Treatment Efficacy Of Preoperative Chemoradiotherapy For Patients With Locally Advanced Non-small cell Lung Cancer

Treatment Efficacy Of Preoperative Chemoradiotherapy For Patients With Locally Advanced Non-small cell Lung Cancer

I. J. Radiation Oncology d Biology d Physics S624 Volume 81, Number 2, Supplement, 2011 included as part of highly selective nodal irradiation; for...

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I. J. Radiation Oncology d Biology d Physics


Volume 81, Number 2, Supplement, 2011

included as part of highly selective nodal irradiation; for left lung tumors, stations 5 and 6 are also needed to be covered. PET/CT should be incorporated into radiotherapy treatment planning for locally advanced NSCLC. Author Disclosure: K. Wu: None. J. Mao: None. H. Qian: None. S. Ren: None. Y. Guan: None.


An Improved Method for Delineating Individualized ITV for SBRT of Lung Cancer


H. Ge , J. Cai2, C. Kelsey2, F. Yin2 1

Henan Cancer Hospital, Zhengzhou, China, 2Duke University Medical Center, Durham, NC

Purpose/Objective(s): Tumor internal target volume (ITV) generated using maximum intensity projection (MIP) of 4D-CT, ITVMIP, tends to underestimate ITV due to irregular breathing. This study aims to investigate the efficacy of a novel method of generating tumor ITV by combining the MIP-based ITV (ITVMIP) and GTV contoured from free-breathing 3D-CT (GTV3D) to improve the accuracy in individualizing ITV determination for lung cancer SBRT. Materials/Methods: This retrospective study included 19 patients of early stage non-small cell lung cancer and 3 patients of pulmonary oligometastases who underwent SBRT. All patients were imaged with both free-breathing 3D-CT and 4D-CT with a real-time position management system for patient breathing signal. For each patient, a MIP was generated from 4D-CT and was exported, along with the 3D-CT, to a treatment planning system for contouring ITVMIP and GTV3D. The ITVCOMB was then generated by combing the two. All volumes for GTV3D, ITVMIP, and ITVCOMB were delineated and measured in the same lung window. An effective tumor diameter (ETD) was estimated for each patient from GTV3D. Tumor motions in superior-inferior (SI), mediolateral (ML), and anterior-posterior (AP) directions, RSI, RML, and RAP, were determined from 4D-CT. Percentage differences between ITVCOMB and GTV3D (E1), and between ITVCOMB and ITVMIP (E2), were determined and correlated to tumor motions and ETD. Results: The ranges (and the means) of tumor motion were 2 - 18mm (7.5mm), 0 - 7.5mm (4.2mm), 2 - 10mm (4.2mm) in SI, ML, AP directions, respectively. The means and standard deviations for GTV3D, ITVMIP, and ITVCOMB were 11.41 ± 9.30 cm3, 13.94 ± 10.94 cm3, and 15.64 ± 11.45 cm3, respectively. E1 was positively correlated with RSI and RML (r = 0.556 and 0.489; p = 0.007 and 0.021) and negatively correlated with ETD(r = -0.530, p = 0.011). No correlation was found between E2 and tumor motion and ETD. Conclusions: ITVMIP from 4D-CT may be insufficient in determining patient-special target volumes. ITVCOMB is clinically feasible and can be used to minimize the ITV underestimation based on ITVMIP. Author Disclosure: H. Ge: None. J. Cai: None. C. Kelsey: None. F. Yin: None.


Stereotactic Body Radiotherapy for Stage I Non-small Cell Lung Cancer Causes Immune Suppression

Y. Maehata, H. Onishi, K. Kuriyama, S. Aoki, M. Araya, R. Saito, M. Oguri, K. Marino, T. Komiyama, T. Araki University of Yamanashi, Yamanashi, Japan Purpose/Objective(s): Stereotactic body radiotherapy (SBRT) is regarded as a radical treatment modality for Stage I non-small cell lung cancer (NSCLC) that may be comparable to surgery. It was reported that surgical stress causes significant immune suppression and progress tumor regrowth or metastases, whereas SBRT is considered to be less invasive. We evaluated immunological response after SBRT for Stage I non-small cell lung cancer. Materials/Methods: Eighteen patients (6 males and 12 females) with a median age of 72 year were examined. The patients underwent SBRT for Stage I non-small-cell lung cancer receiving 40 - 70Gy in 4 - 10 fractions between April 2010 and March 2011, and peripheral blood samples were collected at 3 points; before SBRT, at the last day of SBRT, and a week after completion of SBRT. They were analyzed for the amounts (counts/ml) of total lymphocytes (TL), cluster of differentiation (CD) 4, CD8, CD19, CD56, and natural killer (NK) cells populations. Results: All results of each of cells population were as follows; before SBRT, at the last day, a week after completion, respectively. TL; (1344 ± 533, 995 ± 423, 866 ± 455), CD4; (654 ± 326, 507 ± 271, 460 ± 262), CD8; (291 ± 250, 223 ± 143, 194 ± 191), CD19; (145 ± 76, 72 ± 45, 49 ± 26), CD56; (232 ± 146, 176 ± 103, 170 ± 153), NK; (497 ± 278, 355 ± 211, 279 ± 241). TL and every lymphocyte subset counts reduced significantly after SBRT. Conclusions: SBRT causes immune suppression lasting at least one week. Author Disclosure: Y. Maehata: None. H. Onishi: None. K. Kuriyama: None. S. Aoki: None. M. Araya: None. R. Saito: None. M. Oguri: None. K. Marino: None. T. Komiyama: None. T. Araki: None.


Treatment Efficacy Of Preoperative Chemoradiotherapy For Patients With Locally Advanced Non-small cell Lung Cancer

T. Sasaki1, S. Uehara1, M. Abe1, Y. Shioyama2, K. Nakamura2, K. Sugio1, Y. Ichinose1, H. Hirata2, H. Honda2 1

National Kyushu Cancer Center, Fukuoka 811-1395, Japan, 2Graduate School of Medical Sciences, Kyushu University, Fukuoka 812 - 8582, Japan Purpose/Objective(s): To investigate the therapeutic effectiveness of preoperative chemoradiotherapy with TS-1 which is composed of tegafur (5-FU prodrug), 5-chloro-2, 4-dihydroxypyridine (CDHP: inhibitor dihydroxy pyrimidine dehydroxygenase) and potassium oxonate (inhibitor of phosphoribosyl transferase) plus cisplatin, followed by surgery in patients with locally advanced non-small cell lung cancer.

Proceedings of the 53rd Annual ASTRO Meeting Materials/Methods: From 2005 to 2010, 42 patients staged IIb-IV (UICC 1997) have been treated with concomitant chemoradiotherapy, followed by surgery. Patients characteristics are as follows; male/female = 35/7, median age: 61 years (range: 42 - 77), clinical Stage IIb/IIIa/IIIb/IV = 2/23/14/3, Histology: squamous cell carcinoma/adenocarcinoma/large cell carcinoma/others = 11/3/21/7. Three patients had distant metastases (brain or adrenal glands) which were well controlled by surgery or gamma knife treatment. Chemotherapy consisted of cisplatin (60 mg/m2 on day 1) and TS-1 (orally at 40 mg/m2/dose b.i.d., on days 1 - 14) repeated every 3 weeks for 2 cycles. Beginning on day 1, radiotherapy was started and delivered to the primary tumor and hilar and /or mediastinal lymph nodes. Total dose was 40 - 60 Gy (median: 40Gy) with conventional fraction size 2 Gy. The median treatment period of chemoradiotherapy was 29 days, and the median interval between end of chemoradiotherapy and surgery was 27 days. Twenty-eight patients received adjuvant chemotherapy after surgery. Results: Fifteen of 42 patients received pneumonectomy. Postoperative pathological findings showed that twenty-eight patients (67%) were downstaged. Median follow-up period was 21 months. Overall and disease free survival rate of 4 years were 61.7 % and 49.2 %, respectively. Ten patients with histopathological effects of Ef 3 had 100 % of 4 year overall survival rate compared with patients with Ef 1 - 2 (55.1%) (p = 0.077). Sixteen of 17 patients with recurrence after surgery had distant metastases. No significant difference was found between the overall survival rate of patients with lobectomy and with pneumonectomy (p = 0.34). One patient died of thoracic bleeding after surgery. 13 patients had hematologic adverse event greater than grade 2 after chemoradiotherapy, and five patients had postoperative complication greater than grade 2. Conclusions: Preoperative chemoradiotherapy which combined with cisplatin and TS-1 is an effective treatment option for patients with locally advanced non-small cell lung cancer. Author Disclosure: T. Sasaki: None. S. Uehara: None. M. Abe: None. Y. Shioyama: None. K. Nakamura: None. K. Sugio: None. Y. Ichinose: None. H. Hirata: None. H. Honda: None.


Inter-method Variability of [18F]FDG PET Metabolic Response Assessment of Non-small Cell Lung Cancer (NSCLC)

J. Wang1,2, K. Wong3, K. Frey3, M. Piert3, F. Kong1,4 1 Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, 2Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medial School, Beijing, China, 3Department of Radiology, University of Michigan, Ann Arbor, MI, 4Department of Radiation Oncology, Veteran Administration Hospital, Ann Arbor, MI

Purpose/Objective(s): Standardized uptake values (SUV) are commonly employed for quantitating [18F]FDG PET metabolic tumor response to therapy, despite that it can be affected by multiple confounding factors. Ratios of maximum tumor SUV (SUVTmax) to reference organs such as mediastinum blood pool (MBP) and liver have been applied to minimize the interscan heterogeneity. This study aimed to investigate the variability of the metabolic tumor response assessment in NSCLC evaluated by different SUV normalization methods. Materials/Methods: Patients with Stage I to III NSCLC receiving radiation therapy (RT) were prospectively enrolled into a [18F] FDG PET/CT imaging study. All eligible patients underwent PET/CT scans pre-, during- and post- RT. [18F]FDG PET metabolic response was interpreted by a board certified nuclear medicine physician using measurements of SUVTmax, mean SUV of liver and MBP at the aortic arch. Percentage changes at during and post-RT based on pre-RT SUV levels were calculated for response evaluation. Three methods for assessment of tumor response were determined: 1) absolute SUVTmax, 2) ratio of SUVTmax to MBP (NSUV-A) and 3) ratio to liver (NSUV-L). Data are presented as mean (95% confidence interval). Results: A total of 60 PET-CT scans in 20 consecutive patients were analyzed. The median duration between RT start and duringRT scan was 31 days, and the interval between RT end and post-RT scan was 89 days. The mean SUV of MBP and liver at pre-, during and post RT scan was 1.8 (1.7, 1.9) vs. 2.4 (2.3, 2.6), 1.9 (1.8, 2.0) vs. 2.5 (2.3, 2.7) and 1.9 (1.8, 2.0) vs. 2.4 (2.1, 2.6), respectively. Liver SUV was significantly higher than MBP at all imaging time points (P \ 0.001). Neither SUVof MBP nor liver significantly changed longitudinally. SUVof MBP had less within-patient variation than liver (0.02 vs. 0.11, P = 0.002). The mean reduction at during and post-RT scan of SUVTmax, NSUV-A and NSUV-L were 45% (36%, 55%) vs. 60% (51%, 70%), 47% (37%, 57%) vs. 61% (51%, 71%) and 46% (37%, 55%) vs. 58% (47%, 68%), respectively. The post-RT change in percentage of NSUV-A was statistically higher than that of NSUV-L (P = 0.038). Using 30% reduction as a threshold, the response distribution determined by three methods was statistically consistent (P \ 0.01). Taking during- and post-scans as a whole, intermethod variability for individual response assessment was 17.5% (7/40) including 5 patients at during scans and 2 patients at post scans. Conclusions: Mean SUV measurements of MBP may be more stable than that of liver between serial [18F]FDG PET/CT studies. Metabolic responses determined by different normalization methods are comparable. The best method for response evaluation is yet to be determined. Further studies using pathological response as a reference to identify the optimal evaluation approach are warranted. Author Disclosure: J. Wang: None. K. Wong: None. K. Frey: None. M. Piert: None. F. Kong: None.


Hypofractionated Stereotactic Radiotherapy for Stage III Non-small Cell Lung Cancer: A Dosimetric Feasibility Study

C. Huang1, P. Kupelian1, S. Tenn1, S. Alexander1, C. Lee1, R. Huang2, P. Lee1 1

UCLA, Department of Radiation Oncology, Los Angeles, CA, 2UC Davis, Davis, CA

Purpose/Objective(s): To evaluate the dosimetric feasibility of an aggressive hypofractionated radiotherapy schedule for Stage III non-small cell lung cancers (NSCLC). Materials/Methods: The study sample included 14 cases with Stage III NSCLC. The mean primary tumor size was 5.3 cm (range 1.5 - 10.3). The mean tumor burden (primary and nodal areas) was 111.2 cc (range 9.7 - 424.3 cc). Intended plans consisted of an initial dose of 40 Gy in 10 fractions, followed by a 7 Gy x 5 boost. The clinical target volumes (CTV) consisted of PET avid areas