Assessing cumulative acute toxicity of chemoradiotherapy in head and neck cancer with or without induction chemotherapy.

BACKGROUND: To compare cumulative acute toxicity in head and neck cancer patients treated with concurrent chemoradiotherapy alone (CCRT) versus induction chemotherapy (IC) followed by CCRT (I/CCRT). METHODS: 77 patients underwent definitive CCRT (30 I/CCRT and 47 CCRT). Toxicity was graded using the Common Terminology Criteria for Adverse Events version 4.0. Using the TAME adverse event reporting system, short-term toxicity (T) scores were generated for IC (TIC), CCRT (TCCRT), total treatment duration (TRx), post-treatment period (TPT) and an overall score (Toverall) from treatment start to post treatment period. RESULTS: Acute toxicity other than dysphagia, odynophagia, or dermatitis was reported in 90.0% and 66.0% of I/CCRT and CCRT patients, respectively (P=0.02). Compared to CCRT group, I/CCRT patients reported greater mean TRx (TRx: 2.11 vs. 2.87, P=0.01) and Toverall (Toverall: 2.60 vs. 3.70, P=0.003). CONCLUSION: I/CCRT patients reported more cumulative acute toxicity during treatment compared to CCRT patients using the TAME reporting system.

The influence of limited English proficiency on outcome in patients treated with radiotherapy for head and neck cancer.

OBJECTIVE: To evaluate how limited English proficiency affects treatment outcome in head and neck cancer (HNC) patients treated with curative intent radiation therapy (RT). METHODS: From 2004 to 2010, 131 patients with HNC underwent RT. Patient's self-reported primary language and race/ethnicity were obtained at hospital registration. English proficiency was categorized as being English proficient (EP) or limited English proficient (LEP). Race/ethnicity was categorized as white, black and other (Hispanics and Asians). Patients were evaluated for locoregional (LRC), distant control (DC), overall (OS) and disease-free (DFS) survival. RESULTS: Fewer LEP patients (60.0%) underwent chemoradiation compared to EP (83.8%), P=0.028. The three-year actuarial LRC for EP and LEP patients was 82.2% and 58.3%, respectively, P=0.038. LEP patients had an increased risk of locoregional failure on univariate Cox regression analysis (hazard ratio, HR 2.4, 95% CI, 1.0-5.8). No differences by English proficiency were seen for DC, OS and DFS. Race/ethnicity was not associated LRC, DC, OS and DFS. CONCLUSION: Inferior locoregional control was observed in LEP patients receiving RT for HNC. Potential health disparities as a result of limited English proficiency require further investigation. PRACTICE IMPLICATIONS: Patient education, use of culturally sensitive interpreter and patient navigation services, and improved patient compliance should be considered in head and neck cancer patients receiving complex multidisciplinary care.

Impact of neoadjuvant chemoradiotherapy followed by surgical resection on node-negative T3 and T4 non-small cell lung cancer.

OBJECTIVE: This study examined the impact of neoadjuvant chemotherapy and concurrent high-dose radiation therapy on survival in patients with node-negative T3 and T4 non-small cell lung cancer. METHODS: A total of 110 consecutive patients underwent surgical resection for invasive T3N0M0 (94 patients) and T4N0M0 (16 patients) non-small cell lung cancer between 1979 and 2008. Forty-seven patients received neoadjuvant chemotherapy and concurrent high-dose (5940 cGy) radiation therapy before resection (Chemo-RT group). Sixty-three patients underwent surgical resection without receiving induction chemoradiotherapy (Surg group), of whom 21 received neoadjuvant radiation, 19 received adjuvant radiation, 17 received surgery alone, 2 received adjuvant chemotherapy, 2 received adjuvant chemoradiotherapy, and 2 received brachytherapy. Survival of the Chemo-RT and Surg groups was compared using both crude and adjusted Cox proportional hazards models. RESULTS: The 5-year, 10-year, and median survivals were 61%, 50%, and 90 months, respectively, in the Chemo-RT group versus 22%, 14%, and 22 months, respectively, in the Surg group. Subjects in the Surg group had an increased risk of death (hazard ratio, 2.60; 95% confidence interval, 1.62-4.18; P = .0001) compared with the Chemo-RT group. After adjustment for potential confounding variables of age, sex, tumor size, tumor location, type of operation, and decade of care, subjects in the Surg group remained at increased risk of death (hazard ratio, 2.81; 95% confidence interval, 1.45-5.44, P = .002) compared with the Chemo-RT group. CONCLUSIONS: Aggressive treatment of node-negative invasive T3 and T4 NSCLC with induction chemoradiotherapy may significantly prolong survival. This approach should be evaluated in a prospective multicenter national trial.

Unusual tumor response and toxicity from radiation and concurrent erlotinib for non-small-cell lung cancer.

We report a case of a never-smoker female with non-small-cell lung cancer (NSCLC) who experienced a striking tumor response to combined low-dose radiation and the epidermal growth factor receptor inhibitor erlotinib, even though erlotinib alone was not effective in preventing tumor progression. Furthermore, the patient developed symptomatic pneumonitis, which is unusual for the small volume of lung that was exposed to a significant dose of radiation. This case demonstrates that combination therapy with radiation and erlotinib has the potential to significantly benefit a subset of patients with NSCLC in addition to those approximately 10% who have tumors which respond to erlotinib alone. It also highlights the potential risks of molecular targeted radiation therapy.

Phase II trial of erlotinib in gastroesophageal junction and gastric adenocarcinomas: SWOG 0127.

PURPOSE: A phase II trial of the oral epidermal growth factor receptor (EGFR) inhibitor erlotinib in patients with gastroesophageal adenocarcinomas stratified according to primary tumor location into two groups: gastroesophageal junction (GEJ)/cardia and distal gastric adenocarcinomas. PATIENTS AND METHODS: Patients with a histologically proven diagnosis of adenocarcinoma of the GEJ or stomach (ST) that was unresectable or metastatic; presence of measurable disease; no prior chemotherapy for advanced or metastatic cancer; Zubrod performance status (PS) of 0 to 1; and adequate renal, hepatic, and hematologic function were treated with erlotinib 150 mg/d orally. Patient characteristics were median age, GEJ-63 years, ST-64 years; sex, GEJ-84% male and 16% female, ST-60 male and 40 female; Zubrod PS, GEJ-25 had a PS of 0 and 18 had a PS 1, ST-13 had a PS of 0 and 12 had a PS of 1. RESULTS: Percentage of common toxicities were skin rash, 86% and 72%; fatigue, 51% and 44%; and AST/ALT elevation, 28% and 28%, respectively for GEJ and ST. There has been one confirmed complete response, three confirmed partial responses (PRs) and one unconfirmed PR for an overall response probability of 9% confirmed (95% CI, 3% to 22%), all occurring in GEJ stratum. No responses were observed in ST stratum. The median survival was 6.7 months in GEJ and 3.5 months in ST stratum. Neither intratumoral EGFR, transforming growth factor-alpha or phosphorylated Akt kinase expression nor plasma proteomic analyses were predictive of clinical outcome. No somatic mutations of the EGFR exons 18, 19, or 21 were detected and there was no gross amplification of EGFR by fluorescence in situ hybridization. CONCLUSION: Erlotinib is active in patients with GEJ adenocarcinomas, but appears inactive in gastric cancers. The molecular correlates examined were not predictive of the patient therapeutic response.