Aaron M. Allen

Dose to Larynx Predicts for Swallowing Complications After Intensity-Modulated Radiotherapy

PURPOSE To evaluate early swallowing after intensity-modulated radiotherapy for head and neck squamous cell carcinoma and determine factors correlating with aspiration and/or stricture. METHODS AND MATERIALS Consecutive patients treated with intensity-modulated radiotherapy with or without chemotherapy between September 2004 and August 2006 at the Dana Farber Cancer Institute/Brigham and Womens Hospital were evaluated with institutional review board approval. Patients underwent swallowing evaluation after completion of therapy; including video swallow studies. The clinical- and treatment-related variables were examined for correlation with aspiration or strictures, as well as doses to the larynx, pharyngeal constrictor muscles, and cervical esophagus. The correlation was assessed with logistic regression analysis. RESULTS A total of 96 patients were evaluated. Their median age was 55 years, and 79 (82%) were men. The primary site of cancer was the oropharynx in 43, hypopharynx/larynx in 17, oral cavity in 13, nasopharynx in 11, maxillary sinus in 2, and unknown primary in 10. Of the 96 patients, 85% underwent definitive RT and 15% postoperative RT. Also, 28 patients underwent induction chemotherapy followed by concurrent chemotherapy, 59 received concurrent chemotherapy, and 9 patients underwent RT alone. The median follow-up was 10 months. Of the 96 patients, 31 (32%) had clinically significant aspiration and 36 (37%) developed a stricture. The radiation dose-volume metrics, including the volume of the larynx receiving >or=50 Gy (p = 0.04 and p = 0.03, respectively) and volume of the inferior constrictor receiving >or=50 Gy (p = 0.05 and p = 0.02, respectively) were significantly associated with both aspiration and stricture. The mean larynx dose correlated with aspiration (p = 0.003). Smoking history was the only clinical factor to correlate with stricture (p = 0.05) but not aspiration. CONCLUSION Aspiration and stricture are common side effects after intensity-modulated radiotherapy for head-and-neck squamous cell carcinoma. The dose given to the larynx and inferior constrictors correlated with these side effects.

RADIATION DOSE-VOLUME EFFECTS IN THE LARYNX AND PHARYNX

The dose-volume outcome data for RT-associated laryngeal edema, laryngeal dysfunction, and dysphagia, have only recently been addressed, and are summarized. For late dysphagia, a major issue is accurate definition and uncertainty of the relevant anatomical structures. These and other issues are discussed.

Clinical Utility of 4D FDG-PET/CT Scans in Radiation Treatment Planning

PURPOSE The potential role of four-dimensional (4D) positron emission tomography (PET)/computed tomography (CT) in radiation treatment planning, relative to standard three-dimensional (3D) PET/CT, was examined. METHODS AND MATERIALS Ten patients with non-small-cell lung cancer had sequential 3D and 4D [(18)F]fluorodeoxyglucose PET/CT scans in the treatment position prior to radiation therapy. The gross tumor volume and involved lymph nodes were contoured on the PET scan by use of three different techniques: manual contouring by an experienced radiation oncologist using a predetermined protocol; a technique with a constant threshold of standardized uptake value (SUV) greater than 2.5; and an automatic segmentation technique. For each technique, the tumor volume was defined on the 3D scan (VOL3D) and on the 4D scan (VOL4D) by combining the volume defined on each of the five breathing phases individually. The range of tumor motion and the location of each lesion were also recorded, and their influence on the differences observed between VOL3D and VOL4D was investigated. RESULTS We identified and analyzed 22 distinct lesions, including 9 primary tumors and 13 mediastinal lymph nodes. Mean VOL4D was larger than mean VOL3D with all three techniques, and the difference was statistically significant (p < 0.01). The range of tumor motion and the location of the tumor affected the magnitude of the difference. For one case, all three tumor definition techniques identified volume of moderate uptake of approximately 1 mL in the hilar region on the 4D scan (SUV maximum, 3.3) but not on the 3D scan (SUV maximum, 2.3). CONCLUSIONS In comparison to 3D PET, 4D PET may better define the full physiologic extent of moving tumors and improve radiation treatment planning for lung tumors. In addition, reduction of blurring from free-breathing images may reveal additional information regarding regional disease.

Efficacy and Toxicity of Reirradiation Using Intensity-Modulated Radiotherapy for Recurrent or Second Primary Head and Neck Cancer

Patients with locally recurrent squamous cell cancer of the head and neck (SCCHN) are reported to have a poor prognosis and limited therapeutic options. Optimal management is selectively applied and morbid. Both surgical resection and chemoradiotherapy are reported to result in median survivals of approximately 12 months. Intensity‐modulated radiotherapy (IMRT) is a highly conformal approach for delivering RT. This study reported the experience of the Dana‐Farber Cancer Institute (DFCI) with IMRT‐based chemoradiotherapy with or without surgery for locally recurrent SCCHN.

Randomized phase 2 study of concomitant chemoradiotherapy using weekly carboplatin/paclitaxel with or without daily subcutaneous amifostine in patients with locally advanced head and neck cancer.

A randomized phase 2 study was performed to investigate the efficacy/toxicity of combining concomitant boost radiation and weekly carboplatin/paclitaxel with or without amifostine in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN).

Phase I dose-finding study of paclitaxel with panitumumab, carboplatin and intensity-modulated radiotherapy in patients with locally advanced squamous cell cancer of the head and neck

BACKGROUND Panitumumab has the potential to improve the therapeutic ratio of concurrent chemoradiotherapy for squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS This phase I dose-finding study investigated escalating doses of paclitaxel (Taxol) given concurrently with panitumumab, carboplatin and intensity-modulated radiotherapy (IMRT) for stage III-IVB SCCHN. Untreated patients with oral cavity, oropharynx, larynx, hypopharynx or unknown primaries were eligible. Additional eligibility criteria included measurable disease, good performance status and no contraindication to therapy. Patients received weekly fixed doses of panitumumab and carboplatin plus escalating doses of paclitaxel with IMRT. RESULTS Nineteen patients were enrolled on to two dose levels (DLs): weekly paclitaxel 15 mg/m(2) (n = 3) and 30 mg/m(2) (n = 16). One dose-limiting toxicity occurred in DL 2, which was declared the maximum tolerated dose. All patients experienced mucositis, primarily grade 3 or more. Oral pain, xerostomia, dysphagia, weight loss, dermatitis, nausea and acneiform rash were frequent. All patients had partial response according to RECIST, whereas the overall complete clinical response rate was 95%. At median follow-up of 21 months, 18 of 19 patients (95%) remained disease free. CONCLUSIONS Panitumumab, carboplatin, paclitaxel and IMRT are well tolerated and appear highly active in the treatment of SCCHN. Further study of this regimen in SCCHN is warranted.

Evaluation of the interplay effect when using RapidArc to treat targets moving in the craniocaudal or right-left direction

PURPOSE We have investigated the dosimetric errors caused by the interplay between the motions of the LINAC and the tumor during the delivery of a volume modulated arc therapy treatment. This includes the development of an IMRT QA technique, applied here to evaluate RapidArc plans of varying complexity. METHODS An IMRT QA technique was developed, which involves taking a movie of the delivered dose (0.2 s frames) using a 2D ion chamber array. Each frame of the movie is then moved according to a respiratory trace and the cumulative dose calculated. The advantage of this approach is that the impact of turning the beam on at different points in the respiratory trace, and of different types of motion, can be evaluated using data from a single irradiation. We evaluated this technique by comparing with the results when we actually moved the phantom during irradiation. RapidArc plans were created to treat a 62 cc spherical tumor in a lung phantom (16 plans) and a 454 cc irregular tumor in an actual patient (five plans). The complexity of each field was controlled by adjusting the MU (312-966 MU). Each plan was delivered to a phantom, and a movie of the delivered dose taken using a 2D ion chamber array. Patient motion was modeled by shifting each dose frame according to a respiratory trace, starting the motion at different phases. The expected dose distribution was calculated by blurring the static dose distribution with the target motion. The dose error due to the interplay effect was then calculated by comparing the delivered dose with the expected dose distribution. Peak-to-peak motion of 0.5, 1.0, and 2.0 cm in the craniocaudal and right-left directions, with target periods of 3 and 5 s, were evaluated for each plan (252 different target motion/plan combinations). RESULTS The daily dose error due to the interplay effect was less than 10% for 98.4% of all pixels in the target for all plans investigated. The percentage of pixels for which the daily dose error could be larger than 5% increased with increasing plan complexity (field MU), but was less than 15% for all plans if the motion was 1 cm or less. For 2 cm motion, the dose error could be larger than 5% for 40% of pixels, but was less than 5% for more than 80% of pixels for MU < 550, and was less than 10% for 99% of all pixels. The interplay effect was smaller for 3 s periods than for 5 s periods. CONCLUSIONS The interplay between the motions of the LINAC and the target can result in an error in the delivered dose. This effect increases with plan complexity, and with target magnitude and period. It may average out after many fractions.

Tumor Volume Is a Prognostic Factor in Non–Small-Cell Lung Cancer Treated With Chemoradiotherapy

PURPOSE To investigate whether primary tumor and nodal volumes defined on radiotherapy planning scans are correlated with outcome (survival and recurrence) after combined-modality treatment. METHODS AND MATERIALS A retrospective review of patients with Stage III non-small-cell lung cancer treated with chemoradiation at Brigham and Womens Hospital/Dana-Farber Cancer Institute from 2000 to 2006 was performed. Tumor and nodal volume measurements, as computed by Eclipse (Varian, Palo Alto, CA), were used as independent variables, along with existing clinical factors, in univariate and multivariate analyses for association with outcomes. RESULTS For patients treated with definitive chemoradiotherapy, both nodal volume (hazard ratio [HR], 1.09; p < 0.01) and tumor volume (HR, 1.03; p < 0.01) were associated with overall survival on multivariate analysis. Both nodal volume (HR, 1.10; p < 0.01) and tumor volume (HR, 1.04; p < 0.01) were also associated with local control but not distant metastases. CONCLUSIONS In addition to traditional surgical staging variables, disease burden, measured by primary tumor and nodal metastases volume, provides information that may be helpful in determining prognosis and identifying groups of patients for which more aggressive local therapy is warranted.

Pneumonectomy after chemoradiation: the Dana-Farber Cancer Institute/Brigham and Women's Hospital experience.

The current study was conducted to examine the outcomes of pneumonectomy after induction chemoradiotherapy in patients with locally advanced nonsmall cell lung cancer (NSCLC).

Experimental evaluation of the accuracy of skin dose calculation for a commercial treatment planning system

The present work uses the Eclipse treatment planning system (TPS) to investigate the accuracy of skin dose calculations. Micro‐MOSFETs (metal oxide semiconductor field effect transistors) were used to measure skin dose for a range of irradiation conditions (open fields, physical wedges, dynamic wedges, various source‐to‐surface distances) for 6‐MV and 10‐MV beams, and the results were compared with the calculated mean dose to a “skin” structure 2 mm thick for semi‐cylindrical phantoms (representative of a neck or breast). Agreement between the calculated and measured skin dose values was better than ±20% for 95% of all measured points (6‐MV and 10‐MV X‐ray spectra alike). For a fixed geometry, the TPS correctly calculated relative changes in dose, showing that minimization of skin dose in intensity‐modulated radiation therapy will be effective in Eclipse. PACS numbers: 87.53.Bn, 87.53.Dq, 87.66.Pm, 87.66.Xa