Decision Regret among Patients with Early-stage Lung Cancer Undergoing Radiation Therapy or Surgical Resection.

AIMS: Clinical equipoise exists regarding early-stage lung cancer treatment among patients as trials comparing stereotactic body radiation therapy (SBRT) and surgical resection are unavailable. Given the potential differences in treatment effectiveness and side-effects, we sought to determine the associations between treatment type, decision regret and depression. MATERIALS AND METHODS: A multicentre, prospective study of patients with stage IA-IIA non-small cell lung cancer (NSCLC) with planned treatment with SBRT or surgical resection was conducted. Decision regret and depression were measured using the Decision Regret Scale (DRS) and Patient Health Questionnaire-4 (PHQ-4) at 3, 6 and 12 months post-treatment, respectively. Mixed linear regression modelling examined associations between treatment and decision regret adjusting for patient sociodemographics. RESULTS: Among 211 study participants with early-stage lung cancer, 128 (61%) patients received SBRT and 83 (39%) received surgical resection. The mean age was 73 years (standard deviation = 8); 57% were female; 79% were White non-Hispanic. In the entire cohort at 3 months post-treatment, 72 (34%) and 57 (27%) patients had mild and severe decision regret, respectively. Among patients who received SBRT or surgery, 71% and 46% of patients experienced at least mild decision regret at 3 months, respectively. DRS scores increased at 6 months and decreased slightly at 12 months of follow-up in both groups. Higher DRS scores were associated with SBRT treatment (adjusted mean difference = 4.18, 95% confidence interval 0.82 to 7.54) and depression (adjusted mean difference = 3.49, 95% confidence interval 0.52 to 6.47). Neither patient satisfaction with their provider nor decision-making role concordance was associated with DRS scores. CONCLUSIONS: Most early-stage lung cancer patients experienced at least mild decision regret, which was associated with SBRT treatment and depression symptoms. Findings suggest patients with early-stage lung cancer may not be receiving optimal treatment decision-making support. Therefore, opportunities for improved patient-clinician communication probably exist.

Radiation therapy for malignant pleural mesothelioma.

The treatment of malignant pleural mesothelioma with radiation has always been a technical challenge. For many years, conventional radiation therapy was delivered after extrapleural pneumonectomy with acceptable results. Novel radiation treatment techniques, such as intensity modulated radiation therapy (IMRT) were introduced, but the early experience with IMRT demonstrated troubling toxicity. Recent reports from institutions have demonstrated that with greater experience, IMRT, both in the setting of extrapleural pneumonectomy or pleurectomy, can be delivered safely. A recent study, SAKK 17/04, questions the role of using radiation after extrapleural pneumonectomy.

A study of respiration-correlated cone-beam CT scans to correct target positioning errors in radiotherapy of thoracic cancer.

PURPOSE: There is increasingly widespread usage of cone-beam CT (CBCT) for guiding radiation treatment in advanced-stage lung tumors, but difficulties associated with daily CBCT in conventionally fractionated treatments include imaging dose to the patient, increased workload and longer treatment times. Respiration-correlated cone-beam CT (RC-CBCT) can improve localization accuracy in mobile lung tumors, but further increases the time and workload for conventionally fractionated treatments. This study investigates whether RC-CBCT-guided correction of systematic tumor deviations in standard fractionated lung tumor radiation treatments is more effective than 2D image-based correction of skeletal deviations alone. A second study goal compares respiration-correlated vs respiration-averaged images for determining tumor deviations. METHODS: Eleven stage II-IV nonsmall cell lung cancer patients are enrolled in an IRB-approved prospective off-line protocol using RC-CBCT guidance to correct for systematic errors in GTV position. Patients receive a respiration-correlated planning CT (RCCT) at simulation, daily kilovoltage RC-CBCT scans during the first week of treatment and weekly scans thereafter. Four types of correction methods are compared: (1) systematic error in gross tumor volume (GTV) position, (2) systematic error in skeletal anatomy, (3) daily skeletal corrections, and (4) weekly skeletal corrections. The comparison is in terms of weighted average of the residual GTV deviations measured from the RC-CBCT scans and representing the estimated residual deviation over the treatment course. In the second study goal, GTV deviations computed from matching RCCT and RC-CBCT are compared to deviations computed from matching respiration-averaged images consisting of a CBCT reconstructed using all projections and an average-intensity-projection CT computed from the RCCT. RESULTS: Of the eleven patients in the GTV-based systematic correction protocol, two required no correction, seven required a single correction, one required two corrections, and one required three corrections. Mean residual GTV deviation (3D distance) following GTV-based systematic correction (mean ± 1 standard deviation 4.8 ± 1.5 mm) is significantly lower than for systematic skeletal-based (6.5 ± 2.9 mm, p = 0.015), and weekly skeletal-based correction (7.2 ± 3.0 mm, p = 0.001), but is not significantly lower than daily skeletal-based correction (5.4 ± 2.6 mm, p = 0.34). In two cases, first-day CBCT images reveal tumor changes-one showing tumor growth, the other showing large tumor displacement-that are not readily observed in radiographs. Differences in computed GTV deviations between respiration-correlated and respiration-averaged images are 0.2 ± 1.8 mm in the superior-inferior direction and are of similar magnitude in the other directions. CONCLUSIONS: An off-line protocol to correct GTV-based systematic error in locally advanced lung tumor cases can be effective at reducing tumor deviations, although the findings need confirmation with larger patient statistics. In some cases, a single cone-beam CT can be useful for assessing tumor changes early in treatment, if more than a few days elapse between simulation and the start of treatment. Tumor deviations measured with respiration-averaged CT and CBCT images are consistent with those measured with respiration-correlated images; the respiration-averaged method is more easily implemented in the clinic.

SU-E-T-315: Planning and Verification of CT-Based HDR Intraluminal Brachytherapy Treatment for Malignant Obstructive Jaundice.

PURPOSE: To present our experience using CT to plan and verify intraluminal HDR treatment for a patient with obstructive jaundice. Due to the obstruction's proximity to the small bowel, along with small bowel adhesions from past surgical history, it was imperative to verify source position relative to the bowel before each treatment. METHODS: Treatment was administered to a total dose of 2000cGy in 5 fractions via a 6F intraluminal catheter inserted into the patient's 14F percutaneous drainage catheter. Graduations on the intraluminal catheter were used to measure the exact length of catheter inserted in to the patient's drainage tube allowing reproducibility. Dummy seeds inserted during CT were identified by iteratively aligning the planning system's 3D reconstruction axis to the catheter at multiple points as it snaked through the liver. Taking in to account the known offset between actual dwell positions and dummy source positions, we determined what dwell positions to activate for planning. CT verification was performed prior to each treatment to insure that the drainage catheter had not moved and that the distance from treatment site to small bowel was adequate. Dummy seeds and anatomical landmarks were identified on the scout image and correlated to the CT. RESULTS: Verification CTs showed remarkable consistency in the day-to-day drainage catheter position. The physician was able to easily identify the small bowel of concern on the CT and determine if a safe distance existed for treatment. CONCLUSIONS: The method outlined in this work provides a safe means by which to treat bile duct obstructions using HDR when critical structures are nearby. We were prepared to make real-time adjustments to our treatment plan to account for significant variation, but found it unnecessary to do so in this particular case.

Phase and amplitude binning for 4D-CT imaging.

We compare the consistency and accuracy of two image binning approaches used in 4D-CT imaging. One approach, phase binning (PB), assigns each breathing cycle 2pi rad, within which the images are grouped. In amplitude binning (AB), the images are assigned bins according to the breathing signal's full amplitude. To quantitate both approaches we used a NEMA NU2-2001 IEC phantom oscillating in the axial direction and at random frequencies and amplitudes, approximately simulating a patient's breathing. 4D-CT images were obtained using a four-slice GE Lightspeed CT scanner operating in cine mode. We define consistency error as a measure of ability to correctly bin over repeated cycles in the same field of view. Average consistency error mue+/-sigmae in PB ranged from 18%+/-20% to 30%+/-35%, while in AB the error ranged from 11%+/-14% to 20%+/-24%. In PB nearly all bins contained sphere slices. AB was more accurate, revealing empty bins where no sphere slices existed. As a proof of principle, we present examples of two non-small cell lung carcinoma patients' 4D-CT lung images binned by both approaches. While AB can lead to gaps in the coronal images, depending on the patient's breathing pattern, PB exhibits no gaps but suffers visible artifacts due to misbinning, yielding images that cover a relatively large amplitude range. AB was more consistent, though often resulted in gaps when no data existed due to patients' breathing pattern. We conclude AB is more accurate than PB. This has important consequences to treatment planning and diagnosis.

Reduction of organ motion effects in IMRT and conformal 3D radiation delivery by using gating and tracking techniques.

Respiration-gated radiotherapy offers a significant potential for improvement in the irradiation of tumour sites affected by respiratory motion such as lung, breast and liver tumours. An increased conformality of irradiation fields leading to decreased complications rates of organs at risk (lung, heart) is expected. Four main strategies are used to reduce respiratory motion effects: integration of respiratory movements into treatment planning, breath-hold techniques, respiratory gating techniques, and tracking techniques. Measurements of respiratory movements can be performed either in a representative sample of the general population, or directly on the patient before irradiation. The measured amplitude could be applied to a geometrical margin or integrated into dosimetry. However, these strategies remain limited for very mobile tumours, in which this approach results in larger irradiated volumes. Reduction of breathing motion can be achieved by using either breath-hold techniques or respiration synchronized gating techniques. Breath-hold can be achieved with active techniques, in which a valve temporarily blocks airflow of the patient, or passive techniques, in which the patient voluntarily breath-holds. Synchronized gating techniques use external devices to predict the phase of the respiration cycle while the patient breaths freely. Another category is tumour tracking, which consists of two major aspects: real-time localization of, and real-time beam adaptation to, a constantly moving tumour. These techniques are presently being investigated in several medical centres worldwide. Although promising, the first results obtained in lung and liver cancer patients require confirmation. This paper describes the most frequently used gating and tracking techniques and the main published clinical reports.

Evaluation of an automated deformable image matching method for quantifying lung motion in respiration-correlated CT images.

We have evaluated an automated registration procedure for predicting tumor and lung deformation based on CT images of the thorax obtained at different respiration phases. The method uses a viscous fluid model of tissue deformation to map voxels from one CT dataset to another. To validate the deformable matching algorithm we used a respiration-correlated CT protocol to acquire images at different phases of the respiratory cycle for six patients with nonsmall cell lung carcinoma. The position and shape of the deformable gross tumor volumes (GTV) at the end-inhale (EI) phase predicted by the algorithm was compared to those drawn by four observers. To minimize interobserver differences, all observers used the contours drawn by a single observer at end-exhale (EE) phase as a guideline to outline GTV contours at EI. The differences between model-predicted and observer-drawn GTV surfaces at EI, as well as differences between structures delineated by observers at EI (interobserver variations) were evaluated using a contour comparison algorithm written for this purpose, which determined the distance between the two surfaces along different directions. The mean and 90% confidence interval for model-predicted versus observer-drawn GTV surface differences over all patients and all directions were 2.6 and 5.1 mm, respectively, whereas the mean and 90% confidence interval for interobserver differences were 2.1 and 3.7 mm. We have also evaluated the algorithm's ability to predict normal tissue deformations by examining the three-dimensional (3-D) vector displacement of 41 landmarks placed by each observer at bronchial and vascular branch points in the lung between the EE and EI image sets (mean and 90% confidence interval displacements of 11.7 and 25.1 mm, respectively). The mean and 90% confidence interval discrepancy between model-predicted and observer-determined landmark displacements over all patients were 2.9 and 7.3 mm, whereas interobserver discrepancies were 2.8 and 6.0 mm. Paired t tests indicate no significant statistical differences between model predicted and observer drawn structures. We conclude that the accuracy of the algorithm to map lung anatomy in CT images at different respiratory phases is comparable to the variability in manual delineation. This method has therefore the potential for predicting and quantifying respiration-induced tumor motion in the lung.

Response to radiation.

Computed tomography (CT) has traditionally been the standard radiographic modality for diagnosing and monitoring non-small cell; lung cancer (NSCLC) after treatment. Given the limitations of CT, the utility of 18F-fluoro-2-deoxy-glucose positron emission tomography (FDG-PET) has been investigated for the management of NSCLC, with promising findings. Its adjunctive role with CT in diagnosing and staging disease is well established. FDG-PET also has been found to be a valuable tool for radiation treatment planning because it improves the precision of lesion definition. More recently, its value for determining clinical response both during and after treatment has been explored. This review highlights the various applications of FDG-PET in the diagnosis and management of NSCLC as corroborated by clinical data, with considerations of future directions.

Quantitation of respiratory motion during 4D-PET/CT acquisition.

We report on the variability of the respiratory motion during 4D-PET/CT acquisition. The respiratory motion for five lung cancer patients was monitored by tracking external markers placed on the abdomen. CT data were acquired over an entire respiratory cycle at each couch position. The x-ray tube status was recorded by the tracking system, for retrospective sorting of the CT data as a function of respiration phase. Each respiratory cycle was sampled in ten equal bins. 4D-PET data were acquired in gated mode, where each breathing cycle was divided into ten 500 ms bins. For both CT and PET acquisition, patients received audio prompting to regularize breathing. The 4D-CT and 4D-PET data were then correlated according to their respiratory phases. The respiratory periods, and average amplitude within each phase bin, acquired in both modality sessions were then analyzed. The average respiratory motion period during 4D-CT was within 18% from that in the 4D-PET sessions. This would reflect up to 1.8% fluctuation in the duration of each 4D-CT bin. This small uncertainty enabled good correlation between CT and PET data, on a phase-to-phase basis. Comparison of the average-amplitude within the respiration trace, between 4D-CT and 4D- PET, on a bin-by-bin basis show a maximum deviation of approximately 15%. This study has proved the feasibility of performing 4D-PET/CT acquisition. Respiratory motion was in most cases consistent between PET and CT sessions, thereby improving both the attenuation correction of PET images, and co-registration of PET and CT images. On the other hand, in two patients, there was an increased partial irregularity in their breathing motion, which would prevent accurately correlating the corresponding PET and CT images.

Four-dimensional (4D) PET/CT imaging of the thorax.

We have reported in our previous studies on the methodology, and feasibility of 4D-PET (Gated PET) acquisition, to reduce respiratory motion artifact in PET imaging of the thorax. In this study, we expand our investigation to address the problem of respiration motion in PET/CT imaging. The respiratory motion of four lung cancer patients were monitored by tracking external markers placed on the thorax. A 4D-CT acquisition was performed using a "step-and-shoot" technique, in which computed tomography (CT) projection data were acquired over a complete respiratory cycle at each couch position. The period of each CT acquisition segment was time stamped with an "x-ray ON" signal, which was recorded by the tracking system. 4D-CT data were then sorted into 10 groups, according to their corresponding phase of the breathing cycle. 4D-PET data were acquired in the gated mode, where each breathing cycle was divided into ten 0.5 s bins. For both CT and PET acquisitions, patients received audio prompting to regularize breathing. The 4D-CT and 4D-PET data were then correlated according to respiratory phase. The effect of 4D acquisition on improving the co-registration of PET and CT images, reducing motion smearing, and consequently increase the quantitation of the SUV, were investigated. Also, quantitation of the tumor motions in PET, and CT, were studied and compared. 4D-PET with matching phase 4D-CTAC showed an improved accuracy in PET-CT image co-registration of up to 41%, compared to measurements from 4D-PET with clinical-CTAC. Gating PET data in correlation with respiratory motion reduced motion-induced smearing, thereby decreasing the observed tumor volume, by as much as 43%. 4D-PET lesions volumes showed a maximum deviation of 19% between clinical CT and phase- matched 4D-CT attenuation corrected PET images. In CT, 4D acquisition resulted in increasing the tumor volume in two patients by up to 79%, and decreasing it in the other two by up to 35%. Consequently, these corrections have yielded an increase in the measured SUV by up to 16% over the clinical measured SUV, and 36% over SUV's measured in 4D-PET with clinical-CT Attenuation Correction (CTAC) SUV's. Quantitation of the maximum tumor motion amplitude, using 4D-PET and 4D-CT, showed up to 30% discrepancy between the two modalities. We have shown that 4D PET/CT is clinically a feasible method, to correct for respiratory motion artifacts in PET/CT imaging of the thorax. 4D PET/CT acquisition can reduce smearing, improve the accuracy in PET-CT co-registration, and increase the measured SUV. This should result in an improved tumor assessment for patients with lung malignancies.

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.

Evaluation of respiratory movement during gated radiotherapy using film and electronic portal imaging.

PURPOSE: To evaluate the effectiveness of a commercial system(1) in reducing respiration-induced treatment uncertainty by gating the radiation delivery. METHODS AND MATERIALS: The gating system considered here measures respiration from the position of a reflective marker on the patient's chest. Respiration-triggered planning CT scans were obtained for 8 patients (4 lung, 4 liver) at the intended phase of respiration (6 at end expiration and 2 at end inspiration). In addition, fluoroscopic movies were recorded simultaneously with the respiratory waveform. During the treatment sessions, gated localization films were used to measure the position of the diaphragm relative to the vertebral bodies, which was compared to the reference digitally reconstructed radiograph derived from the respiration-triggered planning CT. Variability was quantified by the standard deviation about the mean position. We also assessed the interfraction variability of soft tissue structures during gated treatment in 2 patients using an amorphous silicon electronic portal imaging device. RESULTS: The gated localization films revealed an interfraction patient-averaged diaphragm variability of 2.8 +/- 1.0 mm (error bars indicate standard deviation in the patient population). The fluoroscopic data yielded a patient-averaged intrafraction diaphragm variability of 2.6 +/- 1.7 mm. With no gating, this intrafraction excursion became 6.9 +/- 2.1 mm. In gated localization films, the patient-averaged mean displacement of the diaphragm from the planning position was 0.0 +/- 3.9 mm. However, in 4 of the 8 patients, the mean (over localization films) displacement was >4 mm, indicating a systematic displacement in treatment position from the planned one. The position of soft tissue features observed in portal images during gated treatments over several fractions showed a mean variability between 2.6 and 5.7 mm. The intrafraction variability, however, was between 0.6 and 1.4 mm, indicating that most of the variability was due to patient setup errors rather than to respiratory motion. CONCLUSIONS: The gating system evaluated here reduces the intra- and interfraction variability of anatomy due to respiratory motion. However, systematic displacements were observed in some cases between the location of an anatomic feature at simulation and its location during treatment. Frequent monitoring is advisable with film or portal imaging.

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.

A phase II trial of surgical resection and adjuvant high-dose hemithoracic radiation for malignant pleural mesothelioma.

BACKGROUND: Surgical resection of malignant pleural mesothelioma is reported to have up to an 80% rate of local recurrence. We performed a phase II trial of high-dose hemithoracic radiation after complete resection to determine feasibility and to estimate rates of local recurrence and survival. METHODS: Patients were eligible if they had a resectable tumor, as determined by computed tomographic scanning, and adequate cardiopulmonary function for extrapleural pneumonectomy or pleurectomy/decortication. After complete resection, patients received hemithoracic radiation (54 Gy) and then were followed up with serial computed tomographic scanning. RESULTS: From 1995 to 1998, 88 patients (73 men and 15 women; median age, 62.5 years) were entered into the study. The operations performed included 62 extrapleural pneumonectomies (70%) and 5 pleurectomies/decortications; procedures for exploration only were performed in 21 patients. Seven (7.9%) patients died postoperatively. Adjuvant radiation administered to 57 patients (54 undergoing extrapleural pneumonectomy and 3 undergoing pleurectomy/decortication) at a median dose of 54 Gy was well tolerated (grade 0-2 fatigue, esophagitis), except for one late esophageal fistula. The median survival was 33.8 months for stage I and II tumors but only 10 months for stage III and IV tumors (P =.04). For the patients undergoing extrapleural pneumonectomy, the sites of recurrence were locoregional in 2, locoregional and distant in 5, and distant only in 30. CONCLUSION: Hemithoracic radiation after complete surgical resection at a dose not previously reported is feasible. This approach dramatically reduces local recurrence and is associated with prolonged survival for early-stage tumors. Stage III disease has a high risk of early distant relapse and should be considered for trials of systemic therapy added to this regimen of resection and radiation.

Induction chemotherapy plus three-dimensional conformal radiation therapy in the definitive treatment of locally advanced non-small-cell lung cancer.

PURPOSE: To evaluate our institution's experience using chemotherapy in conjunction with three-dimensional conformal radiation therapy (3D-CRT). METHODS AND MATERIALS: From 1991 to 1998, 152 patients with Stage III non-small-cell lung cancer (NSCLC) were treated with 3D-CRT at Memorial Sloan-Kettering Cancer Center. A total of 137 patients (90%) were surgically staged with either thoracotomy or mediastinoscopy. The remainder were staged radiographically. Seventy patients were treated with radiation therapy alone, and 82 patients received induction chemotherapy before radiation. The majority of chemotherapy-treated patients received a platinum-containing regimen. Radiation was delivered with a 3D conformal technique using CT-based treatment planning. The median dose in the radiation alone group was 70.2 Gy, while in the combined modality group, it was 64.8 Gy. RESULTS: The median follow-up time was 30.5 months among survivors. Stage IIIB disease was present in 36 patients (51%) in the radiation-alone group and 57 patients (70%) in the combined-modality group. Thirty-nine patients had poor prognostic factors (KPS < 70 or weight loss > 5%), and they were equally distributed between the two groups. The median survival times for the radiation-alone and the combined-modality groups were 11.7 months and 18.1 months, respectively (p = 0.001). The 2-year rates of local control in the radiation-alone and combined-modality groups were 35.4% and 43.1%, respectively (p = 0.1). Grade 3 or worse nonhematologic toxicity occurred in 20% of the patients receiving radiation alone and in 16% of those receiving chemotherapy and radiation. Overall, there were only 4 cases of Grade 3 or worse esophagitis. CONCLUSION: Despite more Stage IIIB patients in the combined-modality group, the addition of chemotherapy to 3D-CRT produced a survival advantage over 3D-CRT alone in Stage III NSCLC without a concomitant increase in toxicity. Chemotherapy thus appears to be beneficial, even in patients who are receiving higher doses of radiation therapy than are typically given with conventional techniques. Because locoregional failure remains a major challenge in patients with advanced disease, 3D-CRT in conjunction with chemotherapy may allow safe treatment to the dose levels required to further enhance local control.

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.

Failure of a 3D conformal boost to improve radiotherapy for nasopharyngeal carcinoma.

PURPOSE: To determine whether the use of 3-dimensional (3D) boost for patients with nasopharynx cancer improves local control and reduces the risk of long-term complications. METHODS AND MATERIALS: From 1988 to 1998, 68 patients with nasopharynx cancer received conventional external beam therapy followed by a 3D boost. Disease characteristics of treated patients were as follows: WHO I histology 7%, WHO II 62%, WHO III 31%, clinical AJCC stage T1--2 45%, T3--4 55%, N0--1 63%, N2--3 37%, M0 100%. The median radiation dose was 70 Gy (68--75.6 Gy). Thirty-five patients (52%) received cisplatin-based chemotherapy. The median follow-up of surviving patients was 42 months (12--118 months). RESULTS: Five-year actuarial local control was 77%, regional control was 97%, progression-free survival was 56%, and overall survival was 58%. Stage was the only identifiable prognostic factor: 5-year progression-free survival was 65% for Stages I--III vs. 40% for Stage IV (p = 0.01). The incidence of Grade 3-4 complications was 25% and included hearing loss, trismus, dysphagia, chronic sinusitis, and cranial neuropathy. These results are comparable to outcomes reported with conventional radiation techniques for similarly staged patients. CONCLUSION: The lack of a major benefit with the 3D boost may be related to the fact that CT planning was only used for a fraction of the total dose. We are now using intensity modulated radiation therapy to deliver the entire course of radiation. Intensity modulated radiation therapy achieves better conformal distributions than conventional 3D planning, allowing dose escalation and increased normal tissue sparing.

Treatment planning and delivery of intensity-modulated radiation therapy for primary nasopharynx cancer.

PURPOSE: To implement intensity-modulated radiation therapy (IMRT) for primary nasopharynx cancer and to compare this technique with conventional treatment methods. METHODS AND MATERIALS: Between May 1998 and June 2000, 23 patients with primary nasopharynx cancer were treated with IMRT delivered with dynamic multileaf collimation. Treatments were designed using an inverse planning algorithm, which accepts dose and dose-volume constraints for targets and normal structures. The IMRT plan was compared with a traditional plan consisting of phased lateral fields and a three-dimensional (3D) plan consisting of a combination of lateral fields and a 3D conformal plan. RESULTS: Mean planning target volume (PTV) dose increased from 67.9 Gy with the traditional plan, to 74.6 Gy and 77.3 Gy with the 3D and IMRT plans, respectively. PTV coverage improved in the parapharyngeal region, the skull base, and the medial aspects of the nodal volumes using IMRT and doses to all normal structures decreased compared to the other treatment approaches. Average maximum cord dose decreased from 49 Gy with the traditional plan, to 44 Gy with the 3D plan and 34.5 Gy with IMRT. With the IMRT plan, the volume of mandible and temporal lobes receiving more than 60 Gy decreased by 10-15% compared to the traditional and 3D plans. The mean parotid gland dose decreased with IMRT, although it was not low enough to preserve salivary function. CONCLUSION: Lower normal tissue doses and improved target coverage, primarily in the retropharynx, skull base, and nodal regions, were achieved using IMRT. IMRT could potentially improve locoregional control and toxicity at current dose levels or facilitate dose escalation to further enhance locoregional control.

Accelerated concomitant boost radiotherapy and chemotherapy for advanced nasopharyngeal carcinoma.

PURPOSE: To evaluate the feasibility and efficacy of concomitant boost radiotherapy (RT) plus cisplatin-based chemotherapy compared with standard fractionation RT for patients with advanced nasopharyngeal cancer. PATIENTS AND METHODS: From 1988 through 1999, 50 patients with American Joint Committee on Cancer stage II-IVb nasopharyngeal carcinoma were treated with 70-Gy concomitant boost RT (1.8 Gy/d, weeks 1 through 6; 1.6 Gy second daily fraction, weeks 5 through 6) and two cycles of concurrent cisplatin 100 mg/m(2) days 1 and 22. Thirty-seven patients also received three cycles of cisplatin-based adjuvant chemotherapy. These 50 patients were compared with a nonrandomized cohort of 51 patients with nasopharyngeal cancer treated with 70-Gy standard fractionation RT (1.8 Gy/d) without chemotherapy from 1988 through 1995. The groups were well matched for prognostic factors except stage, for which the concomitant boost RT/chemotherapy group was more advanced (54%, T3-4; 54%, N2-3; 44%, stage IV) compared with the standard RT group (31%, T3-4, P =.03; 22%, N2-3, P <.001; 20%, stage IV, P <.01). RESULTS: With a median follow-up of 42 months (range, 12 to 129 months), the 3-year actuarial local control, progression-free survival, and survival rates were 89% v 74% (P <.01), 66% v 54% (P =.01), and 84% v 71% (P =.04) for the concomitant boost RT/chemotherapy group and the standard RT patients, respectively. Acute grade 3 mucositis was more prevalent with combined therapy, 84% v 43% (P <.001), resulting in a higher rate of temporary gastrostomy tube placement, 46% v 20% (P <.01). CONCLUSION: Concomitant boost RT with cisplatin-based chemotherapy is feasible and improves local-regional control as well as survival for patients with advanced nasopharyngeal cancer compared with standard RT alone.

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.