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Abstract
Tumor staging systems for laryngeal cancer (LC) have been developed to assist in estimating
prognosis after treatment and comparing treatment results across institutions. While
the laryngeal TNM system has been shown to have prognostic information, varying cure
rates in the literature have suggested concern about the accuracy and effectiveness
of the T-classification in particular. To test the hypothesis that tumor volumes are
more useful than T classification, we conducted a retrospective review of 78 patients
with laryngeal cancer treated with radiation therapy at our institution. Using multivariable
analysis, we demonstrate the significant prognostic value of anatomic volumes in patients
with previously untreated laryngeal cancer. In this cohort, primary tumor volume (GTV
P), composite nodal volumes (GTV
N) and composite total volume (GTV
P + GTV
N = GTV
C) had prognostic value in both univariate and multivariate cox model analysis. Interestingly,
when anatomic volumes were measured from CT scans after a single cycle of induction
chemotherapy, all significant prognosticating value for measured anatomic volumes
was lost. Given the literature findings and the results of this study, the authors
advocate the use of tumor anatomic volumes calculated from pretreatment scans to supplement
the TNM staging system in subjects with untreated laryngeal cancer. The study found
that tumor volume assessment after induction chemotherapy is not of prognostic significance.
Survival has decreased among patients with laryngeal cancer during the past 2 decades in the United States. During this same period, there has been an increase in the nonsurgical treatment of laryngeal cancer. The objectives of this study were to identify trends in the demographics, management, and outcome of laryngeal cancer in the United States and to analyze factors contributing to the decreased survival. The authors conducted a retrospective, longitudinal study of laryngeal cancer cases. Review of the National Cancer Data Base (NCDB) revealed 158,426 cases of laryngeal squamous cell carcinoma (excluding verrucous carcinoma) diagnosed between the years 1985 and 2001. Analysis of these case records addressed demographics, management, and survival for cases grouped according to stage, site, and specific TNM classifications. This review of data from the NCDB analysis confirms the previously identified trend toward decreasing survival among patients with laryngeal cancer from the mid-1980s to mid-1990s. Patterns of initial management across this same period indicated an increase in the use of chemoradiation with a decrease in the use of surgery despite an increase in the use of endoscopic resection. The most notable decline in the 5-year relative survival between the 1985 to 1990 period and the 1994 to 1996 period occurred among advanced-stage glottic cancer, early-stage supraglottic cancers, and supraglottic cancers classified as T3N0M0. Initial treatment of T3N0M0 laryngeal cancer (all sites) in the 1994 to 1996 period resulted in poor 5-year relative survival for those receiving either chemoradiation (59.2%) or irradiation alone (42.7%) when compared with that of patients after surgery with irradiation (65.2%) and surgery alone (63.3%). In contrast, identical 5-year relative survival (65.6%) rates were observed during this same period for the subset of T3N0M0 glottic cancers initially treated with either chemoradiation or surgery with irradiation. The decreased survival recorded for patients with laryngeal cancer in the mid-1990s may be related to changes in patterns of management. Future studies are warranted to further evaluate these associations.
Assessment of radiation and chemotherapy efficacy for brain cancer patients is traditionally accomplished by measuring changes in tumor size several months after therapy has been administered. The ability to use noninvasive imaging during the early stages of fractionated therapy to determine whether a particular treatment will be effective would provide an opportunity to optimize individual patient management and avoid unnecessary systemic toxicity, expense, and treatment delays. We investigated whether changes in the Brownian motion of water within tumor tissue as quantified by using diffusion MRI could be used as a biomarker for early prediction of treatment response in brain cancer patients. Twenty brain tumor patients were examined by standard and diffusion MRI before initiation of treatment. Additional images were acquired 3 weeks after initiation of chemo- and/or radiotherapy. Images were coregistered to pretreatment scans, and changes in tumor water diffusion values were calculated and displayed as a functional diffusion map (fDM) for correlation with clinical response. Of the 20 patients imaged during the course of therapy, 6 were classified as having a partial response, 6 as stable disease, and 8 as progressive disease. The fDMs were found to predict patient response at 3 weeks from the start of treatment, revealing that early changes in tumor diffusion values could be used as a prognostic indicator of subsequent volumetric tumor response. Overall, fDM analysis provided an early biomarker for predicting treatment response in brain tumor patients.
As a general rule, surgery whenever possible, followed by irradiation is considered to be the standard treatment for cancer of the hypopharynx, thus sacrificing natural speech. In most patients, surgery includes removal of the larynx. A prospective, randomized phase III study was conducted by the European Organization for Research and Treatment of Cancer (EORTC) starting in 1990 to compare a larynx-preserving treatment (induction chemotherapy plus definitive, radiation therapy in patients who showed a complete response or surgery in those who did not respond) with conventional treatment (total laryngectomy with partial pharyngectomy, radical neck dissection, and postoperative irradiation) in previously untreated and operable patients with histologically proven squamous cell carcinomas of the pyriform sinus or aryepiglottic fold, but free of other cancers. Patients were randomly assigned to one of two treatment arms: 1) immediate surgery with postoperative radiotherapy (50-70 Gy) or 2) induction chemotherapy (cisplatin [100 mg/m2] given as a bolus intravenous injection on day 1, followed by infusion of fluorouracil [1000 mg/m2 per day] on days 1-5). An endoscopic evaluation was performed after each cycle of chemotherapy. After two cycles, only partial and complete responders received a third cycle. Patients with a complete response after two or three cycles of chemotherapy were treated thereafter by irradiation (70 Gy); nonresponding patients underwent conventional surgery with postoperative radiation (50-70 Gy). Salvage surgery was also performed when patients relapsed after chemotherapy and irradiation. The trial was designed to test the equivalence of the two treatment arms; i.e., the induction chemotherapy treatment would be judged equivalent to immediate surgery if the relative risk of death for induction chemotherapy compared with immediate surgery was significantly less than 1.43 using a one-sided hypothesis test at the .05 level of significance. Two hundred two patients entered the trial and were randomly assigned; only 194 were eligible for treatment (94 in the immediate-surgery arm and 100 in the induction-chemotherapy arm). In the induction-chemotherapy arm, complete response was seen in 52 (54%) of 97 patients with local disease (primary tumor) and in 31 (51%) of 61 patients with regional disease (involvement of the neck). Treatment failures at local, regional, and second primary sites occurred at approximately the same frequencies in the immediate-surgery arm (12%, 19%, and 16%, respectively) and in the induction-chemotherapy arm (17%, 23%, and 13%, respectively). In contrast, there were fewer failures at distant sites in the induction-chemotherapy arm than in the immediate-surgery arm (25% versus 36%, respectively; P = .041). The median duration of survival was 25 months in the immediate-surgery arm and 44 months in the induction-chemotherapy arm and, since the observed hazard ratio was 0.86 (logrank test, P = .006), which was significantly less than 1.43, the two treatments were judged to be equivalent. The 3- and 5-year estimates of retaining a functional larynx in patients treated in the induction-chemotherapy arm were 42% (95% confidence interval = 31%-53%) and 35% (95% confidence interval = 22%-48%), respectively. Larynx preservation without jeopardizing survival appears feasible in patients with cancer of the hypopharynx. On the basis of these observations, the EORTC has now accepted the use of induction chemotherapy followed by radiation as the new standard treatment in its future phase III larynx preservation trials.
[1
]Department of Otolaryngology/Head and Neck Surgery, The University of Michigan Health
System, 1903 Taubman Bldg, 1500 East Medical Center Drive, Ann Arbor, MI 48109, USA;
moeissa@
123456med.umich.edu
(M.R.I.);
fshalabi@
123456umich.edu
(F.L.S.)
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