Quality-Adjusted Life Years and Disability-Adjusted Life Years Are Better With Concurrent Chemoradiation Therapy Than Induction Chemotherapy Followed by Chemoradiation Therapy in Nasopharyngeal Carcinoma.

Introduction As traditional measures such as overall survival (OS) or disease-free survival (DFS) alone do not give a holistic view of the outcomes of a treatment paradigm, we determine to add the evidence of quality-adjusted life year (QALY) and disability-adjusted life year (DALY) to the outcomes of the nasopharyngeal carcinoma patients (NCP) treated with definitive chemoradiation therapy (chemoRT) with or without induction chemotherapy (induction chemo). Methods This is a retrospective analysis of 85 NCPs treated at an academic state institution. The OS estimated by the Kaplan-Meier method and the multivariate Cox regression model determined the co-variables associated with the OS. The relationship between QALYs gained and DALYs saved were calculated from age of the disease onset, duration of the disease, quality of life (QoL) and disability weights. Results Of the 85 eligible NCPs of this cohort, the disease frequency distribution per the World Health Organization (WHO) classification was 41.2% for Type-I, 42.4% for Type-II, and 16.5% for Type-III. The median follow-up (24 months). The five-year OS of patients treated with concurrent chemoRT vs. induction chemo followed by concurrent chemoRT was 54.7 vs. 14.8% for WHO Type I, 60.1 vs. 58.3% for WHO Type II, and 83.3 vs. 50.0% for WHO Type III (p=0.029). The average DALYs saved with concurrent chemoRT were 12.2 years vs. 5 years for induction chemo followed by concurrent chemoRT. The average QALYs gained with concurrent chemoRT were 6.9 years vs. 3.1 years for induction chemo followed by concurrent chemoRT. Conclusion Patients treated with concurrent chemoRT had an increased QoL when compared to induction chemo followed by concurrent chemoRT. The average DALYs saved were higher in the patients treated with concurrent chemoRT than treated with induction chemo followed by concurrent chemoRT.

Outcomes utilizing intensity-modulated radiotherapy in oropharyngeal cancers: Tonsils versus base of tongue.

BACKGROUND: The purpose of this study was to present the outcomes of oropharyngeal cancers treated with intensity-modulated radiotherapy (IMRT) especially the differences between tonsillar and base of tongue (BOT) primaries. METHODS: Retrospective analysis of 124 patients with biopsy proven squamous cell carcinomas of the oropharynx, treated with IMRT. RESULTS: Human papillomavirus (HPV) association correlated with improvement in survivals in both tonsillar and BOT primaries. At the 2-year median follow-up, the cumulative incidences of locoregional recurrences were 8% in both the tonsil and BOT groups (P = .76) but the distant metastases were 8% in the tonsil group versus 26% in the BOT group (P = .009). Thirty percent of tonsil primaries has ≥N2c neck disease as compared to 54% of BOT. Incidence of distant metastases increases with advanced nodal classification, especially >N2c. CONCLUSION: Even though the locoregional controls are excellent with IMRT and chemotherapy, these patients continue to fail distantly, particularly significant for the BOT group and for nodal stage >N2c.

Prognostic biomarkers for HNSCC using quantitative real-time PCR and microarray analysis: ß-tubulin isotypes and the p53 interactome.

In 2014, more than 40,000 people in the United States will be diagnosed with head and neck squamous cell cancer (HNSCC) and nearly 8400 people will die of the disease (www.cancer.org/acs/groups). Little is known regarding molecular targets that might lead to better therapies and improved outcomes for these patients. The incorporation of taxanes into the standard cisplatin/5-fluouracil initial chemotherapy for HNSCC has been associated with improved response rate and survival. Taxanes target the ß-subunit of the tubulin heterodimers, the major protein in microtubules, and halt cell division at G2/M phase. Both laboratory and clinical research suggest a link between ß-tubulin expression and cancer patient survival, indicating that patterns of expression for ß-tubulin isotypes along with activity of tumor suppressors such as p53 or micro-RNAs could be useful prognostic biomarkers and could suggest therapeutic targets. © 2014 Wiley Periodicals, Inc.

Induction docetaxel, Cisplatin, and 5-Fluorouracil precludes definitive chemoradiotherapy in a substantial proportion of patients with head and neck cancer in a low socioeconomic status population.

OBJECTIVES: In this retrospective study we evaluate the tolerability and outcomes after induction chemotherapy for patients with predominately low socioeconomic status (SES) with locally advanced head and neck cancer (LAHNC). METHODS: One hundred eighteen patients with LAHNC of the hypopharynx, larynx, oral cavity, or oropharynx began curative intent therapy with induction cisplatin (75 or 100 mg/m), docetaxel (75 mg/m), and 5-fluorouracil (750 mg/m×5 d or 1000 mg/m×4 d; continuous infusion) every 3 weeks (DPF) for a planned 2 to 3 cycles. All patients were to receive curative radiotherapy with concurrent systemic therapy. Associations were tested using χ test, and survival estimates were calculated using the Kaplan-Meier method. RESULTS: Most patients (75.4%) were of low SES. Induction DPF was delivered for a median of 2 cycles (range, 1 to 3) and 14% of the patients (n=17) died during induction DPF. After DPF, 38.2% of patients were unable to complete or receive planned definitive therapy. Overall 15.3% of patients died during therapy, and mortality was associated with a Karnofsky performance status <80 (P=0.04). At 2 years the locoregional control was 52.7%, whereas the distant metastases free rate was 72.6%, and the overall survival rate was 34.1%. Low SES patients were less likely to achieve locoregional control (P=0.05) or survive (P=0.08). CONCLUSIONS: In this population of LAHNC patients of low SES with a high tumor burden and poor performance status, use of induction DPF was associated with 15.3% mortality during therapy and precluded 38.2% of patients from initiating or completing planned definitive therapy.

Locally advanced squamous cell carcinoma of the head and neck: CT texture and histogram analysis allow independent prediction of overall survival in patients treated with induction chemotherapy.

PURPOSE: To determine if computed tomographic (CT) texture and histogram analysis measurements of the primary mass are independently associated with overall survival in patients with locally advanced squamous cell carcinoma of the head and neck who were previously treated with cisplatin, 5-fluorouracil, and docetaxel (TPF) induction chemotherapy. MATERIALS AND METHODS: This institutional review board-approved retrospective study included 72 patients with locally advanced squamous cell carcinoma of the head and neck who were treated with induction TPF chemotherapy in 2004-2010. CT texture and histogram analysis of the primary mass on the pretherapy CT images were performed by using TexRAD software before and after application of spatial filters at different anatomic scales ranging from fine detail to coarse features. Cox proportional hazards models were used to examine the association between overall survival and the baseline CT imaging measurements and clinical variables. RESULTS: Primary mass entropy and skewness measurements with multiple spatial filters were associated with overall survival. Multivariate Cox regression analysis incorporating clinical and imaging variables indicated that primary mass size (hazard ratio [HR], 1.58 for each 1-cm increase; P = .018), N stage (HR, 8.77 for N3 vs N0 or N1; P = .002; HR, 4.99 for N3 vs N2; P = .001), and primary mass entropy (HR, 2.10 for each 0.5-unit increase; P = .036) and skewness (HR, 3.67 for each 1.0-unit increase; P = .009) measurements with the 1.0 spatial filter were independently associated with overall survival. CONCLUSION: Independent of tumor size, N stage, and other clinical variables, primary mass CT texture and histogram analysis parameters are associated with overall survival in patients with locally advanced squamous cell carcinoma of the head and neck who were treated with induction TPF. Online supplemental material is available for this article.

Two Metachronous Neoplasms in the Radiotherapy Fields of a Young Man With Familial Adenomatous Polyposis.

BACKGROUND: It is recognized that various radiation-induced malignancies often follow childhood radiotherapy. Radiation-induced neoplasms have been shown to occur with increased frequency in syndromes due to mutated tumor suppressor genes. There exist no recommendations for the management of cancer patients with germline APC gene mutations. Preclinical data suggest that APC gene mutations cause enhanced radiosensitivity, but no clinical observations exist that show that patients with this mutation are at higher risk for radiation-induced malignancies. RESULTS: We report the case of a 32-year-old man with a genetic diagnosis of familial adenomatous polyposis (FAP) who initially presented at age 10 with a medulloblastoma treated with radiotherapy and surgery. Radiation-induced papillary thyroid carcinoma followed 13 years later. Finally, radiation-induced soft tissue osteosarcoma occurred with widespread metastasis 20 years thereafter. CONCLUSIONS: This is the first report of 2 malignancies in the prior radiotherapy fields of a patient with a genetic diagnosis of FAP. More important, this suggests that APC-defective cells are at an enhanced sensitivity to the carcinogenic effects of radiotherapy compared with APC-proficient cells. This could argue for genetic screening in affected members of these families and for creation of treatment recommendations to more seriously consider the risks of radiation therapy.

What causes a prolactinoma to be aggressive or to become a pituitary carcinoma?

INTRODUCTION: Malignant prolactinoma is an exceedingly rare endocrine tumor and cannot be diagnosed on histological grounds alone. Similarly to other neuroendocrine tumors such as pheochromocytoma, the mitoses index, Ki-67, p53, and others are utilized in helping understand whether a tumor is benign or malignant or to better predict tumor behavior. We here present the unusual case of an unfortunate young man with an aggressive prolactinoma, the complications of which led to his premature death. CASE REPORT: A 25-year-old white man developed severe headaches, low energy, and decreased libido. A brain magnetic resonance imaging (MRI) showed a 4 x 3 x 2 cm pituitary tumor invading the left cavernous sinus. Laboratory findings revealed elevated prolactin (470 ng/mL) and adrenocorticotropic hormone (ACTH, 82 pg/ml) and decreased total testosterone (176 ng/dl). Visual fields showed superior quadrantanopia in the left eye. Transsphenoidal pituitary resection was undertaken. Pathology revealed a prolactinoma with atypical cells, diffuse p53 nuclear labeling, and a Ki-67 index of 23% (high). Postoperatively, prolactin remained elevated (725-891 ng/ml) and cabergoline was increased to 1 mg three times weekly, with serum prolactin further increasing to 3507 ng/ml five months postoperatively. Repeat MRI revealed extension of the tumor with optic chiasm compression and left orbit invasion. Because of acute left vision loss with ophthalmoplegia, an urgent left frontotemporal craniotomy and tumor resection were conducted. The Ki-67 index of the tumor was 24.8%, the mitotic figure immunostain phosphohistone-H3 positive. Sixty percent (60%) of tumor cells were positive for p53. Cabergoline was increased to 1 mg daily but prolactin remained elevated (770 ng/ml). The patient then underwent proton beam radiation to the area of concern involving the sella. Prolactin thereafter improved to 44 ng/ml. He then developed acute vision loss of the right eye with an MRI showing tumor in the right cavernous sinus. A 15 mm dural-based right temporal mass believed to be a metastasis was also noted. Following this scan, he was considered too high risk for debulking surgery and instead underwent gamma knife irradiation to the sella area. This shrank the right cavernous sinus tumor mass, while the right temporal mass increased in size. The patient developed blindness and left-sided weakness and required enteral feeding and tracheostomy after prolonged intubation. A trial of chemotherapy with temozolomide (350 mg daily for 5 days) near the end of his life was unsuccessful. He died on home hospice 31 months after his first surgery. CONCLUSION: Headaches, vision changes, and symptoms of androgen deficiency syndrome can be manifestations of an aggressive prolactinoma that might require surgery and additional medical therapy including cabergoline and temozolomide with an unpredictable time of survival.

Malignant seeding of percutaneous endoscopic gastrostomy tract in patient with head and neck cancer.

Malignant seeding of the percutaneous endoscopic gastrostomy (PEG) stoma is a rare and unusual complication of PEG performed in patients with head and neck cancer. Direct seeding of PEG stoma is believed to be the culprit. We present one such case of metastasis that lends support to an alternate hypothesis of vascular spread. First responders in such cases are usually not gastroenterologists and may include dieticians, primary care physicians, and radiologists. As such, we also provide pictures that would help the health care providers recognize this rare entity and manage appropriately and promptly.