SUMMARY

Patients with head and neck squamous cell carcinoma (HNSCC) often require assistance from family caregivers during the treatment and post-treatment period. This review article sought to summarize current findings regarding the psychological health of HNSCC caregivers, including factors that may be associated with poorer psychological health. Online databases (PUBMED, MEDLINE and PSYCINFO) were searched for papers published in English through September 2010 reporting on the psychological health of caregivers of HNSCC patients. Eleven papers were identified. Caregivers experience poorer psychological health, including higher levels of anxious symptoms, compared to patients and to the general population. Fear of patient cancer recurrence is evident among caregivers and is associated with poorer psychological health outcomes. The 6-month interval following diagnosis is a significant time of stress for caregivers. Greater perceived social support may yield positive benefits for the psychological health of caregivers. To date, there have been relatively few reports on the psychological health of caregivers of HNSCC patients. Well designed, prospective, longitudinal studies are needed to enhance our understanding of how caregiver psychological health may vary over the cancer trajectory and to identify strategies for improving caregiver outcomes.

Background

The impact of post-treatment neck dissection on prolonged feeding tube dependence in head and neck squamous cell cancer (HNSCC) patients treated with primary radiation or chemoradiation remains unknown.

Methods

Retrospective cohort study using propensity score adjustment to investigate the effect of neck dissection on prolonged feeding tube dependence.

Results

A review of 67 patients with node positive HNSCC (T1-4N1-3), treated with primary radiation or chemoradiation, with no evidence of tumor recurrence and follow-up of at least 24 months was performed. Following adjustment for covariates, the relative risk of feeding tube dependence at 18 months was significantly increased in patients treated with post-treatment neck dissection (RR 4.74, 95% CI 2.07-10.89). At 24 months, the relative risk of feeding tube dependence in the patients having undergone neck dissection increased further (RR 7.66, 95% CI 2.07-10.89). Of patients with feeding tubes two years after completing treatment, 75% remained feeding tube dependent.

Conclusion

Neck dissection may contribute to chronic oropharyngeal dysphagia in HNSCC patients treated with primary radiation or chemoradiation.

Purpose

Appropriate treatment of the lower neck when using IMRT is controversial. Our study tried to determine differences in clinical outcomes using IMRT or a standard LNF to treat low neck.

Methods and Materials

This is a retrospective, single institution study. Ninety-one patients with squamous cell carcinoma of head and neck cancer were treated with curative intent. Based on physician preference, some patients were treated with LNF (PTV3) field using a single anterior photon field matched to the IMRT field. Field junctions were not feathered. The endpoints were time to failure and use of PEG tube (as a surrogate of laryngeal edema causing aspiration) and analysis done with chi-square and the log-rank tests.

Results

Median follow up 21 months (range 2 – 89). The median age 60 years. Thirty seven (41%) were treated with LNF, 84% were stage III or IV. PEG tube was required in 30% as opposed to 33% without the use of LNF. N2 or 3 neck disease was treated more commonly without a LNF (38% vs. 24%, p = 0.009). Failures occurred in 12 patients (13%). Only one patient treated with LNF failed regionally, 4.5 cm above the match line. The 3-year disease-free survival rate was 87%, 79% with LNF and without LNF respectively (p = 0.2) and the 3-year LR failure rate was 4%, 21% respectively, (p = 0.04).

Conclusions

Using LNF to treat the low neck did not increase the risk of regional failure “in early T& early N diseases” or decrease PEG tube requirements.

Purpose

The validity of sentinel lymph node biopsy (SLNB) for T1 or T2, clinically N0, oral cancer was tested by correlation of sentinel node pathologic status with that of nodes within the completion neck dissection.

Methods

This prospective, cooperative group trial involved 25 institutions over a 3-year period. One hundred forty patients with invasive oral cancers, stage T1 and T2, N0 including 95 cancers of the tongue, 26 of the floor of mouth, and 19 other oral cancers were studied. The study excluded lesions with diameter smaller than 6 mm or minimal invasion. Imaging was used to exclude nonpalpable gross nodal disease. Patients underwent injection of the lesion with 99mTc-sulfur colloid, nuclear imaging, narrow-exposure SLNB, and completion selective neck dissection. The major end point was the negative-predictive value (NPV) of SLNB.

Results

In the 106 SLNBs, which were found to be pathologically and clinically node-negative by routine hematoxylin and eosin stain, 100 patients were found to have no other pathologically positive nodes, corresponding to a NPV of 94%. With additional sectioning and immunohistochemistry, NPV was improved to 96%. In the forty patients with proven cervical metastases, the true-positive rate was 90.2% and was superior for tongue tumors relative to floor of mouth. For T1 lesions, metastases were correctly identified in 100%.

Conclusion

For T1 or T2 N0 oral squamous cell carcinoma, SLNB with step sectioning and immunohistochemistry, performed by surgeons of mixed experience levels, correctly predicted a pathologically negative neck in 96% of patients (NPV, 96%).

Purpose

Detect tumor-related DNA using LigAmp in histologically clear margins and associate results with clinical outcome.

Experimental Design

Patients with head and neck cancer were registered for molecular analysis of surgical margins. Adequacy of resection was ensured using histologic margin analysis. Further margins were then harvested and DNA extracted. TP53 mutations in tumor were determined using Affymetrix p53 GeneChip. Margins were analyzed by Ligamp in comparison with standard curves for quantification of mutant DNA. Ligation employed 2 oligonucleotides to isolate DNA targeting the mutation. Ligated DNA was amplified using real-time PCR. The quantity of mutation in the margin was determined as percent of mutant species relative to plasmid (MRP) and relative to tumor (MRT). Cutpoints were identified and defined groups evaluated for local failure-free, cancer-specific, and overall survival. Study margins were examined for presence of tumor by light microscopy.

Results

Tissue from 95 patients with common mutations was analyzed. Fifteen experienced local recurrence. Cutpoints of 0.15% for MRP and 0.5% for MRT were chosen as most selective of recurrent cases. LigAmp had slightly better area under the ROC curve (p=0.09) than light microscopy correctly predicting 9 of 15 recurrent tumors. There were 6 false negative cases and 26 false positive results. No statistically significant distinctions were observed in cancer-specific or overall survival in this limited cohort.

Conclusions

Ligamp provides quantifiable, sensitive detection of mutant DNA in histologically normal margins. Detection of mutant species in margins may identify patients at risk of local recurrence.

Purpose

We sought to improve outcomes for patients with high-risk head and neck squamous cell cancer (HNSCC) after surgical resection by testing the feasibility and safety of early postoperative chemotherapy followed by concurrent chemoradiotherapy.

Patients and Methods

Eligible patients had resected, stages III to IV HNSCC with positive margins, extracapsular nodal extension, or multiple positive nodes. Paclitaxel (80 mg/m2) was given once weekly during postoperative weeks 2, 3, and 4 and was given before radiation therapy (RT). Paclitaxel (30 mg/m2) and cisplatin (20 mg/m2) were given once weekly during the last 3 weeks of RT (60 Gy over 6 weeks, beginning 4 to 5 weeks after surgery). The primary end points were treatment safety and tolerability compared with concurrent cisplatin (100 mg/m2 every 3 weeks) and RT, as tested in Radiation Therapy Oncology Group trial RTOG 9501.

Results

The median follow-up time for the 70 patients enrolled was 3.3 years (range, 0.6 to 4.4 years) for surviving patients. Tolerability of all treatment components was comparable to that of RTOG 9501 treatment, which is the current standard of care (compliance rate, 75%; 95% CI, 63% to 85%). One patient died, and seven patients experienced grade 4 nonhematologic toxicities. Rates of locoregional control, disease-free survival, and overall survival exceeded those of RTOG 9501 after adjustment for important prognostic variables (ie, positive margins, extracapsular extension, primary site, and performance status).

Conclusion

Chemotherapy soon after surgery followed by concurrent chemoradiotherapy therapy was feasible; tolerance was in line with standard postoperative chemoradiotherapy; and this regimen led to excellent rates of locoregional control and disease-free survival.

Objectives

To compare the results of clinical and pathological staging for a large cohort of patients with head and neck squamous cell carcinoma (HNSCC) and to examine patterns and ramifications of the disparity between staging methods.

Design

Prospective inception cohort (median follow-up, 7 years).

Setting

Multi-institutional cooperative group study (Eastern Cooperative Oncology Group 4393/Radiation Therapy Oncology Group 9614) involving 17 academic medical centers.

Patients

A total of 560 patients with new-onset or recurrent HNSCC enrolled during a 7-year period.

Interventions

Surgical resection with curative intent with or without adjuvant or previous radiotherapy or chemotherapy.

Main Outcome Measures

Clinical staging and pathological staging and the component TN tumor categories were compared with overall and disease-specific survival. Association of survival with staging was derived by means of the proportional hazards model.

Results

Of the 501 cases in which both clinical and pathological staging was available, a disparity was found between at least 1 component tumor category assigned by the 2 methods in almost 50% of cases. Both methods showed a strong association of stage with overall survival for the cohort at large. However, pathological nodal category was a superior predictor (P<.001 vs P=.005), whereas there was an advantage to pathological tumor category in predicting disease-specific survival (P=.01).

Conclusions

Both staging methods are useful in predicting survival, whereas information gained at neck dissection regarding nodal metastases provides some refinement in prognostic results. These findings demonstrate the need for enhanced methods of tumor assessment and apparent benefit of data gathered at neck dissection for accurate disease assessment and stratification.

Given high rates of smoking among cancer patients, smoking cessation treatment is crucial, yet limited data exist to guide integration of such trials into the oncologic context. To determine the feasibility of conducting smoking cessation clinical trials with cancer patients, screening and baseline data from a large randomized placebo-controlled pharmacotherapy trial were analyzed. Descriptive statistics and regression analyses were used to compare enrollees to decliners, describe program enrollees, and assess correlates of confidence in quitting smoking. Of 14,514 screened patients, 263 (<2%) were eligible; 43 (16%) refused enrollment. Among eligible patients, 220 (84%) enrolled. Enrollment barriers included: smoking rate, medical history/contraindicated medication, lack of interest, and language. Compared to enrollees, decliners were more likely to have advanced cancer. The trial enrolled a sample of 67 (>30%) African Americans; participants had extensive smoking histories; many were highly nicotine dependent; and participants consumed about 7 alcoholic beverages/week on average. Head and neck and breast cancer were the most common tumors. Fifty-two (25%) reported depressive symptoms. A higher level of confidence to quit smoking was related to lower depression and lower tumor stage. Integrating a smoking cessation clinical trial into the oncologic setting is challenging, yet feasible. Recruitment strategies are needed for patients with advanced disease and specific cancers. Once enrolled, addressing participant’s depressive symptoms is critical for promoting cessation.

BACKGROUND

The abrogation of function of the tumor-suppressor protein p53 as a result of mutation of its gene, TP53, is one of the most common genetic alterations in cancer cells. We evaluated TP53 mutations and survival in patients with squamous-cell carcinoma of the head and neck.

METHODS

A total of 560 patients with squamous-cell carcinoma of the head and neck who were treated surgically with curative intent were enrolled in our prospective multicenter, 7-year study. TP53 mutations were analyzed in DNA from the tumor specimens with the use of the Affymetrix p53 chip and the Surveyor DNA endonuclease and denaturing high-performance liquid chromatography. Mutations were classified into two groups, disruptive and nondisruptive, according to the degree of disturbance of protein structure predicted from the crystal structure of the p53–DNA complexes. TP53 mutational status was compared with clinical outcome.

RESULTS

TP53 mutations were found in tumors from 224 of 420 patients (53.3%). As compared with wild-type TP53, the presence of any TP53 mutation was associated with decreased overall survival (hazard ratio for death, 1.4; 95% confidence interval [CI], 1.1 to 1.8; P = 0.009), with an even stronger association with disruptive mutations (hazard ratio, 1.7; 95% CI, 1.3 to 2.4; P<0.001) and no significant association with nondisruptive mutations (hazard ratio, 1.2; 95% CI, 0.9 to 1.7; P = 0.16). In multivariate analyses a disruptive TP53 alteration, as compared with the absence of a TP53 mutation, had an independent, significant association with decreased survival (hazard ratio, 1.7; 95% CI, 1.2 to 2.4; P = 0.003).

CONCLUSIONS

Disruptive TP53 mutations in tumor DNA are associated with reduced survival after surgical treatment of squamous-cell carcinoma of the head and neck.