Concurrent chemotherapy and intensity-modulated radiotherapy for locoregionally advanced laryngeal and hypopharyngeal cancers.

PURPOSE: To perform a retrospective review of laryngeal/hypopharyngeal carcinomas treated with concurrent chemotherapy and intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: Between January 2002 and June 2005, 20 laryngeal and 11 hypopharyngeal carcinoma patients underwent IMRT with concurrent platinum-based chemotherapy; most patients had Stage IV disease. The prescription of the planning target volume for gross, high-risk, and low-risk subclinical disease was 70, 59.4, and 54 Gy, respectively. Acute/late toxicities were retrospectively scored using the Common Toxicity Criteria scale. The 2-year local progression-free, regional progression-free, laryngectomy-free, distant metastasis-free, and overall survival rates were calculated using the Kaplan-Meier method. RESULTS: The median follow-up of the living patients was 26 months (range, 17-58 months). The 2-year local progression-free, regional progression-free, laryngectomy-free, distant metastasis-free, and overall survival rate was 86%, 94%, 89%, 92%, and 63%, respectively. Grade 2 mucositis or higher occurred in 48% of patients, and all experienced Grade 2 or higher pharyngitis during treatment. Xerostomia continued to decrease over time from the end of RT, with none complaining of Grade 2 toxicity at this analysis. The 2-year post-treatment percutaneous endoscopic gastrostomy-dependency rate for those with hypopharyngeal and laryngeal tumors was 31% and 15%, respectively. The most severe late complications were laryngeal necrosis, necrotizing fascitis, and a carotid rupture resulting in death 3 weeks after salvage laryngectomy. CONCLUSION: These preliminary results have shown that IMRT achieved encouraging locoregional control of locoregionally advanced laryngeal and hypopharyngeal carcinomas. Xerostomia improved over time. Pharyngoesophageal stricture with percutaneous endoscopic gastrostomy dependency remains a problem, particularly for patients with hypopharyngeal carcinoma and, to a lesser extent, those with laryngeal cancer. Strategies using IMRT to limit the dose delivered to the esophagus/inferior constrictor musculature without compromising target coverage might be useful to further minimize this late complication.

Does registration of PET and planning CT images decrease interobserver and intraobserver variation in delineating tumor volumes for non-small-cell lung cancer?

PURPOSE: To compare tumor volume delineation using registered positron emission tomography (PET)/CT vs. side-by-side image sets. METHODS AND MATERIALS: A total of 19 patients with non-small-cell lung cancer had 18-fluorine-deoxyglucose (FDG)-PET scans registered with planning CT scans. The disease was Stage I-II in 26%, IIIA in 42%, and IIIB in 32%. Two radiation oncologists contoured 9 tumor volumes using registered images (registered) and 10 using separate FDG-PET images as a guide (nonregistered). A third physician, who had done the treatment planning for these patients a median of 40 months before using registered images, repeated all contours: 10 on registered images (registered/registered) and 9 without registration (registered/nonregistered). Each pair of volumes (A and B) was compared. Quantitative comparison used the concordance index, (A intersection B)/(A union or logical sum B). For qualitative analysis, pairs of volumes were projected onto digitally reconstructed radiographs. The differences were graded as insignificant, minor, moderate, or major. RESULTS: The median interobserver percentage of concordance among nonregistered pairs was 61% vs. 70% in the registered group (p <0.05). On qualitative analysis, in the nonregistered group, the differences were insignificant in 5, minor in 3, and moderate in 2 of 10. The differences in the registered group were insignificant in 7 and minor in 2 of 9. The median intraobserver percentage of concordance in the registered/nonregistered group was 58% vs. 71% in the registered/registered group (p = 0.10). On qualitative analysis, the intraobserver differences in the registered/nonregistered group were insignificant in 2, minor in 2, moderate in 0, and major in 5 of 9. In the registered/registered group, the differences were insignificant in 2, minor in 6, moderate in 2, and major in 0 of 10. CONCLUSION: Registration of FDG-PET and planning CT images results in greater consistency in tumor volume delineation.

Intensity-modulated proton therapy for elective nodal irradiation and involved-field radiation in the definitive treatment of locally advanced non-small-cell lung cancer: a dosimetric study.

BACKGROUND: Photon involved-field (IF) radiation therapy (IFRT), the standard for locally advanced (LA) non-small cell lung cancer (NSCLC), results in favorable outcomes without increased isolated nodal failures, perhaps from scattered dose to elective nodal stations. Because of the high conformality of intensity-modulated proton therapy (IMPT), proton IFRT could increase nodal failures. We investigated the feasibility of IMPT for elective nodal irradiation (ENI) in LA-NSCLC. PATIENTS AND METHODS: IMPT IFRT plans were generated to the same total dose of 66.6-72 Gy received by 20 LA-NSCLC patients treated with photon IFRT. IMPT ENI plans were generated to 46 cobalt Gray equivalent (CGE) to elective nodal planning treatment volumes (PTV) plus 24 CGE to IF-PTVs. RESULTS: Proton IFRT and ENI improved the IF-PTV percentage of volume receiving 95% of the prescribed dose (D95) by 4% (P < .01) compared with photon IFRT. All evaluated dosimetric parameters improved significantly with both proton plans. The lung percentage of volume receiving 20 Gy/CGE (V20) and mean lung dose decreased 18% (P < .01) and 36% (P < .01), respectively, with proton IFRT, and 11% (P = .03) and 26% (P < .01) with ENI. The mean esophagus dose decreased 16% with IFRT and 12% with ENI; heart V25 decreased 63% with both (all P < .01). CONCLUSION: This study demonstrates the feasibility of IMPT for LA-NSCLC ENI. Potential decreased toxicity indicates that IMPT could allow ENI while maintaining a favorable therapeutic ratio compared with photon IFRT.

Follow-up of head and neck cancer patients post-radiotherapy.

Diverging opinions exist regarding follow-up studies post-radiotherapy for head and neck cancer. This report describes the efficacy of follow-up physical examinations, thyroid function tests and screening chest X-rays in post-radiotherapy patients in a practice analysis schema. This analysis suggests that physical examination and thyroid function testing remain valid parts of routine follow-up for head and neck cancer patients; chest X-rays appear less vital unless the patient's clinical situation warrants aggressive therapy of a second primary lung cancer.

Predicted rates of secondary malignancies from proton versus photon radiation therapy for stage I seminoma.

PURPOSE: Photon radiotherapy has been the standard adjuvant treatment for stage I seminoma. Single-dose carboplatin therapy and observation have emerged as alternative options due to concerns for acute toxicities and secondary malignancies from radiation. In this institutional review board-approved study, we compared photon and proton radiotherapy for stage I seminoma and the predicted rates of excess secondary malignancies for both treatment modalities. METHODS AND MATERIAL: Computed tomography images from 10 consecutive patients with stage I seminoma were used to quantify dosimetric differences between photon and proton therapies. Structures reported to be at increased risk for secondary malignancies and in-field critical structures were contoured. Reported models of organ-specific radiation-induced cancer incidence rates based on organ equivalent dose were used to determine the excess absolute risk of secondary malignancies. Calculated values were compared with tumor registry reports of excess secondary malignancies among testicular cancer survivors. RESULTS: Photon and proton plans provided comparable target volume coverage. Proton plans delivered significantly lower mean doses to all examined normal tissues, except for the kidneys. The greatest absolute reduction in mean dose was observed for the stomach (119 cGy for proton plans vs. 768 cGy for photon plans; p < 0.0001). Significantly more excess secondary cancers per 10,000 patients/year were predicted for photon radiation than for proton radiation to the stomach (4.11; 95% confidence interval [CI], 3.22-5.01), large bowel (0.81; 95% CI, 0.39-1.01), and bladder (0.03; 95% CI, 0.01-0.58), while no difference was demonstrated for radiation to the pancreas (0.02; 95% CI, -0.01-0.06). CONCLUSIONS: For patients with stage I seminoma, proton radiation therapy reduced the predicted secondary cancer risk compared with photon therapy. We predict a reduction of one additional secondary cancer for every 50 patients with a life expectancy of 40 years from the time of radiation treatment with protons instead of photons. Proton radiation therapy also allowed significant sparing of most critical structures examined and warrants further study for patients with seminoma, to decrease radiation-induced toxicity.

Low rate of thoracic toxicity in palliative paraspinal single-fraction stereotactic body radiation therapy.

BACKGROUND: There has been an increase in the utilization of single-fraction stereotactic body radiation therapy (SBRT) to treat thoracic structures, but there have been few reports describing toxicity outcomes with this treatment. METHODS: We evaluated 119 sites (114 patients) with no prior history of thoracic radiation were treated from 10/1/2003 to 10/27/2008 with single-fraction SBRT to thoracic structures. The median dose to the gross tumor volume was 2400 cGy (range 1800-2400 cGy), as was the median dose to the planning target volume (range 1600-2400 cGy). A detailed review of thoracic toxicities was performed to include pneumonitis or Grade 2 or higher esophageal and bronchial toxicity. In addition, we retrospectively contoured the esophagus and bronchus of 48 patients treated in 2004-2005, prior to the establishment of dose constraints to determine the range of doses that these structures received. RESULTS: Of the contoured patients, the median dose to the hottest 1cc (D1cc) of the esophagus was 1250 cGy (range 158-2572 cGy). The median bronchial D1cc was 1101 cGy (range 260-2211 cGy). At a median follow-up of 11.6 months, there were seven Grade 2 or higher esophageal toxicities, including one Grade 3 and one Grade 4 toxicities. There were two bronchial toxicities, one Grade 2 and one Grade 3. There were no cases of pneumonitis. CONCLUSIONS: High-dose single-fraction SBRT is well tolerated to the thoracic region, with most patients tolerating high doses to central structures without significant toxicity.

Advances in nasopharyngeal carcinoma.

PURPOSE OF REVIEW: Intergroup 0099 established the role of concurrent chemotherapy with radiation therapy in the treatment of locally advanced nasopharyngeal carcinoma, but its reproducibility was unclear and chemotherapy compliance was poor. Multiple concurrent chemoradiation phase III trials were initiated in response to the Intergroup trial, and technologic advances in radiotherapy were explored to improve the therapeutic ratio. This review highlights recent advances in the management of nasopharyngeal carcinoma as a result of these endeavors. RECENT FINDINGS: Five randomized phase III trials confirmed the benefit of concurrent chemoradiation over radiation therapy alone, firmly establishing concurrent chemoradiation as the standard of care in locally advanced nasopharyngeal carcinoma. Each of these studies used conventional radiation therapy and noted an increase in toxicity over radiation therapy alone. Intensity-modulated radiation therapy is an advanced form of three-dimensional conformal radiotherapy which allows delivery of high doses of radiation to the tumor while sparing adjacent normal tissues, leading to improved local control and decreased radiation therapy-induced toxicities. Distant metastasis remains a significant problem despite intensity-modulated radiation therapy. Taxane-based induction chemotherapy seems promising in phase II studies. Targeted therapies remain a major area of interest and require further investigation. SUMMARY: Cisplatin-based concurrent chemoradiation followed by adjuvant chemotherapy is the standard of care for locally advanced nasopharyngeal carcinoma. Intensity-modulated radiation therapy has undergone a rapid evolution and is replacing conventional radiation therapy in many institutions. A multidisciplinary effort is under way to explore more effective systemic therapy to improve the distant metastasis free rates.