Effect of respiratory gating on reducing lung motion artifacts in PET imaging of lung cancer.

Positron emission tomography (PET) has shown an increase in both sensitivity and specificity over computed tomography (CT) in lung cancer. However, motion artifacts in the 18F fluorodioxydoglucose (FDG) PET images caused by respiration persists to be an important factor in degrading PET image quality and quantification. Motion artifacts lead to two major effects: First, it affects the accuracy of quantitation, producing a reduction of the measured standard uptake value (SUV). Second, the apparent lesion volume is overestimated. Both impact upon the usage of PET images for radiation treatment planning. The first affects the visibility, or contrast, of the lesion. The second results in an increase in the planning target volume, and consequently a greater radiation dose to the normal tissues. One way to compensate for this effect is by applying a multiple-frame capture technique. The PET data are then acquired in synchronization with the respiratory motion. Reduction in smearing due to gating was investigated in both phantoms and patient studies. Phantom studies showed a dependence of the reduction in smearing on the lesion size, the motion amplitude, and the number of bins used for data acquisition. These studies also showed an improvement in the target-to-background ratio, and a more accurate measurement of the SUV. When applied to one patient, respiratory gating showed a 28% reduction in the total lesion volume, and a 56.5% increase in the SUV. This study was conducted as a proof of principle that a gating technique can effectively reduce motion artifacts in PET image acquisition.

Fluoroscopic evaluation of diaphragmatic motion reduction with a respiratory gated radiotherapy system.

We report on initial patient studies to evaluate the performance of a commercial respiratory gating radiotherapy system. The system uses a breathing monitor, consisting of a video camera and passive infrared reflective markers placed on the patient's thorax, to synchronize radiation from a linear accelerator with the patient's breathing cycle. Six patients receiving treatment for lung cancer participated in a study of system characteristics during treatment simulation with fluoroscopy. Breathing synchronized fluoroscopy was performed initially without instruction, followed by fluoroscopy with recorded verbal instruction (i.e., when to inhale and exhale) with the tempo matched to the patient's normal breathing period. Patients tended to inhale more consistently when given instruction, as assessed by an external marker movement. This resulted in smaller variation in expiration and inspiration marker positions relative to total excursion, thereby permitting more precise gating tolerances at those parts of the breathing cycle. Breathing instruction also reduced the fraction of session times having irregular breathing as measured by the system software, thereby potentially increasing the accelerator duty factor and decreasing treatment times. Fluoroscopy studies showed external monitor movement to correlate well with that of the diaphragm in four patients, whereas time delays of up to 0.7 s in diaphragm movement were observed in two patients with impaired lung function. From fluoroscopic observations, average patient diaphragm excursion was reduced from 1.4 cm (range 0.7-2.1 cm) without gating and without breathing instruction, to 0.3 cm (range 0.2-0.5 cm) with instruction and with gating tolerances set for treatment at expiration for 25% of the breathing cycle. Patients expressed no difficulty with following instruction for the duration of a session. We conclude that the external monitor accurately predicts internal respiratory motion in most cases; however, it may be important to check with fluoroscopy for possible time delays in patients with impaired lung function. Furthermore, we observe that verbal instruction can improve breathing regularity, thus improving the performance of gated treatments with this system.

Elective nodal irradiation in the treatment of non-small-cell lung cancer with three-dimensional conformal radiation therapy.

PURPOSE: Dose escalation using three-dimensional conformal radiation therapy (3D-CRT) has been investigated as a means to improve local control. However, with higher doses, the risk of toxicity increases. Early in our experience, we ceased treating elective nodal areas (lymph node stations without evidence of tumor involvement) in an effort to decrease toxicity while treating the gross tumor to higher doses. This report measures the rate of regional failure without elective radiation therapy to uninvolved lymph nodes. METHODS AND MATERIALS: A total of 171 patients with non-small-cell lung cancer treated with 3D-CRT at Memorial Sloan-Kettering Cancer Center between 1991 and 1998 were reviewed. Only lymph node regions initially involved with tumor either by biopsy (55%) or radiographic criteria (node > or =15 mm in the short axis on CT) were included in the clinical target volume. Elective nodal failure was defined as a recurrence in an initially uninvolved lymph node in the absence of local failure. RESULTS: Only 11 patients (6.4%) with elective nodal failure were identified. With a median follow-up of 21 months in survivors, the 2-year actuarial rates of elective nodal control and primary tumor control were 91% and 38%, respectively. In patients who were locally controlled, the 2-year rate of elective nodal control was 85%. The median time to elective nodal failure was 4 months (range, 1-19 months). Most patients failed in multiple lymph node regions simultaneously. CONCLUSION: Local control remains one of the biggest challenges in the treatment of non-small-cell lung cancer. Most patients in our series developed local failure within 2 years of radiation therapy. The omission of elective nodal treatment did not cause a significant amount of failure in lymph node regions not included in the clinical target volume. Therefore, we will continue our policy of treating mediastinal lymph node regions only if they are clinically involved with tumor.

Three-dimensional conformal radiation therapy (3D-CRT) for early-stage non-small-cell lung cancer.

The standard treatment for early-stage non-small-cell lung cancer is surgical resection. However, many patients are inoperable due to medical comorbidities. Thirty-two medically inoperable patients with early-stage non-small-cell lung cancer were treated with 3-dimensional conformal radiation therapy between January 1991 and December 2000. The median dose was 70.2 Gy, and the median follow-up time in survivors was 30 months. The 2-year actuarial local control, overall survival, and cancer-specific survival rates were 43%, 54%, and 57%, respectively. The 5-year actuarial local control, overall survival, and cancer-specific survival rates were 43%, 33%, and 39%, respectively. This report suggests that local control is improved with high-dose conformal radiation therapy when compared to other institutions' retrospective experiences.

Technical aspects of the deep inspiration breath-hold technique in the treatment of thoracic cancer.

PURPOSE: The goal of this paper is to describe our initial experience with the deep inspiration breath-hold (DIBH) technique in conformal treatment of non-small-cell lung cancer with particular emphasis on the technical aspects required for implementation. METHODS AND MATERIALS: In the DIBH technique, the patient is verbally coached through a modified slow vital capacity maneuver and brought to a reproducible deep inspiration breath-hold level. The goal is to immobilize the tumor and to expand normal lung out of the high-dose region. A physicist or therapist monitors and records patient breathing during simulation, verification, and treatment using a spirometer with a custom computer interface. Examination of internal anatomy during fluoroscopy over multiple breath holds establishes the reproducibility of the DIBH maneuver for each patient. A reference free-breathing CT scan and DIBH planning scan are obtained. To provide an estimate of tumor motion during normal tidal breathing, additional scan sets are obtained at end inspiration and end expiration. These are also used to set the spirometer action levels for treatment. Patient lung inflation is independently verified over the course of treatment by comparing the distance from the isocenter to the diaphragm measured from the DIBH digitally reconstructed radiographs to the distance measured on the portal films. Patient breathing traces obtained during treatment were examined retrospectively to assess the reproducibility of the technique. RESULTS: Data from the first 7 patients, encompassing over 250 treatments, were analyzed. The inferred displacement of the centroid of gross tumor volume from its position in the planning scan, as calculated from the spirometer records in over 350 breath holds was 0.02 +/- 0.14 cm (mean and standard deviation). These data are consistent with the displacements of the diaphragm (-0.1 +/- 0.4 cm; range, from -1.2 to 1.1 cm) relative to the isocenter, as measured on the (92) portal films. The latter measurements include the patient setup error. The patient averaged displacement of the tumor during free breathing, determined from the tumor displacement between end inspiration and end expiration, was 0.8 +/- 0.5 cm in both the superior-inferior and anterior-posterior directions and 0.1 cm (+/- 0.1 cm) medial-laterally. CONCLUSION: Treatment of patients with the DIBH technique is feasible in a clinical setting. With this technique, consistent lung inflation levels are achieved in patients, as judged by both spirometry and verification films. Breathing-induced tumor motion is significantly reduced using DIBH compared to free breathing, enabling better target coverage.

Quantitative effect of combined chemotherapy and fractionated radiotherapy on the incidence of radiation-induced lung damage: a prospective clinical study.

PURPOSE: The objective of this work was to assess the incidence of radiological changes compatible with radiation-induced lung damage as determined by computed tomography (CT), and subsequently calculate the dose effect factors (DEF) for specified chemotherapeutic regimens. METHODS AND MATERIALS: A prospective, clinical study was conducted to determine the response of normal lung tissue to combined chemotherapy and radiotherapy. Radiation treatments were administered once daily, 5 days-per-week. Six clinical protocols were evaluated: ABVD (adriamycin, bleomycin, vincristine, and DTIC) followed by 35 Gy in 20 fractions; MOPP (nitrogen mustard, vincristine, procarbazine, and prednisone) followed by 35 Gy in 20; MOPP/ABVD followed by 35 Gy in 20; CAV (cyclophosphamide, adriamycin, and vincristine) followed by 25 Gy in 10; and 5-FU (5-fluorouracil) concurrent with either 50-52 Gy in 20-21 or 30-36 Gy in 10-15 fractions. CT examinations were taken before and at predetermined intervals following radiotherapy. CT evidence for the development of radiation-induced damage was defined as an increase in lung density within the irradiated volume. The radiation dose to lung was calculated using a CT-based algorithm to account for tissue inhomogeneities. Different fractionation schedules were converted using two isoeffect models, the estimated single dose (ED) and the normalized total dose (NTD). RESULTS: A total of 102 patients were entered and 70 completed the study. Forty-two patients developed CT changes compatible with lung damage. The actuarial incidence of radiological pneumonitis was 71% for the ABVD, 49% for MOPP, 52% for MOPP/ABVD, 67% for CAV, 73% for 5-FU radical, and 58% for 5-FU palliative protocols. Depending on the isoeffect model selected and the method of analysis, the DEF was 1.11-1.14 for the ABVD, 0.96-0.97 for the MOPP, 0.96-1.02 for the MOPP/ABVD, 1.03-1.10 for the CAV, 0.74-0.79 for the 5-FU radical, and 0.94 for the 5-FU palliative protocols. CONCLUSION: Quantitative dose effect factors (DEF) were measured by comparing the incidences of CT-observed lung damage in patients receiving chemotherapy and radiotherapy to those receiving radiotherapy alone. The addition of ABVD or CAV appeared to reduce the tolerance of lung to radiation.