Two studies presented at the 2014 Multidisciplinary Head and Neck Cancer Symposium suggested that positive HPV status could be used as a biomarker indicator related to improved survival.
By evaluating next-generation sequencing data and associated clinical records of head and neck squamous cell carcinoma patients from several institutions, made available through The Cancer Genome Atlas, researchers found that combining Mutant-Allele Tumor Heterogeneity as a biomarker with the patient’s HPV status provided an effective indicator of improved patient outcome.
The TCGA data available for HNSCC patients included 302 patients, with 35 HPV-positive patients. The researchers’ examination confirmed that high tumor MATH at time of surgery is an indicator of poor outcome (high-MATH HR=2.1; 95% CI, 1.4 to 3.2; p = 0.0002, logrank test) and that HPV-positive HNSCC patients have lower average MATH values than HPV-negative HNSCC patients.
In bivariate analysis, both MATH and HPV were significantly associated with survival. When stratified by HPV status, MATH was similarly related to outcome in clinically defined subsets of patients regardless of clinical characteristics such as tumor margins, nodal classification, or tumor staging. Median follow-up with the 173 surviving patients was 22 months.
Genetic heterogeneity of each tumor was assessed by MATH, the percentage ratio of the width to the center of the distribution of tumor-specific mutant-allele fractions. In order to compare to previous studies, analysis was limited to mutant-allele fractions no less than 0.075, and the high-MATH cutoff value of 32, previously found to distinguish outcome classes, was used. Cox proportional hazards analysis was used to evaluate the relations of MATH and HPV to overall survival.
In a separate retrospective analysis of two RTOG studies, researchers found that HPV-positive oropharyngeal patients had a higher overall survival rate than HPV-negative patients.
The study used a retrospective analysis of patients with recurrence of disease after primary therapy in RTOG studies 0129 or 0522, and found that at two years post-treatment, HPV-positive patients had an overall survival rate of 54.6 percent, compared to 27.6 percent in HPV-negative patients.
The analysis included 181 patients with stage III-IV oropharyngeal squamous cell carcinoma with known HPV status (positive = 105; negative = 76), and cancer progression that was local, regional and/or distant after completion of primary cisplatin-based chemotherapy and radiation therapy (standard vs. accelerated fractionation) in RTOG 0129 or cisplatin-AFX with or without cetuximab in RTOG 0522. Tumor status was determined by p16 immunohistochemistry.
Median time to progression was virtually the same for HPV-positive and HPV-negative patients (8.2 months vs. 7.3 months, respectively). Increased risk of death in univariate analysis was associated with high tumor stage at diagnosis (T4 vs. T2-T3), fewer on-protocol cisplatin cycles (=1 vs. 2-3) and distant vs. local/regional recurrent (for all, hazard ratios (HRs) >2.0 and p<0.05).
Risk of death after disease progression increased by 1 percent per cigarette pack-year at diagnosis. Rates were estimated by Kaplan-Meier method and compared by log-rank. HRs were estimated by Cox proportional hazards models and stratified by treatment protocol.
In addition, HPV-positive and HPV-negative patients who underwent surgery after cancer recurrence also experienced improved OS compared to those who did not undergo surgery. Recurrence is most commonly in the lungs for both groups of patients.
Lateral Radiation Therapy Results in Regional Control In Advanced Tonsil Cancer
Limiting radiation therapy to lymph nodes on one side of the neck for advanced tonsil cancer resulted in good local regional control and no cancer recurrence on the untreated side, according to a study.
Additionally, the study results indicate that primary tumor location, rather than the amount of lymph node involvement on the tumor side of the neck, dictates the risk for disease in the opposite side of the neck.
The study, presented at the 2014 Multidisciplinary Head and Neck Cancer Symposium, focused on 46 out of 153 total patients with squamous cell carcinoma of the tonsil who received treatment between 1997 and 2012 at Washington University in St. Louis.
Tumor location was well-documented in the 46 patients who received unilateral radiation therapy, with 40 patients (87 percent) having lateralized primary tumors; two patients (4 percent) had non-lateralized tumors, and in four patients (9 percent), lateralization could not be determined retrospectively.
The patients underwent surgical resection and postoperative intensity modulated radiation therapy, with 30 patients also receiving concurrent chemotherapy.
Of the subset of 46 patients treated unilaterally, 72 percent were men, and the average patient age was 59. Sixty-one percent of patients were current or former smokers, and 33 patients were p16 immunohistochemistry positive (72 percent).
The median follow-up period was 2.8 years. There were no local or regional recurrences reported. Distant metastasis developed in four of the patients (9 percent). Two patients developed second primary cancers.
Daily Humidification Improves Quality-of-Life in Phase III Trial
A phase III trial found that patients who received daily humidification of the mouth and throat region from day one of radiation therapy treatment spent nearly 50 percent fewer days in the hospital to manage their side effects.
The study, presented at the 2014 Multidisciplinary Head and Neck Cancer Symposium, was conducted by the Trans-Tasman Radiation Oncology Group and evaluated 210 head and neck cancer patients in New Zealand and Australia from June 2007 through June 2011.
Patients were randomized to institutional standard of care or humidification using the Fisher & Paykel Healthcare MR880 humidifier. The humidified air is delivered through the nose via a plastic mask that can be worn by patients while sleeping or while sitting.
Patients began humidification on day one of radiation therapy and continued until the ulceration their mouth and throat had resolved. On average, humidification patients spent 57 percent as many days in the hospital to manage side effects (control = 4.1 days vs. humidification = 2.3 days). The return of eating patterns to close to normal was also significantly higher at three months after radiotherapy in the group using humidifiers.
Only 43 patients (42 percent of the patients in the humidification arm) met the defined benchmark of humidification compliance and were able to contribute to the per protocol analysis. The mean average use of humidification for these patients was 3.6 hours per day.
In patients who met the compliance benchmark, the area under the curve for Common Terminology Criteria Adverse Events version 3.0 functional mucositis score was reduced (control = 8.63 vs. humidification PP = 6.74). The proportion of compliant humidification patients who never required a feeding tube was also increased (control = 0.73 vs. humidification PP = 0.85).
There was also a trend for patients to report a reduction in symptom burden when using humidification but only in those patients compliant in using the humidifier.
