment related complications are being identified. To our knowledge, this is the first report of chemoradiation for head and neck cancer resulting in adherence of the tongue to the buccal mucosa.
PMCID: PMC3161639  PMID: 21892292
locally advanced head and neck cancer; complications; radiation; chemoradiation; toxicity
4.  Epidermal growth factor receptor targeted therapy in stages III and IV head and neck cancer 
Current Oncology  2010;17(3):37-48.
Question
What are the benefits associated with the use of anti–epidermal growth factor receptor (anti-egfr) therapies in squamous cell carcinoma of the head and neck (hnscc)? Anti-egfr therapies of interest included cetuximab, gefitinib, lapatinib, zalutumumab, erlotinib, and panitumumab.
Perspectives
Head-and-neck cancer includes malignant tumours arising from a variety of sites in the upper aerodigestive tract. The most common histologic type is squamous cell carcinoma, and most common sites are the oral cavity, the oropharynx, the hypopharynx, and the larynx. Worldwide, hnscc is the sixth most common neoplasm, and despite advances in therapy, long-term survival in hnscc patients is poor. Primary surgery followed by chemoradiation, or primary chemoradiation, are the standard treatment options for patients with locally advanced (stages iii–ivb) hnscc; however, meta-analytic data indicate that the benefit of concurrent platinum-based chemotherapy disappears in patients over the age of 70 years.
Cetuximab is a monoclonal antibody approved for use in combination with radiation in the treatment of patients with untreated locally advanced hnscc and as monotherapy for patients with recurrent or metastatic (stage ivc) hnscc who have progressed on platinum-based therapy.
Given the interest in anti-egfr agents in advanced hnscc, the Head and Neck Cancer Disease Site Group (dsg) of Cancer Care Ontario’s Program in Evidence-Based Care (pebc) chose to systematically review the literature pertaining to this topic so as to develop evidence-based recommendations for treatment.
Outcomes
Outcomes of interest included overall and progression-free survival, quality of life, tumour response rate and duration, and the toxicity associated with the use of anti-egfr therapies.
Methodology
The medline, embase, and Cochrane Library databases, the American Society of Clinical Oncology online conference proceedings, the Canadian Medical Association InfoBase, and the National Guidelines Clearinghouse were systematically searched to locate primary articles and practice guidelines. The reference lists from relevant review articles were searched for additional trials. All evidence was reviewed, and that evidence informed the development of the clinical practice guideline. The resulting recommendations were approved by the Report Approval Panel of the pebc, and by the Head and Neck Cancer dsg. An external review by Ontario practitioners completed the final phase of the review process. Feedback from all parties was incorporated to create the final practice guideline.
Results
The electronic search identified seventy-four references that were reviewed for inclusion. Only four phase iii trials met the inclusion criteria for the present guideline. No practice guidelines, systematic reviews, or meta-analyses were found during the course of the literature search.
The randomized controlled trials (rcts) involved three distinct patient populations: those with locally advanced hnscc being treated for cure, those with incurable advanced recurrent or metastatic hnscc being treated with first-line platinum-based chemotherapy, and those with incurable advanced recurrent or metastatic hnscc who had disease progression despite, or who were unsuitable for, first-line platinum-based chemotherapy.
Practice Guideline
These recommendations apply to adult patients with locally advanced (nonmetastatic stages iii–ivb) or recurrent or metastatic (stage ivc) hnscc.
Platinum-based chemoradiation remains the current standard of care for treatment of locally advanced hnscc.
In patients with locally advanced hnscc who are medically unsuitable for concurrent platinumbased chemotherapy or who are over the age of 70 years (because concurrent chemotherapy does not appear to improve overall survival in this patient population), the addition of cetuximab to radical radiotherapy should be considered to improve overall survival, progression-free survival, and time to local recurrence.
Cetuximab in combination with platinum-based combination chemotherapy is superior to chemotherapy alone in patients with recurrent or metastatic hnscc, and is recommended to improve overall survival, progression-free survival, and response rate.
The role of anti-egfr therapies in the treatment of locally advanced hnscc is currently under study in large randomized trials, and patients with hnscc should continue to be offered clinical trials of novel agents aimed at improving outcomes.
Qualifying Statements
Chemoradiation is the current standard of care for patients with locally advanced hnscc, and to date, there is no evidence that compares cetuximab plus radiotherapy with chemoradiation, or that examines whether the addition of cetuximab to chemoradiation is of benefit in these patients. However, five ongoing trials are investigating the effect of the addition of egfr inhibitors concurrently with, before, or after chemoradiotherapy; those trials should provide direction about the best integration of cetuximab into standard treatment.
In patients with recurrent or metastatic hnscc who experience progressive disease despite, or who are unsuitable for, first-line platinum-based chemotherapy, gefitinib at doses of 250 mg or 500 mg daily, compared with weekly methotrexate, did not increase median overall survival [hazard ratio (hr): 1.22; 96% confidence interval (ci): 0.95 to 1.57; p = 0.12 (for 250 mg daily vs. weekly methotrexate); hr: 1.12; 95% ci: 0.87 to 1.43; p = 0.39 (for 500 mg daily vs. weekly methotrexate)] or objective response rate (2.7% for 250 mg and 7.6% for 500 mg daily vs. 3.9% for weekly methotrexate, p > 0.05). As compared with methotrexate, gefitinib was associated with an increased incidence of tumour hemorrhage (8.9% for 250 mg and 11.4% for 500 mg daily vs. 1.9% for weekly methotrexate).
PMCID: PMC2880902  PMID: 20567625
Head-and-neck cancer; epidermal growth factor receptor; egfr inhibitors; overall survival; progression-free survival; tumour response rate
5.  Swallowing Function Following post Chemoradiotherapy Neck Dissection – Review of Findings and Analysis of Contributing Factors 
Objective
This study assesses swallowing function following chemoradiotherapy and neck dissection in head and neck cancer patients and investigates clinical, treatment and neck dissection factors associated with dysphagia.
Study Design
Case series with chart review
Setting
Tertiary Care Center
Subjects and Methods
88 patients undergoing neck dissection after chemoradiotherapy for advanced head and neck cancer were reviewed. Dysphagia outcome measures included weight loss, diet, gastrostomy tube-dependency and video swallow findings of aspiration or stenosis. Additionally we created a Diet/GT Scale, score 1–5. Univariate and multivariate analysis of clinical, treatment or neck dissection factors potentially associated with dysphagia outcome measures was undertaken.
Results
Peak mean weight loss was 17% at 6 months after chemoradiotherapy. At 12 months a soft/regular diet was taken by 78/88 (89%) and only 1/88 (1%) of patients were nil per os. Gastrostomy tube-dependence at 6, 12, 24 months was 53%, 25%, and 10%. Diet/GT score was 5 (gastrostomy tube removed and soft/regular diet) for 47% at 6 months, 74% at 12 months and 89% at 24 months. Multivariate analyses revealed that higher tumor stage was associated with a lower Diet/GT score at 12 months (p=0.02) and gastrostomy-dependence at 12 (p=0.01) and 24 months (p=0.04).
Conclusion
Despite the addition of neck dissection to chemoradiotherapy, nearly all patients took a soft or regular diet, reached a Diet/GT score of 5 and only 1% remained nil per os. A higher tumor stage is associated with a lower Diet/GT score and gastrostomy tube-dependency beyond 12 months.
doi:10.1177/0194599811403075
PMCID: PMC3434459  PMID: 21493276
6.  Planned neck dissection following chemo-radiotherapy in advanced HNSCC 
Background
Neck dissection has traditionally played an important role in the management of patients with regionally advanced head and neck squamous cell carcinoma (HNSCC) treated with radical radiotherapy alone. However, with the incorporation of chemotherapy in the therapeutic strategy for advanced HNSCC and resultant improvement in outcome the routine use of post chemo-radiotherapy neck dissection is being questioned.
Methods
Published data for this review was identified by systematically searching MEDLINE, CANCERLIT & EMBASE databases from 1995 until date with restriction to the English language.
Results
There is lack of high quality evidence on the role of planned neck dissection in advanced HNSCC treated with chemo-radiotherapy. A systematic literature search could identify only one small randomized controlled trial (Level I evidence) addressing this issue, albeit with major limitations. Upfront neck dissection followed by chemo-radiotherapy resulted in better disease-specific survival as compared to chemoradiation only. Several single arm prospective and retrospective reports were also identified with significant heterogeneity and often-contradictory conclusions.
Conclusions
Planned neck dissection after radical chemo-radiotherapy achieves a high level of regional control, but its ultimate benefit is limited to a small subset of patients only. Unless there are better non-invasive ways to identify residual viable disease, the role of such neck dissection shall remain debatable. A large randomized controlled trial addressing this issue is needed to clarify its role and provide evidence-based answers.
doi:10.1186/1477-7800-1-6
PMCID: PMC520831  PMID: 15377383
chemo-radiotherapy; HNSCC; and neck dissection
7.  SITE OF DISEASE AND TREATMENT PROTOCOL AS CORRELATES OF SWALLOWING FUNCTION IN PATIENTS WITH HEAD AND NECK CANCER TREATED WITH CHEMORADIATION 
Head & neck  2006;28(1):64-73.
Background
The relationship between type of chemoradiation treatment, site of disease, and swallowing function has not been sufficiently examined in patients with head and neck cancer treated primarily with chemoradiation.
Methods
Fifty-three patients with advanced-stage head and neck cancer were evaluated before and 3 months after chemoradiation treatment to define their swallowing disorders and characterize their swallowing physiology by site of lesion and chemoradiation protocol. One hundred forty normal subjects were also studied.
Results
The most common disorders at baseline and 3 months after treatment were reduced tongue base retraction, reduced tongue strength, and slowed or delayed laryngeal vestibule closure. Frequency of functional swallow did not differ significantly across disease sites after treatment, although frequency of disorders was different at various sites of lesion. The effects of the chemotherapy protocols were small.
Conclusions
The site of the lesion affects the frequency of occurrence of specific swallow disorders, whereas chemoradiation protocols have minimal effect on oropharyngeal swallow function.
doi:10.1002/hed.20299
PMCID: PMC1380204  PMID: 16302193
chemoradiation; swallowing disorders; swallowing physiology; head and neck; videofluoroscopy
8.  Hyperfractionated Radiotherapy with Concurrent Cisplatin/5-Fluorouracil for Locoregional Advanced Head and Neck Cancer: Analysis of 105 Consecutive Patients 
Objective. We reviewed a cohort of patients with previously untreated locoregional advanced head and neck squamous cell carcinoma (HNSCC) who received a uniform chemoradiotherapy regimen. Methods. Retrospective review was performed of 105 patients with stage III or IV HNSCC treated at Greater Baltimore Medical Center from 2000 to 2007. Radiation included 125 cGy twice daily for a total 70 Gy to the primary site. Chemotherapy consisted of cisplatin (12 mg/m2/h) daily for five days and 5-fluorouracil (600 mg/m2/20 h) daily for five days, given with weeks one and six of radiation. All but seven patients with N2 or greater disease received planned neck dissection after chemoradiotherapy. Primary outcomes were overall survival (OS), locoregional control (LRC), and disease-free survival (DFS). Results. Median followup of surviving patients was 57.6 months. Five-year OS was 60%, LRC was 68%, and DFS was 56%. Predictors of increased mortality included age ≥55, female gender, hypopharyngeal primary, and T3/T4 stage. Twelve patients developed locoregional recurrences, and 16 patients developed distant metastases. Eighteen second primary malignancies were diagnosed in 17 patients. Conclusions. The CRT regimen resulted in favorable outcomes. However, locoregional and distant recurrences cause significant mortality and highlight the need for more effective therapies to prevent and manage these events.
doi:10.1155/2012/754191
PMCID: PMC3388433  PMID: 22778748
9.  Planned Neck Dissection Following Radiation Treatment for Head and Neck Malignancy 
Introduction. Optimal therapy for patients with metastatic neck disease remains controversial. Neck dissection following radiotherapy has traditionally been used to improve locoregional control. Methods. A retrospective review of 28 patients with node-positive head and neck malignancy treated with planned neck dissection following radiotherapy between January 2002 and December 2005 was performed to assess treatment outcomes. Results. Median interval to neck dissection was 9.6 weeks with a median number of 21 + 9 lymph nodes per specimen. Ten of 31 (32%) neck dissection specimens demonstrated evidence of residual carcinoma. Overall survival at two years was 85%; five-year overall survival was 65%. Concurrent chemotherapy did not impact the presence of residual neck disease. Conclusion. Based on the frequency of residual malignancy in the neck of patients treated with primary radiotherapy, a planned, postradiotherapy neck dissection should be strongly advocated for all patients with advanced-stage neck disease.
doi:10.1155/2012/954203
PMCID: PMC3462392  PMID: 23049562
10.  Metastatic squamous cell carcinoma neck with occult primary: A retrospective analysis 
Introduction:
Metastatic carcinoma in the lymph nodes of the neck from an unknown primary is relatively rare, accounting for about 3% of all head and neck cancers. Management of secondary neck of undetermined primary is controversial.
Materials and Methods:
The case records of all the patients treated in the Department of Radiotherapy, Chatrapati Shahuji Maharaj Medical University, from Oct 1999 to Sep 2004, were studied and the patients with secondary neck without a known primary tumor were analyzed in detail to elucidate the outcome of various treatment modalities in various stages of the disease. One hundred and forty patients were found to be eligible for this analysis. Initial treatment could be divided into two categories: concurrent chemoradiation (n=76) and radiotherapy alone (n=64).
Results:
The patients who had received radiotherapy alone (53.1%) had lesser complete response as compared to those who had received chemoradiotherapy (68.4%). The overall survival duration in patients of the radiotherapy treatment group ranged from 5 to 60 months, with an average (±SD) of 31.06 ± 21.01 months, while in the chemoradiotherapy treatment group it ranged from 6 to 60 months, with an average (±SD) of 39.42 ± 21.33 months. Both hematological and nonhematological toxicities, although higher in the chemoradiotherapy group, showed statistically insignificant differences.
Conclusion:
To the best of our knowledge, this is the only study evaluating the role of concurrent chemoradiation in cases of secondary neck with primary unknown. The improved response rates along with an increased survival (both disease free and overall) show the superiority of chemoradiotherapy in the management of such cases.
doi:10.4103/0971-5851.65334
PMCID: PMC2930299  PMID: 20838553
Chemoradiotherapy; head and neck; metastatic cervical lymph node; radiotherapy; unknown primary
11.  Phase II Trial of Hyperfractionated IMRT and Concurrent Weekly Cisplatin for Stage III and IVa Head and Neck Cancer 
Purpose
Investigate a novel chemoradiation regimen designed to maximize locoregional control (LRC) and minimize toxicity for patients with advanced head and neck squamous cell carcinoma (HNSCC).
Patients and Methods
Patients received hyperfractionated intensity modulated radiation therapy (HIMRT) in 1.25 Gy fractions bid to 70 Gy to high-risk planning target volume (PTV). Intermediate and low-risk PTVs received 60 Gy and 50 Gy, at 1.07 and 0.89 Gy per fraction, respectively. Concurrent cisplatin 33 mg/m2/week was started week 1. Patients completed the Quality of Life Radiation Therapy Instrument prior to (PRE), at end of treatment (EOT), and at 1, 3, 6, 9, and 12 months. Overall survival (OS), progression-free (PFS), LRC, and toxicities were assessed.
Results
Thirty of 39 patients (77%) were alive without disease at median follow-up of 37.5 months. Actuarial 3-year OS, PFS, and LRC were 80%, 82%, and 87%, respectively. No failures occurred in the electively irradiated neck and there were no isolated neck failures. Head and neck QOL was significantly worse in 18 of 35 patients (51%): mean 7.8 PRE versus 3.9 EOT. By month 1, H&N QOL returned near baseline: mean 6.2 (sd=1.7). Most common acute grade 3+ toxicities were mucositis (38%), fatigue (28%), dysphagia (28%) and leukopenia (26%).
Conclusions
Hyperfractionated IMRT with low-dose weekly cisplatin resulted in good LRC with acceptable toxicity and QOL. Lack of elective nodal failures despite very low dose per fraction has led to an attempt to further minimize toxicity by reducing elective nodal doses in our subsequent protocol.
doi:10.1016/j.ijrobp.2009.12.046
PMCID: PMC2902601  PMID: 20378262
Hyperfractionation; IMRT; chemoradiation; head and neck cancer
12.  Current advances in diagnosis and surgical treatment of lymph node metastasis in head and neck cancer 
Still today, the status of the cervical lymph nodes is the most important prognostic factor for head and neck cancer. So the individual treatment concept of the lymphatic drainage depends on the treatment of the primary tumor as well as on the presence or absence of suspect lymph nodes in the imaging diagnosis. Neck dissection may have either a therapeutic objective or a diagnostic one. The selective neck dissection is currently the method of choice for the treatment of patients with advanced head and neck cancers and clinical N0 neck. For oncologic reasons, this procedure is generally recommended with acceptable functional and aesthetic results, especially under the aspect of the mentioned staging procedure. In this review article, current aspects on pre- and posttherapeutic staging of the cervical lymph nodes are described and the indication and the necessary extent of neck dissection for head and neck cancer is discussed. Additionally the critical question is discussed if the lymph node metastasis bears an intrinsic risk of metastatic development and thus its removal in a most possible early stage plays an important role.
doi:10.3205/cto000086
PMCID: PMC3544246  PMID: 23320056
head and neck cancer; lymphogenic metastasis; lymph node metastasis; neck dissection
13.  Use of gel caps to aid endoscopic insertion of nasogastric feeding tubes: a comparative audit 
Head & Neck Oncology  2011;3:24.
Introduction
Nutrition is crucial to successful outcomes in peri-operative head and neck cancer patients. Nasogastric feeding tubes are an accepted and safe method of providing enteral nutrition in the short-term. Many methods have been advocated for successfully inserting and securing nasogastric tubes and each practitioner will have his or her preferred technique.
Objectives
To confirm the effectiveness of using gel caps combined with the flexible nasendoscope for the insertion of nasogastric feeding tubes in head and neck cancer patients following failure of traditional methods.
Participants
Thirty-five consecutive patients requiring nasogastric feeding tubes were included in this comparative audit. All had failed traditional insertion methods after 2 attempts and were therefore eligible for inclusion. Patients were randomised to undergo attempted insertion with the flexible nasendoscope with or without the use of a gel cap (both methods have been previously described).
Audit Outcome
Primary outcome measures showed no significant difference between the two techniques.
Discussion
We found the methodology to be of no greater benefit to our patients when compared to our alternative current practice for failed blind nasogastric tube insertion. We retain this methodology in our armamentarium for difficult circumstances but have continued with our standard practice for most patients needing nasogastric tube placement.
doi:10.1186/1758-3284-3-24
PMCID: PMC3108932  PMID: 21548978
14.  HPV & head and neck cancer: a descriptive update 
Head & Neck Oncology  2009;1:36.
The incidence of head and neck squamous cell carcinoma (HNSCC) has been gradually increasing over the last three decades. Recent data have now attributed a viral aetiology to a subset of head and neck cancers. Several studies indicate that oral human papillomavirus (HPV) infection is likely to be sexually acquired. The dominance of HPV 16 in HPV+ HNSCC is even greater than that seen in cervical carcinoma of total worldwide cases. Strong evidence suggests that HPV+ status is an important prognostic factor associated with a favourable outcome in head and neck cancers.
Approximately 30 to 40% of HNSCC patients with present with early stage I/II disease. These patients are treated with curative intent using single modality treatments either radiation or surgery alone. A non-operative approach is favored for patients in which surgery followed by either radiation alone or radiochemotherapy may lead to severe functional impairment. Cetuximab, a humanized mouse anti-EGFR IgG1 monoclonal antibody, improved locoregional control and overall survival in combination with radiotherapy in locally advanced tumours but at the cost of some increased cardiac morbidity and mortality.
Finally, the improved prognosis and treatment responses to chemotherapy and radiotherapy by HPV+ tumours may suggest that HPV status detection is required to better plan and individualize patient treatment regimes.
doi:10.1186/1758-3284-1-36
PMCID: PMC2770444  PMID: 19828033
15.  Effect of neoadjuvant chemoradiation and postoperative radiotherapy on expression of heat shock protein 70 (HSP70) in head and neck vessels 
Background
Preoperative radiotherapy and chemotherapy in patients with head and neck cancer result in changes to the vessels that are used to construct microsurgical anastomoses. The aim of the study was to investigate quantitative changes and HSP70 expression of irradiated neck recipient vessels and transplant vessels used for microsurgical anastomoses.
Methods
Of 20 patients included in this study five patients received neoadjuvant chemoradiation, another five received conventional radiotherapy and 10 patients where treated without previous radiotherapy. During surgical procedure, vessel specimens where obtained by the surgeon. Immunhistochemical staining of HSP70 was performed and quantitative measurement and evaluation of HSP70 was carried out.
Results
Conventional radiation and neoadjuvant chemoradiation revealed in a thickening of the intima layer of recipient vessels. A increased expression of HSP70 could be detected in the media layer of the recipient veins as well as in the transplant veins of patients treated with neoadjuvant chemoradiation. Radiation and chemoradiation decreased the HSP70 expression of the intima layer in recipient arteries. Conventional radiation led to a decrease of HSP70 expression in the media layer of recipient arteries.
Conclusion
Our results showed that anticancer drugs can lead to a thickening of the intima layer of transplant and recipient veins and also increase the HSP70 expression in the media layer of the recipient vessels. In contrast, conventional radiation decreased the HSP70 expression in the intima layer of arteries and the media layer of recipient arteries and veins. Comparing these results with wall thickness, it was concluded, that high levels of HSP70 may prevent the intima layer of arteries and the media layer of vein from thickening.
doi:10.1186/1748-717X-6-81
PMCID: PMC3146838  PMID: 21745403
16.  Prophylactic PEG placement in head and neck cancer: How many feeding tubes are unused (and unnecessary)? 
AIM: To determine the rate of use and non-use of prophylactic percutaneous endoscopic gastrostomy (PEG) tubes among patients with head and neck cancer (HNC) patients.
METHODS: All patients with HNC undergoing PEG between January 1, 2004 and June 30, 2006 were identified. Patients (or their next-of-kin) were surveyed by phone and all available medical records and cancer registry data were reviewed. Prophylactic PEG was defined as placement in the absence of dysphagia and prior to radiation or chemoradiation. Each patient with a prophylactic PEG was assessed for cancer diagnosis, type of therapy, PEG use, and complications related to PEG.
RESULTS: One hundred and three patients had PEG tubes placed for HNC. Thirty four patients (33%) could not be contacted for follow-up. Of the 23 (22.3%) patients with prophylactic PEG tubes, 11/23 (47.8%) either never used the PEG or used it for less than 2 wk. No association with PEG use vs non-use was observed for cancer diagnosis, stage, or specific cancer treatment. Non-use or limited use was observed in 3/6 (50%) treated with radiation alone vs 8/17 (47.1%) treated with chemoradiation (P = 1.0), and 3 of 10 (30%) treated with surgery vs 8 of 13 (62%) not treated with surgery (P = 0.21). Minor complications were reported in 5/23 (21.7%). One (4.3%) major complication was reported.
CONCLUSION: There is a high rate of unnecessary PEG placement when done prophylactically in patients with head and neck cancer.
doi:10.3748/wjg.v17.i8.1004
PMCID: PMC3057142  PMID: 21448351
Head and neck cancer; Percutaneous gastrostomy tube; Prophylactic
17.  Anatomic sites at elevated risk of second primary cancer after an index head and neck cancer 
Cancer causes & control : CCC  2011;22(5):671-679.
Background
Patients with head and neck squamous cell carcinoma (HNSCC) are at significantly elevated risk of second primary malignancies (SPM), most commonly within the head and neck, lung, and esophagus (HNLE). Our objectives were to quantify the excess risk of SPM across all anatomic sites in which SPM risk is meaningfully elevated, including non-HNLE sites, in a large cohort of US patients.
Methods
Population-based analysis of 75,087 patients with HNSCC in the SEER program, quantifying excess SPM risk by integrating relative (standardized incidence ratio; SIR) and absolute (excess absolute risk per 10,000 person-years at risk; EAR) statistics.
Results
In HNSCC patients, the SIR of a second primary solid cancer was 2.2 (95% CI 2.1–2.2), corresponding to EAR of 167.7 additional cases per 10,000 person-years at risk. Over 1 year, 60 patients would need to be followed to observe one excess SPM. Lung cancer burden was most markedly elevated in absolute terms (EAR = 75.2), followed by HN (EAR = 59.8), esophageal (EAR = 14.2), and colorectal (EAR = 4.3) cancers. Lesser but significant excess risks were also observed for cancers of the bladder, liver, stomach, pancreas, kidney, salivary glands, nasopharynx, uterine cervix, and lymphoma.
Conclusions
Data from a large population-based US cohort reveals that HNSCC patients experience markedly excess risk of SPM, predominantly in the HNLE sites. Furthermore, the risk of SPM is also meaningfully elevated, although to a lesser degree, in multiple other tobacco-associated sites.
doi:10.1007/s10552-011-9739-2
PMCID: PMC3085084  PMID: 21327458
Second primary; Malignancy; Cancer; Head and neck; Lung; Esophagus; Colon
18.  Advanced Maxillary Sinus Cancer Treated with Concurrent Chemoradiotherapy with Intra-Arterial Cisplatin/Docetaxel and Oral S-1: Own Experience and Literature Review 
Case Reports in Oncology  2011;4(3):492-498.
Intra-arterial (IA) chemotherapy for head and neck cancer is effective and multiple IA concurrent chemoradiation (CCRT) protocols have been reported. However, the role of IA CCRT in the multimodality treatment of head and neck cancer is still controversial. We have treated 5 cases of unresectable T4 maxillary sinus squamous cell carcinoma with IA cisplatin (CDDP) and docetaxel (DOC) and CCRT with oral S-1. We report our experience and the effectiveness and feasibility of this combination as an alternative choice of treatment for inoperable head and neck cancer. The patients received an IA infusion of CDDP (50–70 mg/m2) and DOC (50–60 mg/m2) through the femoral artery, followed by CCRT with oral S-1. The IA infusion was repeated up to 3 times and the radiation was dosed at up to 60–70 Gy. Complete response was achieved in 4 patients and partial response in one, giving an overall response rate of 100%. The most common grade 3 or 4 toxicities were anorexia (80%), mucositis (80%) and leukopenia (80%), all of which were manageable. CCRT with IA CDDP/DOC and oral S-1 was effective and tolerated. Although preliminary, the response rate encourages further pursuit and definitive evaluation of this combination for the treatment of inoperable advanced head and neck cancer.
doi:10.1159/000332759
PMCID: PMC3220904  PMID: 22114575
Head and neck cancer; Intra-arterial chemoradiotherapy; Cisplatin; Docetaxel; S-1
19.  Axillary nodal metastasis at primary presentation of an oropharyngeal primary carcinoma: a case report and review of the literature 
Introduction
Axillary nodal metastasis is very rare in head and neck squamous cell carcinoma. The few cases reported in the literature all involve patients who have previously undergone either neck dissection alone, or neck dissection and radiotherapy to the neck, and subsequently develop delayed recurrences of disease, with axillary nodal involvement.
Case presentation
We present the case of a 62-year-old man of Cape Malay ethnicity, who presented with an oropharyngeal squamous cell carcinoma, and cervical and axillary nodal metastasis at primary presentation.
Conclusion
Whilst previous reports in the literature suggest routine examination of the axilla is advisable in patients with previously treated neck cancer and recurrence of head and neck cancer, we propose that the axilla should be routinely examined in new cases, particularly when there is involvement of the level 5 nodes.
doi:10.4076/1752-1947-3-7230
PMCID: PMC2737770  PMID: 19830142
20.  How common is hypothyroidism after external radiotherapy to neck in head and neck cancer patients? 
Purpose:
To identify the occurrence of clinical and subclinical hypothyroidism among head and neck cancer patients receiving radiation to the neck and to justify routine performing of thyroid function tests during follow-up.
Materials and Methods:
This is a prospective nonrandomized study of 45 patients of head and neck cancer, receiving radiotherapy (RT). Thyroid stimulating hormone and T4 estimations were done at baseline and at 4 months and 9 months following RT.
Results:
Of the 45 patients, 37(82.2 %) were males and eight (17.8 %) were females. All patients received radiation to the neck to a dose of >40Gy. 35.6% received concurrent chemotherapy. Two patients underwent prior neck dissection. Fourteen patients (31.1%) were found to have clinical hypothyroidism (P value of 0.01). Five (11.1%) patients were found to have subclinical hypothyroidism with a total 19 of 45 (42.2%) patients developing radiation-induced hypothyroidism. Nine of 14 patients with clinical hypothyroidism were in the age group of 51 to 60 years (P=0.0522). Five of 16 patients who received chemoradiation and nine of 29 who received RT alone developed clinical hypothyroidism. Above 40 Gy radiation dose was not a relevant risk factor for hypothyroidism.
Conclusion:
Hypothyroidism (clinical or subclinical) is an under-recognized morbidity of external radiation to the neck which is seen following a minimum dose of 40 Gy to neck. Recognizing hypothyroidism (clinical or subclinical) early and treating it prevents associated complications. Hence, thyroid function tests should be made routine during follow-up.
doi:10.4103/0971-5851.92813
PMCID: PMC3342720  PMID: 22557780
Head and neck cancer; hypothyroidism; radiotherapy; subclinical hypothyroidism
21.  Outcomes after Surgical Resection of Head and Neck Paragangliomas: A Review of 61 Patients 
Skull Base  2011;21(3):171-176.
We reviewed the postoperative functional outcome following surgical resection of paragangliomas in patients with and without preoperative cranial nerve dysfunction. Patients who underwent surgical resections of head and neck paragangliomas were reviewed with functional outcomes defined as feeding tube and/or tracheostomy dependence, need for vocal cord medialization, and incidence of cerebral vascular accidents as primary end points. Secondary end points included pre- and postoperative function of lower cranial nerves and the impact of this dysfunction on long-term functional status. Sixty-one patients were identified: 27 with carotid paraganglioma (CP), 21 with jugular paraganglioma (JP), 8 with tympanic paragangliomas, 4 with vagal paragangliomas (VPs), and 1 with aortopulmonary paraganglioma. Following resection, 8 patients were feeding tube dependent, 14 patients required vocal cord medialization, 2 patients suffered strokes, but no patients required tracheostomy tubes. Twenty percent of patients (4/20) with JP and postoperative cranial neuropathies were feeding tube dependent, and 80% of patients (4/5) with CP and postoperative cranial nerve dysfunction were feeding tube dependent. Cranial nerve deficits were more common in patients with JP relative to those with CP. However, when cranial nerve dysfunction was present, our patients with CP had a higher incidence of temporary feeding tube dependence. Overall, 98% of patients were able to resume oral nutrition.
doi:10.1055/s-0031-1275251
PMCID: PMC3312103  PMID: 22451821
Paragangliomas; functional outcomes; feeding tube dependence; cranial nerve dysfunction
22.  Head and neck cancer in elderly patients: is microsurgical free-tissue transfer a safe procedure? 
SUMMARY
The safety and success of microvascular transfer have been well documented in the general population, but the good results achieved with the use of free flaps in elderly patients have received little attention. This study sought to identify differences in complications, morbidity and functional outcomes between elderly (≥ 75 years) and younger (< 75 years) patients treated surgically for advanced head and neck cancer using the Head and Neck 35 module of the European Organisation for Research and Treatment of Cancer quality of life questionnaire. Patient treatment consisted of composite resection, including excision of the primary tumour with ipsilateral or bilateral neck dissection and microvascular reconstruction. Eighty-five microvascular tissue transfers were performed to reconstruct major surgical defects. Postoperative radiation therapy was performed when indicated. Total flap loss occurred in three cases in elderly patients and two cases in younger patients. The rates of major surgical complication were 9% in young patients and 11% in elderly patients. No significant difference was observed between the two groups in the rates of major and minor flap complications, morbidity or long-term functional outcome. The results of the present analysis indicate that free-flap microvascular reconstruction can be considered a safe procedure in elderly patients with head and neck cancer.
PMCID: PMC3552542  PMID: 23349555
Head and neck cancer; Elderly patient; Microvascular free flap; Complication; Functional outcome
23.  Radiotherapy for the management of locally advanced squamous cell carcinoma of the head and neck 
Oral diseases  2008;15(2):121-132.
Background
Squamous cell carcinomas of the head and neck (SCCHN) affect approximately 35,000 people in the United States yearly. Although survival has improved with advances in therapy, patients with advanced stages of SCCHN continue to have a poor prognosis. An understanding of rationale for treatment selection, newer developments in therapy, and treatment toxicity is critical.
Methods
Standard methods of treating locally advanced SCCHN are reviewed. Advances in medical and radiotherapeutic management are discussed and the toxicities of therapy are described.
Results
Post-operative chemoradiation is used in patients with high risk characteristics. Induction chemotherapy and altered fractionation radiation treatment have been evaluated as alternatives to definitive chemo-radiotherapy. Targeted agents such as cetuximab may prove to increase survival with minimal increase in toxicity profile. Technological improvements such as the use of intensity modulated radiation treatment (IMRT) have proven to decrease some debilitating side effects from radiation treatment.
Conclusions
Locally advanced SCCHN continues to present a therapeutic challenge. Survival, local control, and quality of life are all goals of treatment. The optimal method of treating locally advanced SCCHN is the subject of ongoing research. Long term side effects can be minimized with the use of newer technologies and with careful treatment planning.
doi:10.1111/j.1601-0825.2008.01495.x
PMCID: PMC2640438  PMID: 19036056
head and neck cancer; radiation treatment; chemotherapy
24.  Late development of esophageal stricture following radiation and chemotherapy for small cell carcinoma of the lung: A case report 
Cases Journal  2008;1:169.
Background
The development of esophageal stricture is not an uncommon side effect of radiation and chemotherapy for neck and thoracic malignancies. Depending on the study, it may occur anywhere from 2–3 weeks to 4–8 months after therapy. However, chronic late presentations of post-treatment stricture are highly atypical events.
Case Presentation
The authors describe herein an unusual case of a 65 year old male with esophageal stricture presenting as dysphagia and complicated by multiple episodes of aspiration pneumonia four years after chemoradiation treatment for small cell carcinoma of the lung. The patient's symptoms were ameliorated after esophageal dilation with stenting.
Conclusion
Latent esophageal stricture should be suspected in any patient previously treated with radiation and chemotherapy regardless of how long ago the therapy was initiated.
doi:10.1186/1757-1626-1-169
PMCID: PMC2556315  PMID: 18803839
25.  Novel Susceptibility Loci for Second Primary Tumors/Recurrence in Head and Neck Cancer Patients: Large Scale Evaluation of Genetic Variants 
Background
This study was aimed to identify novel susceptibility variants for second primary tumor (SPT) or recurrence in curatively treated early stage head and neck squamous cell carcinoma (HNSCC) patients.
Methods
We constructed a custom chip containing a comprehensive panel of 9645 chromosomal and mitochondrial single nucleotide polymorphisms (SNPs) representing 998 cancer-related genes selected by a systematic prioritization schema. Using this chip, we genotyped 150 early-stage HNSCC patients with and 300 matched patients without SPT/recurrence from a prospectively conducted randomized trial and assessed the association of these SNPs with risk of SPT/recurrence.
Results
Individually, six chromosomal SNPs and seven mitochondrial SNPs (mtSNPs) were significantly associated with risk of SPT/recurrence after adjustment for multiple comparisons. A strong gene-dosage effect was observed these SNPs were combined, as evidenced by a progressively increasing SPT/recurrence risk as the number of unfavorable genotypes increased (P for trend < 1.00×10−20). Several polygenic analyses suggest an important role of interconnected functional network and gene-gene interaction in modulating SPT/recurrence. Furthermore, incorporation of these genetic markers into a multivariate model improved significantly the discriminatory ability over the models containing only clinical and epidemiologic variables.
Conclusions
This is the first large scale systematic evaluation of germline genetic variants for their roles in HNSCC SPT/recurrence. The study identified several promising susceptibility loci and demonstrated the cumulative effect of multiple risk loci in HNSCC SPT/recurrence. Furthermore, this study underscores the importance of incorporating germline genetic variation data with clinical and risk factor data in constructing prediction models for clinical outcomes.
doi:10.1158/1940-6207.CAPR-09-0025
PMCID: PMC2964280  PMID: 19584075
iSelect Infinium; Single nucleotide polymorphisms; Head and neck cancer; Secondary primary tumor; recurrence

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