Purpose To evaluate the efficacy and adverse effects of image-guided stereotactic body radiation therapy (SBRT) in centrally/superiorly located non–small-cell lung cancer (NSCLC). Methods and Materials We delivered SBRT to 27 patients, 13 with stage I and 14 with isolated recurrent NSCLC. A central/superior location was defined as being within 2 cm of the bronchial tree, major vessels, esophagus, heart, trachea, pericardium, brachial plexus or vertebral body but 1 cm away from the spinal canal. All patients underwent four-dimensional CT–based planning, and daily CT-on-rail guided SBRT. The prescribed dose of 40 Gy (n=7) to the planning target volume was escalated to 50 Gy (n=20) in 4 consecutive days. Results With a median follow-up of 17 months (range, 6–40 months), the crude local control at the treated site was 100% using 50 Gy. However, three of seven patients had local recurrences when treated using 40 Gy. Of the patients with stage I disease, one (7.7%) and two (15.4%) developed mediastinal lymph node metastasis and distant metastases, respectively. Of the patients with recurrent disease, three (21.4%) and five (35.7%) developed mediastinal lymph node metastasis and distant metastasis, respectively. Four patients (28.6%) with recurrent disease but none with stage I disease developed grade 2 pneumonitis. Three patients (11.1%) developed grade 2–3 dermatitis and chest wall pain. One patient developed brachial plexus neuropathy. No esophagitis was noted in any patient. Conclusion Image-guided SBRT using 50 Gy delivered in four fractions is feasible and resulted in excellent local control.

Pathologic complete response in the resected esophagus can be achieved in approximately 30% of patients with locally advanced esophageal or gastroesophageal junction carcinoma after preoperative chemoradiation therapy. These patients tend to have a longer survival than those who have less than pathologic complete response. Post-chemoradiation esophageal biopsy (PCEB) is used to check for the presence of residual tumor before a definitive resection is performed, but the clinical significance of PCEB findings is not clear due to the possibility of sampling bias and the superficial nature of the specimen obtained. We evaluated the use of PCEB (defined as biopsy taken within 30 days before esophagectomy) in predicting residual cancer in post-treatment esophagectomy specimens. PCEB was performed in 65 of 183 (36%) patients with locally advanced esophageal or gastroesophageal junction carcinoma, who received preoperative chemoradiation therapy. The cancer status in PCEB was correlated with the residual cancer in the esophagectomy specimens. PCEB had no cancer in 80% (52 of 65) of patients (Bx-negative) and cancer in 20% (13 of 65) of patients (Bx-positive). There was no difference in the presence of residual cancer (either in esophagus or lymph node) in esophagectomy specimens between Bx-negative patients (77%, 40 of 52) or Bx-positive patients (92%, 12 of 13), P = 0.44. The positive predictive value of biopsy was 92% (12 of 13), negative predictive value 23% (12 of 52), sensitivity 23% (12 of 52) and specificity 92% (12 of 13). There was no difference in the residual cancer staging in the esophagectomy specimen between Bx-positive and Bx-negative patients. In contrast, residual metastatic carcinoma in lymph nodes was more frequent in Bx-positive patients (69.2%, 9 of 13) than in Bx-negative patients (28.8%, 15 of 52), P = 0.01. Our data suggest that PCEB is a specific but not a sensitive predictor of residual cancer following esophagectomy. Bx-positive patients tend to have more frequent residual tumor in lymph nodes. The utility of PCEB in predicting residual cancer in the lymph nodes needs to be explored further along with molecular predictors of response to preoperative therapy.

Purpose-The IGF1/IGF-1R signaling pathway has emerged as a potential determinant of radiation resistance in human cancer cell lines. Therefore we investigated the potency of monoclonal anti-IGF-1R antibody, A12, to enhance radiation response in upper respiratory tract cancers.Methods and Materials-Cell lines were assessed for IGF-1R expression and IGF1-dependent response to A12 or radiation using viability and clonogenic cancer cell survival assays. In vivo response of tumor xenografts to 10 or 20 Gy and A12 (0.25-2 mg × 3) was assessed using growth delay assays. Combined treatment effects were also analyzed by immunohistochemical assays for tumor cell proliferation, apoptosis, necrosis and VEGF expression at days 1 and 6 after start of treatment.Results-A12 enhanced the radiosensitivity of HN5 and FaDu head and neck carcinomas in vitro (p<0.05) and amplified the radioresponse of FaDu xenografts in a dose-dependent manner with enhancement factors ranging from 1.2 to 1.8 (p<0.01). Immunohistochemical analysis of FaDu xenografts demonstrated that A12 inhibited tumor cell proliferation (P<0.05) and VEGF expression. When A12 was combined with radiation, this resulted in apoptosis induction that persisted till 6 days from the start of treatment and in increased necrosis at day 1 (p<0.01, respectively). Combined treatment with A12 and radiation resulted in additive or sub-additive growth delay in H460 or A549 xenografts, respectively. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Conclusions-The results of this study strengthen the evidence for investigating how anti-IGF-1R strategies can be integrated into radiation and radiation-cetuximab regimen in the treatment of cancer of the upper aero-digestive tract cancers. NIH Public Access

This study compares clinical characteristics and survival between patients with and without laryngeal function (LF) preservation during surgical treatment for hypopharyngeal carcinoma. We retrospectively reviewed 485 cases of hypopharyngeal carcinoma treated at a single institution for analysis. There were 337 cases with and 148 cases without LF preservation after surgery. Preservation of LF was complete in 237 patients and partial in 100 patients. There were significant statistical differences between the preservation group and the group without preservation in T-stage (P < 0.001), overall staging (P < 0.001), and tumor sites (P < 0.001) except the N-stage (P = 0.240). The patients with LF preservation had significantly better overall survival (log-rank, P = 0.005) and a lower risk of death than those without LF preservation (HR 0.62, 95 % CI 0.43–0.97), after multivariable adjustment. Treatment with surgery in combination with radiotherapy is still the favorable choice for patients with hypopharyngeal carcinoma. The maximal restoration of pharyngoesophageal continuity and function improves survival for patients whose tumors are excised completely for the preservation of LF and laryngeal and pharyngeal reconstruction.Electronic supplementary materialThe online version of this article (doi:10.1007/s00405-014-3115-2) contains supplementary material, which is available to authorized users.

Concurrent cisplatin chemotherapy with postoperative EF-IMRT was safe and well tolerated. The acute and late toxicities are acceptable. The locoregional control rates are hopeful, although distant metastases continue to be the primary mode of failure. Postoperative EF-IMRT provides an opportunity to preserve endocrine function for patients with ovarian transposition.