William H. Morrison

Bio: William H. Morrison is an academic researcher from University of Texas MD Anderson Cancer Center. The author has contributed to research in topics: Radiation therapy & Head and neck cancer. The author has an hindex of 68, co-authored 253 publications receiving 16901 citations.

Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer

Abstract: Background Induction chemotherapy with cisplatin plus fluorouracil followed by radiotherapy is the standard alternative to total laryngectomy for patients with locally advanced laryngeal cancer. The value of adding chemotherapy to radiotherapy and the optimal timing of chemotherapy are unknown. Methods We randomly assigned patients with locally advanced cancer of the larynx to one of three treatments: induction cisplatin plus fluorouracil followed by radiotherapy, radiotherapy with concurrent administration of cisplatin, or radiotherapy alone. The primary end point was preservation of the larynx. Results A total of 547 patients were randomly assigned to one of the three study groups. The median follow-up period was 3.8 years. At two years, the proportion of patients who had an intact larynx after radiotherapy with concurrent cisplatin (88 percent) differed significantly from the proportions in the groups given induction chemotherapy followed by radiotherapy (75 percent, P=0.005) or radiotherapy alone (70 ...

Long-Term Results of RTOG 91-11: A Comparison of Three Nonsurgical Treatment Strategies to Preserve the Larynx in Patients With Locally Advanced Larynx Cancer

Abstract: Purpose To report the long-term results of the Intergroup Radiation Therapy Oncology Group 91-11 study evaluating the contribution of chemotherapy added to radiation therapy (RT) for larynx preservation. Patients and Methods Patients with stage III or IV glottic or supraglottic squamous cell cancer were randomly assigned to induction cisplatin/fluorouracil (PF) followed by RT (control arm), concomitant cisplatin/RT, or RT alone. The composite end point of laryngectomy-free survival (LFS) was the primary end point. Results Five hundred twenty patients were analyzed. Median follow-up for surviving patients is 10.8 years. Both chemotherapy regimens significantly improved LFS compared with RT alone (induction chemotherapy v RT alone: hazard ratio [HR], 0.75; 95% CI, 0.59 to 0.95; P = .02; concomitant chemotherapy v RT alone: HR, 0.78; 95% CI, 0.78 to 0.98; P = .03). Overall survival did not differ significantly, although there was a possibility of worse outcome with concomitant relative to induction chemother...

Quantification of volumetric and geometric changes occurring during fractionated radiotherapy for head-and-neck cancer using an integrated CT/linear accelerator system.

Abstract: Purpose Many patients receiving fractionated radiotherapy (RT) for head-and-neck cancer have marked anatomic changes during their course of treatment, including shrinking of the primary tumor or nodal masses, resolving postoperative changes/edema, and changes in overall body habitus/weight loss. We conducted a pilot study to quantify the magnitude of these anatomic changes with systematic CT imaging. Methods and materials Fourteen assessable patients were enrolled in this pilot study. Eligible patients had to have a pathologic diagnosis of head-and-neck cancer, be treated with definitive external beam RT, and had have gross primary and/or cervical nodal disease measuring at least 4 cm in maximal diameter. All patients were treated using a new commercial integrated CT-linear accelerator system (EXaCT) that allows CT imaging at the daily RT sessions while the patient remains immobilized in the treatment position. CT scans were acquired three times weekly during the entire course of RT, and both gross tumor volumes (GTVs: primary tumor and involved lymph nodes) and normal tissues (parotid glands, spinal canal, mandible, and external contour) were manually contoured on every axial slice. Volumetric and positional changes relative to a central bony reference (the center of mass of the C2 vertebral body) were determined for each structure. Results Gross tumor volumes decreased throughout the course of fractionated RT, at a median rate of 0.2 cm 3 per treatment day (range, 0.01–1.95 cm 3 /d). In terms of the percentage of the initial volume, the GTVs decreased at a median rate of 1.8%/treatment day (range, 0.2–3.1%/d). On the last day of treatment, this corresponded to a median total relative loss of 69.5% of the initial GTV (range, 9.9–91.9%). In addition, the center of the mass of shrinking tumors changed position with time, indicating that GTV loss was frequently asymmetric. At treatment completion, the median center of the mass displacement (after corrections for daily setup variation) was 3.3 mm (range, 0–17.3 mm). Parotid glands also decreased in volume (median, 0.19 cm 3 /d range, 0.04–0.84 cm 3 /d), and generally shifted medially (median, 3.1 mm; range, 0–9.9 mm) with time. This medial displacement of the parotid glands correlated highly with the weight loss that occurred during treatment. Conclusion Measurable anatomic changes occurred throughout fractionated external beam RT for head-and-neck cancers. These changes in the external contour, shape, and location of the target and critical structures appeared to be significant during the second half of treatment (after 3–4 weeks of treatment) and could have potential dosimetric impact when highly conformal treatment techniques are used. These data may, therefore, be useful in the development of an adaptive RT scheme (periodic adjustment of the conformal treatment plan) that takes into account such treatment-related anatomic changes. In theory, such a strategy would maximize the therapeutic ratio of RT.

Intensity-Modulated Radiation Therapy With or Without Chemotherapy for Nasopharyngeal Carcinoma: Radiation Therapy Oncology Group Phase II Trial 0225

Abstract: Purpose To investigate the feasibility of intensity-modulated radiation therapy (IMRT) with or without chemotherapy, and to assess toxicities, failure patterns, and survivals in patients with nasopharyngeal carcinoma (NPC). Patients and Methods Radiation consisted of 70 Gy given to the planning target volumes of primary tumor plus any N+ disease and 59.4 Gy given to subclinical disease, delivered over 33 treatment days. Patients with stage T2b or greater or with N+ disease also received concurrent cisplatin (100 mg/m2) on days 1, 22, and 43 followed by adjuvant cisplatin (80 mg/m2) on day 1; fluorouracil (1,000 mg/m2/d) on days 1 through 4 administered every 4 weeks for three cycles. Tumor, clinical status, and acute/late toxicities were assessed. The primary objective was to test the transportability of IMRT to a multi-institutional setting. Results Between February 2003 and November 2005, 68 patients with stages I through IVB NPC (of which 93.8% were WHO types 2 and 3) were enrolled. Prescribed IMRT (ta...

Randomized trial addressing risk features and time factors of surgery plus radiotherapy in advanced head-and-neck cancer

Abstract: Purpose: A multi-institutional, prospective, randomized trial was undertaken in patients with advanced head-and-neck squamous cell carcinoma to address ( 1 ) the validity of using pathologic risk features, established from a previous study, to determine the need for, and dose of, postoperative radiotherapy (PORT); ( 2 ) the impact of accelerating PORT using a concomitant boost schedule; and ( 3 ) the importance of the overall combined treatment duration on the treatment outcome. Methods and Materials: Of 288 consecutive patients with advanced disease registered preoperatively, 213 fulfilled the trial criteria and went on to receive therapy predicated on a set of pathologic risk features: no PORT for the low-risk group ( n = 31); 57.6 Gy during 6.5 weeks for the intermediate-risk group ( n = 31); and, by random assignment, 63 Gy during 5 weeks ( n = 76) or 7 weeks ( n = 75) for the high-risk group. Patients were irradiated with standard techniques appropriate to the site of disease and likely areas of spread. The study end points were locoregional control (LRC), survival, and morbidity. Results: Patients with low or intermediate risks had significantly higher LRC and survival rates than those with high-risk features ( p = 0.003 and p = 0.0001, respectively), despite receiving no PORT or lower dose PORT, respectively. For high-risk patients, a trend toward higher LRC and survival rates was noted when PORT was delivered in 5 rather than 7 weeks. A prolonged interval between surgery and PORT in the 7-week schedule was associated with significantly lower LRC ( p = 0.03) and survival ( p = 0.01) rates. Consequently, the cumulative duration of combined therapy had a significant impact on the LRC ( p = 0.005) and survival ( p = 0.03) rates. A 2-week reduction in the PORT duration by using the concomitant boost technique did not increase the late treatment toxicity. Conclusions: This Phase III trial established the power of risk assessment using pathologic features in determining the need for, and dose of, PORT in patients with advanced head-and-neck squamous cell cancer in a prospective, multi-institutional setting. It also revealed the impact of the overall treatment time in the combination of surgery and PORT on the outcome in high-risk patients and showed that PORT acceleration without a reduction in dose by a concomitant boost regimen did not increase the late complication rate. These findings emphasize the importance of coordinated interdisciplinary care in the delivery of combined surgery and RT.

2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer.

Abstract: Background: Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Since the American Thyroid Association's (ATA's) guidelines for the management of these disorders were revised in 2009, significant scientific advances have occurred in the field. The aim of these guidelines is to inform clinicians, patients, researchers, and health policy makers on published evidence relating to the diagnosis and management of thyroid nodules and differentiated thyroid cancer. Methods: The specific clinical questions addressed in these guidelines were based on prior versions of the guidelines, stakeholder input, and input of task force members. Task force panel members were educated on knowledge synthesis methods, including electronic database searching, review and selection of relevant citations, and critical appraisal of selected studies. Published English language articles on adults were eligible for inclusion. The American College of Physicians Guideline Gr...

Revised American Thyroid Association Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer

Abstract: Background: Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Since the publication of the American Thyroid Association's guidelines for the management of these disorders was published in 2006, a large amount of new information has become available, prompting a revision of the guidelines. Methods: Relevant articles through December 2008 were reviewed by the task force and categorized by topic and level of evidence according to a modified schema used by the United States Preventative Services Task Force. Results: The revised guidelines for the management of thyroid nodules include recommendations regarding initial evaluation, clinical and ultrasound criteria for fine-needle aspiration biopsy, interpretation of fine-needle aspiration biopsy results, and management of benign thyroid nodules. Recommendations regarding the initial management of thyroid cancer include those relating to optimal surgical management, radioiodine remnant ablation, a...

Radiotherapy plus Cetuximab for Squamous-Cell Carcinoma of the Head and Neck

Abstract: BACKGROUND We conducted a multinational, randomized study to compare radiotherapy alone with radiotherapy plus cetuximab, a monoclonal antibody against the epidermal growth factor receptor, in the treatment of locoregionally advanced squamous-cell carcinoma of the head and neck. METHODS Patients with locoregionally advanced head and neck cancer were randomly assigned to treatment with high-dose radiotherapy alone (213 patients) or high-dose radiotherapy plus weekly cetuximab (211 patients) at an initial dose of 400 mg per square meter of body-surface area, followed by 250 mg per square meter weekly for the duration of radiotherapy. The primary end point was the duration of control of locoregional disease; secondary end points were overall survival, progression-free survival, the response rate, and safety. RESULTS The median duration of locoregional control was 24.4 months among patients treated with cetuximab plus radiotherapy and 14.9 months among those given radiotherapy alone (hazard ratio for locoregional progression or death, 0.68; P = 0.005). With a median follow-up of 54.0 months, the median duration of overall survival was 49.0 months among patients treated with combined therapy and 29.3 months among those treated with radiotherapy alone (hazard ratio for death, 0.74; P = 0.03). Radiotherapy plus cetuximab significantly prolonged progression-free survival (hazard ratio for disease progression or death, 0.70; P = 0.006). With the exception of acneiform rash and infusion reactions, the incidence of grade 3 or greater toxic effects, including mucositis, did not differ significantly between the two groups. CONCLUSIONS Treatment of locoregionally advanced head and neck cancer with concomitant highdose radiotherapy plus cetuximab improves locoregional control and reduces mortality without increasing the common toxic effects associated with radiotherapy to the head and neck. (ClinicalTrials.gov number, NCT00004227.)

Decoding tumour phenotype by noninvasive imaging using a quantitative radiomics approach

Abstract: Human cancers exhibit strong phenotypic differences that can be visualized noninvasively by medical imaging. Radiomics refers to the comprehensive quantification of tumour phenotypes by applying a large number of quantitative image features. Here we present a radiomic analysis of 440 features quantifying tumour image intensity, shape and texture, which are extracted from computed tomography data of 1,019 patients with lung or head-and-neck cancer. We find that a large number of radiomic features have prognostic power in independent data sets of lung and head-and-neck cancer patients, many of which were not identified as significant before. Radiogenomics analysis reveals that a prognostic radiomic signature, capturing intratumour heterogeneity, is associated with underlying gene-expression patterns. These data suggest that radiomics identifies a general prognostic phenotype existing in both lung and head-and-neck cancer. This may have a clinical impact as imaging is routinely used in clinical practice, providing an unprecedented opportunity to improve decision-support in cancer treatment at low cost.

Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck.

Abstract: After a median follow-up of 45.9 months, the rate of local and regional control was significantly higher in the combined-therapy group than in the group given radiotherapy alone (hazard ratio for local or regional recurrence, 0.61; 95 percent confidence interval, 0.41 to 0.91; P=0.01). The estimated two-year rate of local and regional control was 82 percent in the combined-therapy group, as compared with 72 percent in the radiotherapy group. Disease-free survival was significantly longer in the combined-therapy group than in the radiotherapy group (hazard ratio for disease or death, 0.78; 95 percent confidence interval, 0.61 to 0.99; P=0.04), but overall survival was not (hazard ratio for death, 0.84; 95 percent confidence interval, 0.65 to 1.09; P=0.19). The incidence of acute adverse effects of grade 3 or greater was 34 percent in the radiotherapy group and 77 percent in the combined-therapy group (P<0.001). Four patients who received combined therapy died as a direct result of the treatment. conclusions Among high-risk patients with resected head and neck cancer, concurrent postoperative chemotherapy and radiotherapy significantly improve the rates of local and regional control and disease-free survival. However, the combined treatment is associated with a substantial increase in adverse effects.