Preoperative short-course radiation therapy for rectal cancer provides excellent disease control and toxicity: Results from a single US institution.

PURPOSE: Preoperative short-course radiation therapy (SCRT) has rarely been used for rectal cancer in the United States, although 2 randomized phase 3 trials demonstrate equivalence to conventional chemoradiation (CRT), and recent updates to national guidelines include this regimen as a treatment option. We sought to evaluate the efficacy and safety of preoperative SCRT followed by immediate surgery within 1 week to treat rectal cancer in the US setting. METHODS AND MATERIALS: All patients treated with preoperative SCRT (4 Gy × 5 fractions for total 20 Gy) followed by planned surgery within 1 week at our institution were retrospectively evaluated. Censored cases with ≥2 years of follow-up were included along with any disease failure or death. Patients with cM1 disease were excluded. Patients with yp stage II/III disease typically received adjuvant chemotherapy from the 1990s onwards. The primary outcomes were actuarial (Kaplan-Meier) 5-year locoregional control (LC), disease-free survival (DFS), and overall survival (OS) as well as late severe (greater than or equal to grade 3) toxicity. RESULTS: Our analysis included 202 consecutive patients with clinical stage I-III disease treated from 1977 through 2011. Median follow-up was 6.5 years (range, 2-29.2). Five-year disease outcomes were 95.9% ± 1.5% for LC, 76.4% ± 3.1% for DFS, and 84.6% ± 2.6% for OS. For patients with locally advanced rectal cancer (cT3-4 and/or cN+), 5-year LC, DFS, and OS were 95.1% ± 2.1%, 73.3% ± 4.3%, and 80.6% ± 3.7%, respectively. The late severe toxicity rate was 11.4%. CONCLUSIONS: SCRT followed by immediate surgery is a safe and effective treatment for patients with rectal cancer in the United States. Though SCRT has not been widely adopted, recent updates to the national guidelines for rectal cancer as well as financial pressures to reduce healthcare costs may lead to increased utilization of this treatment regimen in the future.

Metabolic Tumor Volume on PET Reduced More than Gross Tumor Volume on CT during Radiotherapy in Patients with Non-Small Cell Lung Cancer Treated with 3DCRT or SBRT.

OBJECTIVE: We have previously demonstrated that tumor reduces in activity and size during the course of radiotherapy (RT) in a limited number of patients with non-small cell lung cancer (NSCLC). This study aimed to quantify the metabolic tumor volume (MTV) on PET and compare its changes with those of gross tumor volume (GTV) on CT during-RT for 3D conformal radiotherapy (3DCRT) and stereotactic body radiotherapy (SBRT). METHODS: Patients with stage I-III NSCLC treated with a definitive course of RT ± chemotherapy were eligible for this prospective study. FDG-PET/CT scans were acquired within 2 weeks before RT (pre-RT) and at about two thirds of total dose during-RT. PET-MTVs were delineated using a method combining the tumor/aorta ratio autosegmentation and CT anatomy based manual editing. Data is presented as mean (95% confident interval). RESULTS: The MTV delineation methodology was first confirmed to be highly reproducible by comparing volumes defined by different physicians and using different systems (coefficiency >0.98). Fifty patients with 88 primary and nodal lesions were evaluated. The mean ratios of MTV/GTV were 0.70(-0.07~1.47) and 0.33(-0.30~0.95) for pre-RT and during-RT, respectively. PET-MTV reduced by 70% (62-77%), while CT-GTV by 41% (33-49%) (p< 0.001) during-RT. MTV reduction was 72.9% and 15.4% for 3DCRT and SBRT, respectively (p< 0.001). CONCLUSION: PET-MTV reduced more than CT-GTV during-RT, while patients treated with 3DCRT reduced more than SBRT. RTOG1106 is using during-RT PET-MTV to adapt radiation therapy in 3DCRT.

Natural growth and disease progression of non-small cell lung cancer evaluated with 18F-fluorodeoxyglucose PET/CT.

PURPOSE: The aims of this study were to: (1) estimate the volumetric and metabolic growth rate of non-small cell lung cancer (NSCLC), (2) evaluate disease progression prior to treatment, and (3) explore the effects of tumor growth rate and time to treatment (TTT) on survival outcome. METHODS: Patients with inoperable stages I-III NSCLC with serial pre-treatment PET/CT scans were eligible for this study. PET-derived metabolic tumor volumes (PET-MTV) and CT-derived gross tumor volumes (CT-GTV) were contoured using PET/CT information. Normalized standardized uptake values (NSUV) in tumors including the NSUVmean and NSUVmax were measured. Tumor growth rates expressed as doubling time (DT) were estimated using an exponential model. Pre-treatment disease progression defined as the development of any new site of disease on PET/CT and change in TNM stage (AJCC 7th ed.) were recorded. Growth rate and tumor progression were analyzed with respect to overall (OS) and progression free survival (PFS). RESULTS: Thirty-four patients with a median inter-scan interval (ISI) of 43 days and TTT of 48 days were analyzed. Tumor volumes showed remarkable inter-scan growth while NSUV did not increase significantly. The DT for PET-MTV, CT-GTV, NSUVmean and NSUVmax were 124, 139, 597, and 333 days, respectively. Pre-treatment disease progression occurred in 20.6% patients with longer ISI being a significant risk factor (OR=1.027, p=0.02). The optimal threshold ISI to predict progression was 58 days (4.8% vs. 46.2%, p=0.007). Neither tumor growth rates nor TTT were significantly correlated to OS or PFS. CONCLUSIONS: NSCLC displays rapid tumor volume growth whereas NSUVmean and NSUVmax are relatively stable over the same time period. Longer delays before initiation of treatment are associated with higher risk of pre-treatment disease progression.

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.

l-[METHYL-(11)C] methionine positron emission tomography for target delineation in malignant gliomas: impact on results of carbon ion radiotherapy.

PURPOSE: To assess the importance of (11)C-methionine (MET)-positron emission tomography (PET) for clinical target volume (CTV) delineation. METHODS AND MATERIALS: This retrospective study analyzed 16 patients with malignant glioma (4 patients, anaplastic astrocytoma; 12 patients, glioblastoma multiforme) treated with surgery and carbon ion radiotherapy from April 2002 to Nov 2005. The MET-PET target volume was compared with gross tumor volume and CTV, defined by using computed tomography/magnetic resonance imaging (MRI). Correlations with treatment results were evaluated between positive and negative extended volumes (EVs) of the MET-PET target for CTV. RESULTS: Mean volumes of the MET-PET targets, CTV1 (defined by means of high-intensity volume on T2-weighted MRI), and CTV2 (defined by means of contrast-enhancement volume on T1-weighted MRI) were 6.35, 264.7, and 117.7 cm(3), respectively. Mean EVs of MET-PET targets for CTV1 and CTV2 were 0.6 and 2.2 cm(3), respectively. The MET-PET target volumes were included in CTV1 and CTV2 in 13 (81.3%) and 11 patients (68.8%), respectively. Patients with a negative EV for CTV1 had significantly greater survival rate (p = 0.0069), regional control (p = 0.0047), and distant control time (p = 0.0267) than those with a positive EV. Distant control time also was better in patients with a negative EV for CTV2 than those with a positive EV (p = 0.0401). CONCLUSIONS: For patients with malignant gliomas, MET-PET has a possibility to be a predictor of outcome in carbon ion radiotherapy. Direct use of MET-PET fused to planning computed tomography will be useful and yield favorable results for the therapy.