Kimberly M. Creach

Combined PET/CT image characteristics for radiotherapy tumor response in lung cancer

BACKGROUND AND PURPOSE Prediction of local failure in radiotherapy patients with non-small cell lung cancer (NSCLC) remains a challenging task. Recent evidence suggests that FDG-PET images can be used to predict outcomes. We investigate an alternative multimodality image-feature approach for predicting post-radiotherapy tumor progression in NSCLC. MATERIAL AND METHODS We analyzed pre-treatment FDG-PET/CT studies of twenty-seven NSCLC patients for local and loco-regional failures. Thirty-two tumor region features based on SUV or HU, intensity-volume-histogram (IVH) and texture characteristics were extracted. Statistical analysis was performed using Spearmans correlation (rs) and multivariable logistic regression. RESULTS For loco-regional recurrence, IVH variables had the highest univariate association. In PET, IVH-slope reached rs=0.3426 (p=0.0403). Motion correction slightly improved correlation of texture features. In CT, coefficient of variation had the highest association rs=-0.2665 (p=0.0871). Similarly for local failure, a CT-IVH parameter reached rs=0.4530 (p=0.0105). For loco-regional and local failures, a 2-parameter model of PET-V(80) and CT-V(70) yielded rs=0.4854 (p=0.0067) and rs=0.5908 (p=0.0013), respectively. Addition of dosimetric variables provided improvement in cases of loco-regional but not local failures. CONCLUSIONS We proposed a feature-based approach to evaluate radiation tumor response. Our study demonstrates that multimodality image-feature modeling provides better performance compared to existing metrics and holds promise for individualizing radiotherapy planning.

Dose-response for stereotactic body radiotherapy in early-stage non-small-cell lung cancer

PURPOSE To compare the efficacy of three lung stereotactic body radiotherapy (SBRT) regimens in a large institutional cohort. METHODS Between 2004 and 2009, 130 patients underwent definitive lung cancer SBRT to a single lesion at the Mallinckrodt Institute of Radiology. We delivered 18 Gy × 3 fractions for peripheral tumors (n = 111) and either 9 Gy × 5 fractions (n = 8) or 10 Gy × 5 fractions (n = 11) for tumors that were central or near critical structures. Univariate and multivariate analysis of prognostic factors was performed using the Cox proportional hazard model. RESULTS Median follow-up was 11, 16, and 13 months for the 9 Gy × 5, 10 Gy × 5, and 18 Gy × 3 groups, respectively. Local control statistics for Years 1 and 2 were, respectively, 75% and 50% for 9 Gy × 5, 100% and 100% for 10 Gy × 5, and 99% and 91% for 18 Gy × 3. Median overall survival was 14 months, not reached, and 34 months for the 9 Gy × 5, 10 Gy × 5, and 18 Gy × 3 treatments, respectively. No difference in local control or overall survival was found between the 10 Gy × 5 and 18 Gy × 3 groups on log-rank test, but both groups had improved local control and overall survival compared with 9 Gy × 5. Treatment with 9 Gy × 5 was the only independent prognostic factor for reduced local control on multivariate analysis, and increasing age, increasing tumor volume, and poor performance status predicted independently for reduced overall survival. CONCLUSION Treatment regimens of 10 Gy × 5 and 18 Gy × 3 seem to be efficacious for lung cancer SBRT and provide superior local control and overall survival compared with 9 Gy × 5.

Patterns of failure after stereotactic body radiation therapy or lobar resection for clinical stage I non-small-cell lung cancer.

Introduction: The purpose of this study was to compare patterns of failure between lobar resection (lobectomy or pneumonectomy) and stereotactic body radiation therapy (SBRT) for patients with clinical stage I non–small-cell lung cancer (NSCLC). Methods: From January 2004 to January 2008, 338 patients underwent definitive treatment for pathologically confirmed clinical stage I NSCLC with lobar resection (n = 260) or SBRT (n = 78). Most surgical patients underwent lobectomy (n = 237). SBRT patients received a biologically effective dose of at least 100 Gy10. Lobar resection patients were younger, healthier, and had superior pulmonary function, whereas most of the patients in the SBRT group had T1 tumors. Final pathology upstaged 32.7% of surgery patients, and 20.0% received adjuvant chemotherapy. No SBRT patients received adjuvant chemotherapy. Results: In an unmatched comparison, 4-year lobar local control (98.7% versus 93.6%, p = 0.015) was greater for lobar resection versus SBRT, respectively, though primary tumor (98.7% versus 95.3%, p = 0.088), regional (82.9% versus 78.1%, p = 0.912), and distant control (76.1% versus 54.0%, p = 0.152) were similar. Overall survival (OS, 63.5% versus 29.6%, p < 0.0001) was greater for lobar resection, though cause-specific survival (CSS, 81.3% versus 75.3%, p = 0.923) was similar. In a T-stage matched comparison of 152 patients, there was no significant difference in patterns of failure or CSS, whereas OS favored surgery. Conclusion: Lobectomy/pneumonectomy or SBRT results in comparable patterns of failure for clinical stage I NSCLC. In this retrospective comparison, OS was superior for surgery, though CSS was similar. Randomized trials are necessary to control for fundamental differences in comorbidity, which impact interpretation of both tumor control and survival.

Dosimetric predictors of chest wall pain after lung stereotactic body radiotherapy

PURPOSE To identify risk factors for the development of chest wall (CW) pain after thoracic stereotactic body radiotherapy (SBRT). METHODS AND MATERIALS A registry of patients with lung lesions treated with lung SBRT was explored to identify patients treated with 54 Gy in three fractions or 50 Gy in five fractions. One hundred and forty-six lesions in 140 patients were identified; complete electronic treatment plans were available on 86 CWs. The CW was contoured as a 3 cm outward expansion from the involved lung. Univariate and multivariate analyses were used to correlate patient, tumor, and dosimetric factors to the development of CW toxicity. RESULTS CW pain occurred in 22 patients (15.7%). The Kaplan-Meier estimated risk of CW pain at 2 years was 20.1% (95% C.I., 13.2-28.8%). On univariate analysis of patient factors, elevated BMI (p=0.026) and connective tissue disease (p=0.036) correlated with CW pain. The percent of CW receiving 30, 35, or 40 Gy was most predictive of CW pain on multivariate analysis using logistic regression, while V40 alone was predictive using Cox regression. A V30 threshold of 0.7% and V40 threshold of 0.19% was correlated with a 15% risk of CW pain. CONCLUSIONS We have described patient and dosimetric parameters that correlate with CW pain after lung SBRT. The risk of CW pain may be mitigated by attempting to reduce the relative proportion of CW receiving 30-40 Gy during treatment planning.

Fiducial placement for stereotactic radiation by using EUS: feasibility when using a marker compatible with a standard 22-gauge needle

BACKGROUND Stereotactic radiation by using fiducial markers permits higher doses of radiation while reducing the exposure of uninvolved, adjacent structures. EUS has been used to deploy fiducials, although a 19-gauge needle has traditionally been required. OBJECTIVE To report a new technique and the feasibility of deploying a fiducial compatible with a 22-gauge needle under EUS guidance. DESIGN Single-center, case series. SETTING Tertiary care referral center. PATIENTS Thirteen patients with primary or metastatic cancer referred for stereotactic radiation. INTERVENTIONS EUS-guided placement of a single fiducial marker that is compatible with a 22-gauge EUS-FNA needle. MAIN OUTCOME MEASUREMENTS Technical success and complications. RESULTS Thirteen patients referred for EUS-guided placement of a fiducial marker were identified in the endoscopic database. Targeted lesions measured 27 +/- 13 mm (range 8-50) x 21 +/- 10 mm (range 6-42). All fiducials were successfully deployed, 9 using a transgastric and 4 using a transduodenal approach. There were no EUS-associated complications. Two patients did not proceed to radiation therapy as a result of interval peritoneal metastasis. However, all fiducials were visible on the roentogram. Eleven of 13 patients (85%) required placement of 1 fiducial, whereas 2 patients (15%) required 2 fiducials. LIMITATIONS Uncontrolled feasibility study with limited sample size and follow-up. CONCLUSION EUS-guided placement of a fiducial using a 22-gauge needle is technically feasible and may permit greater access compared with the 19-gauge needle technique.

Radioactive iodine therapy decreases recurrence in thyroid papillary microcarcinoma.

Background. The most appropriate therapy for papillary microcarcinoma (PMC) is controversial. Methods. We reviewed the therapy and outcome of 407 patients with PMC. Results. Three hundred-eighty patients underwent total thyroidectomy, and 349 patients received I-131 therapy. The median followup was 5.3 years. Forty patients developed recurrent disease. On univariate analysis, development of disease recurrence was correlated with histological tumor size > 0.8 cm (P = 0.0104), age < 45 years (P = 0.043), and no I-131 therapy (P < 0.0001). On multivariate analysis, histological tumor size > 0.8 cm, positive lymph nodes, and no I-131 therapy were significant. The 5-year RFS for patients treated with I-131 was 95.0% versus 78.6% (P < 0.0001) for patients not treated with I-131. Patients with lymph node metastasis who did not receive I-131 had a 5-year RFS of 42.9% versus 93.2% (P < 0.0001) for patients who received I-131. Conclusions. Recommend I-131 remnant ablation for patients with PMC, particularly patients with lymph node metastasis.

Stereotactic body radiation therapy in the treatment of multiple primary lung cancers

BACKGROUND AND PURPOSE Patients with multiple primary lung cancers (MPLC) present a therapeutic dilemma, particularly when they are at high risk for surgical resection. We evaluated the role of stereotactic body radiation therapy (SBRT) in the treatment of MPLC. MATERIALS AND METHODS A prospective thoracic SBRT registry was explored for patients with either synchronous or metachronous MPLC treated with SBRT for one or both of their tumors. Sixty-three patients were identified and clinical data were analyzed. RESULTS Fifteen patients had synchronous lesions and 48 patients had metachronous lesions. Seventy-six lesions were treated with SBRT. Median follow-up was 24 months for living patients. Median progression-free survival (PFS) and overall survival (OS) for the entire cohort was 15.5 and 20 months, respectively. Patients with metachronous MPLC had a significantly higher 2 year PFS (53.3% vs. 0%, p=0.0466) compared to patients with synchronous MPLC. Likewise, 2 year OS was also superior for patients with metachronous versus synchronous MPLC (68.1% vs. 27.5%, p=0.0014). Six tumors (7.9%) recurred within the radiation field. There were no grade ≥3 toxicities. CONCLUSIONS SBRT for patients with MPLC appears to be a safe and effective local treatment alternative to surgery, particularly for medically inoperable patients. Patients with metachronous MPLC have encouraging survival rates, and thus local therapy appears justified. However, patients with synchronous MPLC have poor OS and PFS despite having excellent local control, and thus the utility of local therapy in this population requires further study.

Stereotactic body radiation therapy for the treatment of early-stage minimally invasive adenocarcinoma or adenocarcnioma in situ (formerly bronchioloalveolar carcinoma): a patterns of failure analysis

IntroductionOngoing prospective trials exploring stereotactic body radiation therapy (SBRT) for early stage non-small cell lung cancer (NSCLC) often exclude minimally invasive adenocarcinoma or adenocarcnioma in situ, formerly bronchioloalveolar carcinoma (BAC), due to concerns for accurate target delineation on CT. We performed a patterns of failure analysis to compare outcomes between BAC and other NSCLC subtypes.MethodsOne hundred twenty patients with early stage NSCLC were treated with SBRT from 2004–2009. Pathologic confirmation of NSCLC was obtained in 97 patients. Radiotherapy was delivered according to RTOG guidelines. The log-rank test was used to compare outcomes between BAC and other NSCLC.ResultsMedian follow-up was 29 months. The median SBRT dose was 5400 cGy. Thirteen patients had radiographically diagnosed BAC and five patients had biopsy confirmed BAC, of which two had both. The three-year local control was 100% for biopsy-proven or radiographically diagnosed BAC (n = 18) and 86% for all other NSCLC subtypes (n = 102) (p = 0.13). Likewise, no significant difference was detected between BAC and other NSCLC for 3-year regional failure (12% vs. 20%, p = 0.45), progression-free survival (57.6% vs. 53.5%, p = 0.84) or overall survival (35% vs. 47%, p = 0.66). There was a trend towards lower three-year rates of freedom from distant failure in patients with any diagnosis of BAC compared to those without (26% vs. 38%, p = 0.053).ConclusionsCompared to other NSCLC subtypes, BAC appears to have similar patterns of failure and survival after treatment with SBRT, however there may be an increased risk of distant metastases with BAC. RTOG guideline-based target delineation provides encouraging local control rates for patients with BAC.

Thyroid carcinoma uptake of 18 F-Fluorodeoxyglucose in patients with elevated serum thyroglobulin and negative 131I scintigraphy

PURPOSE To determine if FDG-PET results can predict for outcome in thyroid cancer patients with elevated Tg and negative I-131 imaging. MATERIALS AND METHODS We conducted a retrospective review of 76 patients who had elevated serum Tg and negative (131)I scintigraphy and who underwent FDG-PET. After FDG-PET, patients underwent neck dissection or radiation. RESULTS The 51 patients with positive FDG-PET had a 5-year survival of 63% compared to 100% (p<0.049) for the 25 patients with negative PET. Patients with FDG-avid disease isolated to the lymph nodes had 5-year CSS of 91% compared to 32% (p=0.0033) for those with disease outside the regional lymph nodes. Twenty-nine patients with disease isolated to the regional lymph nodes underwent salvage neck dissection and 22 remain NED after 28 months. CONCLUSIONS Negative FDG-PET with elevated Tg predicts an excellent outcome. FDG-avid disease isolated to the regional lymph nodes had a low likelihood of death due to thyroid cancer.

Management of cervical nodal metastasis detected on I-131 scintigraphy after initial surgery of well-differentiated thyroid carcinoma

BACKGROUND The purpose of this study was to evaluate the outcome of patients with differentiated thyroid carcinoma whose posttherapy imaging demonstrated I-131 uptake in cervical lymph nodes. METHODS In this prospective cohort study, 95 patients who underwent surgery for well-differentiated thyroid carcinoma had evidence of persistent cervical lymph node metastasis on posttherapy I-131 scintigraphy. These patients were evaluated by subsequent I-131 scintigraphy, and treated with additional I-131 therapy or surgical excision of cervical lymph nodes as clinically indicated. Patients were followed for a mean of 6.8 years. RESULTS Patients received a total of one to three I-131 administrations (median dosage, 235 mCi). Surveillance I-131 scintigraphy was performed to evaluate disease activity. I-131 uptake was eliminated from the thyroid bed in all patients. Persistent disease was detected in cervical lymph nodes in 9 (9%) of 95 patients, and these 9 patients underwent lymph node excision (1 patient later had recurrent disease and was treated with additional I-131 therapy). All patients subsequently had negative I-131 imaging and undetectable serum thyroglobulin. Of the 95 patients in the study, 9 (9%) developed recurrent disease in cervical lymph nodes. Of these 9 patients, 2 also had distant metastases; 6 of these patients underwent surgical excision of cervical adenopathy, and 3 received additional I-131 therapy. There were no grade >3 toxicities attributable to I-131. At last follow-up, 93 (98%) of the 95 patients were free of disease. CONCLUSION Most patients (82%) in the study with cervical lymph node metastases detected on initial posttherapy I-131 scintigraphy were rendered free of disease with I-131 therapy. Surgical reintervention was required in 15% of patients (15/95). The use and timing of additional I-131 therapy versus surgical intervention in this group of patients needs to be further evaluated.