Competing causes of death and second primary tumors in patients with locoregionally advanced head and neck cancer treated with chemoradiotherapy.

PURPOSE: The purpose of this retrospective analysis was to evaluate the emergence of second primary malignancies and the contribution of different causes of death to the outcome of patients with locoregionally advanced head and cancer receiving primary chemoradiotherapy. EXPERIMENTAL DESIGN: We studied 324 patients with stage IV squamous cell head and neck cancer who were enrolled on five consecutive multicenter Phase II studies of concurrent chemoradiotherapy. All of the regimens included concurrent 5-fluorouracil and hydroxyurea on an alternate week schedule with radiotherapy, either alone (FHX) or with cisplatin (C-FHX) or paclitaxel (T-FHX). The cumulative incidence of second primary tumors or death from any cause was estimated using methods of competing risk analysis. RESULTS: Median follow-up of surviving patients was 5.2 years (2-10.6 years). The 5-year overall survival and progression-free survival of the cohort were 46% and 65%, respectively. Causes of death and median time of occurrence were as follows: disease (n = 88; 1.5 years), treatment-associated acute or late complications (n = 30; 4 months), second primary tumors (n = 18; 3.5 years), comorbidities (n = 41; 1.9 years), and unknown (n = 20; 5.1 years). Predominant causes of death from comorbidities were cardiac and respiratory illnesses. Twenty-six patients (8%) developed a second primary tumor at a median time of 2.8 years (4 months to 10 years). The cumulative incidence of second primary tumors was 5%, 7%, and 13% at 3, 5, and 10 years, respectively. The most frequent site of second primaries was the lung (n = 13), followed by the esophagus (n = 3) and head and neck (n = 2) CONCLUSIONS: Patients with locoregionally advanced head and neck cancer treated with concurrent chemoradiotherapy are potentially curable but face significant risks of mortality from causes other than disease progression. Ameliorating toxicity, and implementing secondary screening and chemoprevention strategies are major goals in the management of head and neck cancer.     

Weekly carboplatin and paclitaxel followed by concomitant paclitaxel, fluorouracil, and hydroxyurea chemoradiotherapy: curative and organ-preserving therapy for advanced head and neck cancer.

PURPOSE: The paclitaxel, fluorouracil, and hydroxyurea regimen of paclitaxel, infusional fluorouracil, hydroxyurea, and twice-daily radiation therapy (TFHX) administered every other week has resulted in 3-year survival rates of 60% of stage IV patients. Locoregional and distant failure rates were 13% and 23%, respectively. To reduce distant failure rates, we added a brief course of induction chemotherapy to TFHX. PATIENTS AND METHODS: Sixty-nine patients received six weekly doses of carboplatin (AUC2) and paclitaxel (135 mg/m2) followed by five cycles of TFHX. RESULTS: Ninety-six percent had stage IV disease. Response to induction chemotherapy was partial response 52% and complete response (CR) 35%. Symptomatically, there was a significant reduction in mouth and throat pain. The most common grade 3 or 4 toxicity was neutropenia (36%). Best response following completion of TFHX was CR in 83%. Toxicities of TFHX consisted of grade 3 or 4 mucositis (74% and 2%) and dermatitis (47% and 14%). At a median follow-up of 28 months, locoregional or systemic disease progression were each noted in five patients. The overall 3-year progression-free survival was 80% (95% confidence interval [CI], 71% to 90%), and the 2- and 3-year overall survival rates were 77% (95% CI, 66% to 87%) and 70% (95% CI, 59% to 82%), respectively. At 12 months, five patients were completely feeding-tube dependent. CONCLUSION: Administration of carboplatin and paclitaxel before TFHX chemoradiotherapy results in high response activity and may decrease distant failure rates. Overall survival, progression, and organ preservation/functional outcome data support definitive evaluation of this approach.     

Induction chemotherapy followed by concomitant chemoradiotherapy in the treatment of locoregionally advanced nasopharyngeal cancer.

BACKGROUND: Since 1990, we have treated patients with advanced nasopharyngeal cancer with induction chemotherapy and concomitant chemoradiotherapy. We herein report the results of our experience. PATIENTS AND METHODS: From 1990 to 1999, 27 patients with locoregionally advanced nasopharyngeal cancer were treated with induction chemotherapy followed by concomitant chemoradiotherapy. Using the American Joint Committee on Cancer's 1992 stage classification, all patients were stage III (11%) or IV (89%). By histology, 63% were poorly differentiated carcinoma and 37% squamous cell carcinoma. The median age was 42 years. Three cycles of induction chemotherapy consisting of cisplatin, 5-fluorouracil, leucovorin and interferon-alpha2b were administered, followed by concomitant chemoradiotherapy consisting of seven cycles of 5-fluorouracil, hydroxyurea and once-daily radiotherapy (FHX) on a week-on week-off schedule. The median radiotherapy dose was 70 Gy. RESULTS: Clinical response to induction chemotherapy was 100%, 54.2% complete response (CR) and 45.8% partial response. Clinical and/or pathological (37% of all patients had post-treatment biopsy with or without neck dissection) CR after FHX was 100%. At a median follow-up of 52 months, three failures were observed. Two patients have died of disease, one of local failure and one of distant metastases. One patient is alive with an isolated rib metastasis. At 5 years, actuarial locoregional control is 93% and actuarial distant control 92%. The overall survival at 3 and 5 years is 88% and 77%, respectively. Four patients died of unrelated illnesses and had no evidence of disease with respect to their nasopharyngeal cancer. The progression-free survival at 3 and 5 years is 92% and 86%, respectively. Thirty-three per cent of patients required a reduction in the chemotherapy dose due to acute toxicity. Chronic toxicity was not observed, with all patients able to eat orally without dietary restrictions. CONCLUSIONS: Treatment of locoregionally advanced nasopharyngeal cancer with induction chemotherapy followed by concomitant chemoradiotherapy resulted in excellent overall survival with acceptable toxicity. These results are encouraging and warrant further investigation of intensified approaches.     

Macroglossia due to venous malformation

Massive vascular malformation involving tongue can cause significant functional impairment. In this report we describe a rare case of extensive venous malformation involving tongue leading to obstructive sleep apnoea, inability to speak, eat, severe discomfort due to exposure induced dryness and ulceration. Multimodality treatment approach comprising of sclerotherapy, electrocautery and radiation therapy was used in this case.     

Levonorgestrel-releasing intrauterine system vs. transcervical endometrial resection for dysfunctional uterine bleeding.

OBJECTIVE: To compare the acceptability, efficacy, adverse effects, and user satisfaction of a levonorgestrel intrauterine system (LNG-IUS) and transcervical resection of the endometrium (TCRE) for the treatment of dysfunctional uterine bleeding. METHOD: Of 50 women with a pictoral blood loss assessment chart (PBAC) score of 100 or greater, 25 had a LNG-IUS inserted (Mirena; Schering, Berlin, Germany) and 25 underwent TCRE. Procedure-related complications, PBAC score, hemoglobin levels, adverse effects, and rates of acceptability and satisfaction were recorded at 3-month intervals for a period of 12 months. RESULTS: At the end of 1 year there were a 97% and a 94% reduction in menstrual blood loss in the LNG-IUS and TCRE groups, respectively, and hemoglobin concentration had increased by 5.5% in the LNG-IUS group and 5.2% in the TCRE group. Adverse effects were similar in both groups except for systemic effects, which were seen only in the LNG-IUS group. Satisfaction rates were about 80% in the 2 groups. CONCLUSION: Both treatments were found to be equally effective but LNG-IUS placement requires less operator skill and entails no operative hazards, and the device provides effective contraception.     

Linear Stability Analysis and Gas Kinetic Scheme (GKS) Simulations of Instabilities in Compressible Plane Poiseuille Flow

The fundamental nature of flow instability in wall bounded flows changes with Mach number. The objectives of this study are two-fold, (i) compute the instability modes in high Mach number Poiseuille flows using linear stability analysis (LSA) and, (ii) perform direct numerical simulations (DNS) of the instability development using a solver based on gas kinetic method (GKM) for the purpose of code validation by comparison against LSA results. The LSA and DNS are performed for the case of Poiseuille flow over a range of Mach numbers – from moderately supersonic to hypersonic speeds. First, LSA is employed to identify the most unstable mode over the range of Mach numbers. We then perform two sets of GKM-DNS to corroborate the LSA results over the Mach number range. In the first set of simulations, the background field is initially perturbed with the most unstable mode identified by LSA and the evolution is monitored. It is shown that GKM-DNS accurately captures the exponential growth in kinetic energy for all Mach numbers. The second set of GKM-DNS simulations is performed by superposing the background pressure field with random initial perturbations. After an initial transient period, the modes predicted by LSA dominate the DNS flow field evolution. The wave-vector and mode shapes of the dominant instability are well replicated by GKM-DNS at each Mach number. These insights in the linear regime of high speed Poiseuille flow and validation of GKM are important for understanding and simulating wall bounded flows.