Postoperative radiotherapy in non-small-cell lung cancer warrants further exploration in the era of adjuvant chemotherapy and conformal radiotherapy.
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Carcinoma, Non-Small-Cell Lung↗
Biomedical subjects
Sharon A Spencer
Publications and source records attributed to Sharon A Spencer.
Women with pathologic stage I, II, and III non-small cell lung cancer have better survival than men.
OBJECTIVE: Bronchogenic malignancy is the number one cause of cancer deaths in both men and women worldwide. National registry-based studies have shown gender disparity in clinicopathologic characteristics and in survival. This study evaluates the risk factors and trends of lung cancer between genders. METHODS: A prospective cohort of consecutive patients with non-small cell lung cancer (NSCLC) who were carefully clinically (all underwent dedicated positron emission tomography scans) and pathologically staged with stage I, II, or III disease underwent homogenous treatment algorithms and were followed up over a period of 7 years. Primary outcomes were 5-year survival and response to neoadjuvant therapy. RESULTS: There were 1,085 patients (671 men and 414 women). Groups were similar for race, pulmonary function, smoking history, comorbidities, neoadjuvant therapy, histology, and resection rates. Women were younger (p = 0.014), had a higher incidence of adenocarcinoma (p = 0.01), and presented at an earlier pathologic stage (p = 0.01) than men. The overall age-adjusted and stage-adjusted 5-year survival rate favored women (60% vs 50%, respectively; p < 0.001). Women had better stage-specific 5-year survival rates (stage I disease, 69% vs 64%, respectively [p = 0.034]; stage II disease, 60% vs 50%, respectively [p = 0.042]; and stage III disease, 46% vs 37%, respectively [p = 0.024]). Women who received neoadjuvant chemotherapy alone (n = 76) were more likely to be a complete or partial responder than men (n = 142; p = 0.025). CONCLUSIONS: Despite uniform staging and treatment, the 5-year survival rate of women with stage I to III NSCLC was better than men overall and at each stage. Women are more likely to have adenocarcinoma, to present with earlier stage disease, and to be younger. Interestingly, women respond better to neoadjuvant chemotherapy.
Adult↗
Phase I/IIa study of cisplatin and gemcitabine as induction chemotherapy followed by concurrent chemoradiotherapy with gemcitabine and paclitaxel for locally advanced non-small-cell lung cancer.
PURPOSE: This is a phase I/IIa study to assess tolerance of gemcitabine and paclitaxel with radiotherapy in locally advanced non-small-cell lung cancer after induction chemotherapy. PATIENTS AND METHODS: Fifty-seven patients with stage III non-small-cell lung cancer were treated with cisplatin 80 mg/m2 on days 1 and 22 and gemcitabine 1,250 mg/m2 on days 1, 8, 22, and 28. Chemoradiotherapy began on day 43 as follows: cohort 1 (n = 9), gemcitabine 300 mg/m2 and paclitaxel 35 mg/m2 weekly (except week 9); cohort 2 (n = 9), gemcitabine 150 mg/m2 and paclitaxel 35 mg/m2 weekly (except week 9); cohort 3 (n = 10) and the 25 phase IIa patients, gemcitabine 300 mg/m2 and paclitaxel 135 mg/m2 every 21 days. Patients were treated with three-dimensional thoracic radiotherapy concurrently to 60 Gy. RESULTS: Weekly chemotherapy resulted in grade 4 esophageal and grade 3 or higher pulmonary toxicities. Reduction in dose density (cohort 3) led to a tolerable toxicity profile and was chosen as the phase IIa regimen. The response rate to induction was 49%, with stable disease in 40% of the patients. The response rate after consolidation therapy was 75% (94% for weekly chemotherapy v 82% for every 3 weeks). Median survival was 23 months, and 3-year survival was 45% for eligible patients. Local relapse occurred in 20% of the patients. Performance status of more than 1 predicted for poor outcome, but baseline pulmonary function did not. Dosimetric parameters including V15, V20, V30 (percent lung volume receiving > or = 15, > or = 20, and > or = 30 Gy, respectively), and mean lung dose correlated with pulmonary toxicity. CONCLUSION: Additional investigation with the 3-week schedule is warranted in patients with a good performance status based on the safety profile and preliminary efficacy data observed in this study.
Adult↗
Pulmonary resection after high-dose and low-dose chest irradiation.
BACKGROUND: The purpose of this study is to assess the safety and efficacy of pulmonary resection after low and high dose neoadjuvant radiotherapy with concurrent chemotherapy. PATIENTS AND METHODS: A retrospective cohort study using an electronic prospective database from January 1998 to August 2004. All patients had N2, stage IIIa, nonsmall cell lung cancer, and received neoadjuvant carboplatinum-based chemotherapy with similar doses. In addition, some patients received high-dose chest radiation (HD) equal to or greater than 60 Gy and were compared with those who received low-dose radiation (LD) less than 60 Gy. All bronchial stumps were buttressed with an intercostal muscle. RESULTS: There were 104 patients, 50 in the LD group and 54 patients in the HD group. Median dose of radiation was 45 Gy (range 35-50.4) in the LD group and 60 Gy (range 60-66.7) in the HD group. Complete pathologic response rate was 10% compared to 28% favoring the HD group (p = 0.04). Median length of stay for both groups was 4 days and the ICU was avoided in 74%. Major morbidity and mortality rates were similar: 8% compared to 9% and 2% compared to 3.7% for the low and high dose groups, respectively. Pneumonectomy was a significant risk factor for morbidity (OR = 17.0). CONCLUSIONS: Pulmonary resection after preoperative chest radiation is safe even after 60 Gy or higher. Sixty or higher may afford an increase in complete pathologic response and it does not seem to increase morbidity or mortality. However, if pneumonectomy is known to be required we prefer to avoid neoadjuvant radiotherapy and use chemotherapy alone.
Adult↗
Simultaneous optimization of sequential IMRT plans.
Radiotherapy often comprises two phases, in which irradiation of a volume at risk for microscopic disease is followed by a sequential dose escalation to a smaller volume either at a higher risk for microscopic disease or containing only gross disease. This technique is difficult to implement with intensity modulated radiotherapy, as the tolerance doses of critical structures must be respected over the sum of the two plans. Techniques that include an integrated boost have been proposed to address this problem. However, clinical experience with such techniques is limited, and many clinicians are uncomfortable prescribing nonconventional fractionation schemes. To solve this problem, we developed an optimization technique that simultaneously generates sequential initial and boost IMRT plans. We have developed an optimization tool that uses a commercial treatment planning system (TPS) and a high level programming language for technical computing. The tool uses the TPS to calculate the dose deposition coefficients (DDCs) for optimization. The DDCs were imported into external software and the treatment ports duplicated to create the boost plan. The initial, boost, and tolerance doses were specified and used to construct cost functions. The initial and boost plans were optimized simultaneously using a gradient search technique. Following optimization, the fluence maps were exported to the TPS for dose calculation. Seven patients treated using sequential techniques were selected from our clinical database. The initial and boost plans used to treat these patients were developed independently of each other by dividing the tolerance doses proportionally between the initial and boost plans and then iteratively optimizing the plans until a summation that met the treatment goals was obtained. We used the simultaneous optimization technique to generate plans that met the original planning goals. The coverage of the initial and boost target volumes in the simultaneously optimized plans was equivalent to the independently optimized plans actually used for treatment. Tolerance doses of the critical structures were respected for the plan sum; however, the dose to critical structures for the individual initial and boost plans was different between the simultaneously optimized and the independently optimized plans. In conclusion, we have demonstrated a method for optimization of initial and boost plans that treat volume reductions using the same dose per fraction. The method is efficient, as it avoids the iterative approach necessitated by currently available TPSs, and is generalizable to more than two treatment phases. Comparison with clinical plans developed independently suggests that current manual techniques for planning sequential treatments may be suboptimal.
Algorithms↗
A dynamic supraclavicular field-matching technique for head-and-neck cancer patients treated with IMRT.
PURPOSE: The conventional single-isocenter and half-beam (SIHB) technique for matching supraclavicular fields with head-and-neck (HN) intensity-modulated radiotherapy (IMRT) fields is subject to substantial dose inhomogeneities from imperfect accelerator jaw/MLC calibration. It also limits the isocenter location and restricts the useful field size for IMRT. We propose a dynamic field-matching technique to overcome these limitations. METHODS AND MATERIALS: The proposed dynamic field-matching technique makes use of wedge junctions for the abutment of supraclavicular and HN IMRT fields. The supraclavicular field was shaped with a multileaf collimator (MLC), which was orientated such that the leaves traveled along the superoinferior direction. The leaves that defined the superior field border moved continuously during treatment from 1.5 cm below to 1.5 cm above the conventional match line to generate a 3-cm-wide wedge-shaped junction. The HN IMRT fields were optimized by taking into account the dose contribution from the supraclavicular field to the junction area, which generates a complementary wedge to produce a smooth junction in the abutment region. This technique was evaluated on a polystyrene phantom and 10 HN cancer patients. Treatment plans were generated for the phantom and the 10 patients. Dose profiles across the abutment region were measured in the phantom on films. For patient plans, dose profiles that passed through the center of the neck lymph nodes were calculated using the proposed technique and the SIHB technique, and dose uniformity in the abutment region was compared. Field mismatches of +/- 1 mm and +/- 2 mm because of imperfect jaw/MLC calibration were simulated, and the resulting dose inhomogeneities were studied for the two techniques with film measurements and patient plans. Three-dimensional volumetric doses were analyzed, and equivalent uniform doses (EUD) were computed. The effect of field mismatches on EUD was compared for the two match techniques. RESULTS: For a perfect jaw/MLC calibration, dose profiles for the 10 patients in the 3-cm match zone had an average inhomogeneity range of -1.6% to +1.6% using the dynamic-matching technique and -3.7% to +3.8% according to the SIHB technique. Measurements showed that dose inhomogeneities that resulted from 1-mm and 2-mm jaw/MLC calibration errors were reduced from as large as 27% and 45% with the SIHB technique to less than 2% and 5.7% with the dynamic technique, respectively. For -1-mm, -2-mm, +1-mm, and +2-mm jaw/MLC calibration errors, respectively, treatment plans for the 10 patients yielded average dose inhomogeneities of -5.9%, -3.0%, +2.7%, and +5.8% with the dynamic technique as compared to -22.8%, -11.1%, +9.8%, and +22.1% with the SIHB technique. Calculation based on a dose-volume histogram (DVH) showed that the SIHB technique resulted in larger changes in EUD of the PTV in the junction area than did the dynamic technique. CONCLUSION: Compared with the conventional SIHB technique, the dynamic field-matching technique provides superior dose homogeneity in the abutment region between the supraclavicular and HN IMRT fields. The dynamic feathering mechanism substantially reduces dose inhomogeneities that result from imperfect jaw/MLC calibration. In addition, isocenter location in the dynamic field-matching technique can be chosen for reproducible patient setup and for adequate IMRT field size rather than being dictated by the match position. It also allows angling of the supraclavicular field to reduce the volume of healthy lung irradiated, which is impractical with the SIHB technique. In principle, this technique should be applicable to any treatment site that requires the abutment of static and intensity-modulated fields.
Calibration↗
Validation of target volume and position in respiratory gated CT planning and treatment.
The capability of a commercial respiratory gating system based on video tracking of reflective markers to reduce motion-induced CT planning and treatment errors was evaluated. Spherical plastic shells (2.8-82 cm3), simulating the gross target volume (GTV), were placed in a water-filled body phantom that was moved sinusoidally along the longitudinal axis of the CT scanner and the accelerator for +/- 1 cm at 15-30 cycle/min. During gated CT imaging, the x-ray exposure was initiated by the gating system shortly before the end of expiration (so that the imaging time would be centered at the end of expiration); it was terminated by the scanner after completion of each slice. In nongated CT images, the target appeared distorted and often broken up. GTVs volume errors ranged 16%-110% in axial scans, and 7%-36% in spiral scans. In gated CT images, the spheres appeared 3 and 5 mm longer than their actual diameters (volume errors 2%-16%), at the respective respiration rates of 15 and 20 cycles/min. At 30 cycles/min the target appeared 1 cm longer, and volume error ranged 25%-53%. During treatment, gating kept the beam on for a duration equal to the CT acquisition time of 1 s/slice. The difference in positional errors between gated CT and portal films was 1 mm, regardless the size of residual motion errors. Because of the potential of suboptimal placement of the gating window between CT imaging and treatment, an extra 1.5-2.5 mm safety margin can be added regardless of the size of residual motion error. For respiratory rates > or = 30 cycles/min, the effectiveness of gating is limited by large residual motion in the 1 s CT acquisition time.
Humans↗
Concurrent chemoradiation therapy with cisplatin and paclitaxel for locally advanced non-small cell lung cancer: long-term follow-up of a phase I trial.
The purpose of this trial was to evaluate the feasibility of concurrent paclitaxel/cisplatin and conventional thoracic irradiation in locally advanced non-small cell lung cancer (NSCLC). Ambulatory patients with medically inoperable or unresectable stage II-III NSCLC, and performance status 0-2 were eligible. Patients were not excluded from this trial if they had lost more than 5% of their body weight during the preceding 3 months, and/or if they had small ipsilateral pleural effusion. The initial dose of paclitaxel/cisplatin was 110 and 50 mg/m(2), and was escalated through five dose levels. Four cycles of chemotherapy were planned; the first two cycles were given concurrently with radiotherapy (4 weeks apart), followed by two additional cycles (every 3 weeks). Conventional chest radiotherapy to a total dose of 60 Gy (2 Gy per day) was delivered in 6 weeks. Forty-three patients were enrolled of which 38 were evaluable for response. Dose-limiting toxicities were grade 4 neutropenia (43% of patients) and grade 3 esophagitis (26% of patients) during the chemoradiotherapy phase. Grade > or = 2 acute and late pulmonary toxicity occurred in 10 and 68% of the patients, respectively. In most patients, prompt symptomatic and radiologic improvement was observed with early steroid administration. The volume of lung receiving 15-30 Gy was correlated with late pulmonary toxicity. The overall response was 84% with ten complete and 22 partial responses. The median survival was 16.5 months (95% confidence interval, 9.5 to 25) for those patients evaluable for response. After a median follow-up of 70 months, 5 (13%) patients are alive without evidence of disease. The maximum tolerated dose (MTD) of paclitaxel and cisplatin with concurrent radiotherapy is at dose level 3 paclitaxel (135 mg/m(2)) and cisplatin (75 mg/m(2)). Toxicity, although significant, was manageable in the great majority of the patients. The activity observed with this regimen is particularly noteworthy when considering the advanced nature of these patients, and the fact that patients (N=18) with poor risk factors were included in the study.
Adolescent↗
Role of radiation therapy and radiosurgery in glioblastoma multiforme.
Randomized trials have supported a role for radiation therapy in the initial management of Glioblastoma Multiforme (GBM) for over twenty-five years. Although technological advances in imaging and three-dimensional treatment planning have reduced the toxicity for patients and have allowed safe radiation dose escalation, unfortunately they have not produced a correspondingly dramatic improvement in overall survival. The dose of 60 Gy partial brain RT remains the standard of care for patients with newly diagnosed GBM. Recently completed randomized trials of brachytherapy and radiosurgery do not support these modalities in the initial management of GBM, but these and other focal RT techniques such as intensity modulated radiation therapy enable safe retreatment in selected patients. Future studies will need to explore radiation biologic response modification and radiosensitization through targeted therapies.
Brachytherapy↗