Treatment of oropharyngeal squamous cell carcinoma with IMRT: patterns of failure after concurrent chemoradiotherapy and sequential therapy.

BACKGROUND: The optimal management of oropharyngeal squamous cell carcinoma (OPSCC) is controversial. Modern radiotherapy typically employs intensity-modulated radiation therapy (IMRT), and herein, we report the Dana-Farber Cancer Institute (DFCI) experience with IMRT-based treatment of OPSCC. DESIGN: Retrospective study of all patients treated at DFCI for OPSCC with definitive or adjuvant IMRT between 8/04 and 8/09. The primary end point was overall survival (OS); secondary end points were locoregional control (LRC) and freedom from distant metastases (FFDM). Propensity score matching was used to create concurrent chemoradiotherapy (CCRT) and sequential therapy (ST) cohorts equally balanced for patient and disease characteristics. RESULTS: One hundred and sixty-three patients were included with 75% presenting with stage IV disease. Fifty-six patients (34%) were treated with ST. The three-year actuarial OS, LRC, and FFDM rates for the entire cohort/ST subset were 86%/89%, 86%/87%, and 88%/93%, respectively. There were no differences in OS, LRC, or FFDM between CCRT and ST in the propensity-matched cohort. CONCLUSIONS: IMRT was associated with excellent OS, LRC, and FFDM. Although the results following ST were superb, there was no obvious benefit to ST after adjustment for selection bias. We recommend that ST be reserved for medically fit patients with a high risk of distant metastases.

Cost-effectiveness of CT and PET-CT for determining the need for adjuvant neck dissection in locally advanced head and neck cancer.

BACKGROUND: Patients with node-positive head and neck squamous cell carcinomas (HNC) have a significant risk of residual disease (RD) in the neck after treatment, despite optimal chemoradiotherapy (CRT). Adjuvant neck dissection (ND) after CRT has been considered standard treatment, but its morbidity has led investigators to consider using post-CRT imaging to determine the need for surgery. We analyzed the cost-effectiveness of computed tomography (CT) and positron emission tomography-computed tomography (PET-CT) as predictors of the need for ND compared with ND for all patients. MATERIALS AND METHODS: We developed a Markov model to describe health states in the 5 years after CRT for HNC in a 50-year-old man. We compared three strategies: dissect all patients, dissect patients with RD on CT, and dissect patients with RD on PET-CT. Probabilistic sensitivity analyses were carried out to model uncertainty in PET-CT performance, up-front and salvage dissection costs, and patient utilities. RESULTS: ND only for patients with RD on PET-CT was the dominant strategy over a wide range of realistic and exaggerated assumptions. Probabilistic sensitivity analyses confirmed that the PET-CT strategy was almost certainly cost-effective at a societal willingness-to-pay threshold of $500,000/quality-adjusted life year. CONCLUSION: Adjuvant ND reserved for patients with RD on PET-CT is the dominant and cost-effective strategy.

Prognostic significance of mid- and post-ABVD PET imaging in Hodgkin's lymphoma: the importance of involved-field radiotherapy.

BACKGROUND: Although positron emission tomography (PET) response to chemotherapy (CT) has prognostic significance in Hodgkin's lymphoma (HL), it is unclear whether patients with 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG)-PET positivity during and/or after CT can be rendered disease free with consolidative involved-field radiotherapy (IFRT). METHODS: Patients with HL treated with adriamycin, bleomycin, vinblastine and dacarbazine (ABVD)-based CT and radiotherapy (RT) at our institution from January 2000 to March 2007 were eligible. All patients had either a post-treatment PET or PET-CT before initiation of RT or a negative midtreatment PET or PET-CT. The primary end point was failure-free survival (FFS) for patients with and without residual FDG avidity after ABVD. The treatment outcome of patients with interim PET positivity during CT was also reported. RESULTS: Seventy-three patients were included in this study. Twenty patients (out of 46) were PET positive on interim PET, and 13 patients (out of 73) were PET positive at the conclusion of CT. At a median follow-up of 3.4 years for surviving patients, the 2-year FFSs for patients PET-negative versus PET-positive disease after ABVD were 95% and 69%, respectively (P < 0.01). On bivariable Cox regression, post-ABVD positivity (hazard ratio 4.8, P = 0.05) was predictive of disease recurrence after controlling for bulky disease. Of the 20 patients with interim PET positivity, three recurred, with a 2-year FFS of 85%. Among the 13 patients with interim PET positivity, but became PET negative at the completion of CT, the 2-year FFS was 92%. CONCLUSION: Sixty-nine per cent of patients with residual FDG avidity after ABVD were free of disease after consolidative RT, indicating a majority of patients with persistent lymphoma can be cured by sterilizing this PET-positive disease.

Regional differences in gastric acidity and antacid distribution: is a single pH electrode sufficient?

UNLABELLED: Accurate measurement of intragastric acidity has both clinical and investigational importance in studying gastric pathophysiology. OBJECTIVES: The aims of this study were fourfold: (1) to investigate whether regional differences in intragastric acidity exist; (2) to determine intragastric acidity after a standard antacid was administered in both the fasting and fed states; (3) to monitor gastric emptying of and anatomic distribution of radiolabeled antacid during fasting and postprandial periods; and (4) to determine whether the regional effects of ingested antacid correlated with the anatomic distribution of the antacid. METHODS: Eight normal male volunteers were studied after fluoroscopically guided nasogastric placement of a tube assembly containing four pH electrodes, with one electrode in each quartile of the stomach. Simultaneous pH readings were made from the four electrodes while fasting, after administration of fasting antacid (30 ml, 79 mEq buffering capacity), postprandially, and after postprandial antacid ingestion. All subjects repeated the protocol on a separate day, five of them using radiolabeled antacid. Gastric emptying and gastric distribution over time of radiolabeled antacid were determined for comparison to regional intragastric acidity. RESULTS: Intragastric acidity varied regionally over time in response to meals and to fasting and postprandial antacid. In the fasting state, intragastric acidity returned to baseline after antacid ingestion in a proximal to distal (cardia to antrum) sequence, while postprandial antacid resulted in a return to baseline acidity in a distal to proximal (antrum to cardia) sequence. Radiolabeled antacid distribution paralleled intragastric pH and hydrogen ion concentration in the fasting state, with 82% of the antacid localizing in the distal half of the stomach within the first minute after antacid ingestion. Postprandially, the greatest initial and most prolonged antacid buffering effect occurred proximally, correlating with the presence of radiolabeled antacid. Postprandial antacid remained in the stomach for a longer time (T1/2 = 93.1 +/- 23.4 min) compared with fasting antacid (T1/2 = 23.6 +/- 11.1 min). CONCLUSIONS: Measurement of acidity in the four quartiles of the stomach demonstrated regional variation in response to both food and a standard antacid. A single pH electrode does not detect regional intragastric pH differences.

A single intragastric pH electrode does not accurately measure intragastric acidity.

OBJECTIVES: Recent studies have raised concerns about the validity of using a single intragastric pH electrode to measure gastric acidity accurately and reproducibly. The aim of this study was to compare simultaneous intragastric pH measurements obtained from an indwelling glass pH electrode to those determined by aspirations from the gastric pool and from ex vivo measurement. METHODS: Twenty two normal volunteers were studied after fluoroscopically guided placement of a combined nasogastric tube-pH probe assembly. Simultaneous intragastric pH electrode and aspirate pH determinations were made basally for 120 min after administration of 15 ml of antacid (40 mEq buffering capacity) and for another 120 min an hour postprandially after administration of a second 15-ml dose of antacid. Gastric acid concentration (pH) measurements were recorded every 15 min during the following study protocols: 1) fasting baseline (30 min); 2) fasting antacid (120 min); 3) test meal (60 min); and 4) postprandial antacid (120 min). RESULTS: Intragastric pH was consistently and significantly lower as measured by intragastric pH electrode than by aspiration. Baseline hydrogen ion concentration ([H+]) was 4.3 times higher by direct electrode measurement than by aspirate. Antacid-administered fasting decreased [H+] maximally at 15 min to 48% and 82% of baseline by electrode and aspiration, respectively. The minimal residual intragastric [H+] after fasting antacid was 12.4 times higher by electrode than by aspiration. Postprandial antacid maximally reduced [H+] by 46% at 15 min when recorded using an electrode compared with 60% at 30 min by aspiration. Correlation coefficients for intragastric electrode [H+] versus aspiration [H+] were 0.26 (p = 0.253), 0.61 (p < 0.001), 0.56 (p < 0.01), and 0.31 (p < 0.001), for baseline, fasting antacid, meal, and postprandial antacid, respectively. CONCLUSIONS: Quantitative evaluations of intragastric acidity (pH) using an intragastric pH electrode and aspiration of gastric juice may yield remarkably different results. Studies that rely on a single intragastric electrode to quantitate intragastric acidity may be highly inaccurate.