Dose-dense TPF induction chemotherapy for locally advanced head and neck cancer: a phase II study.

BACKGROUND: Phase 3 studies suggest that induction chemotherapy (ICT) of cisplatin and 5-fluorouracil plus docetaxel (TPF) is effective but toxic for patients with squamous-cell carcinoma of the head and neck (SCCHN). Dose-dense chemotherapy may yield favorable outcomes compared with standard-dose chemotherapy, yet the optimal induction regimen remains undefined. We assessed the efficacy and tolerability of biweekly dose-dense TPF ICT in patients with SCCHN. METHODS: In this prospective phase II study, We enrolled patients with stage III/IV (AJCC 7th edition) unresectable squamous cell carcinoma of head and neck cancer. Patients received dose-dense TPF (ddTPF) with cisplatin and docetaxel 50 mg/m2 on day 1, leucovorin 250 mg/m2 on day1, followed by 48-h continuous infusion of 2500 mg/m2 of 5-fluorouracil on day 1 and 2, every 2 weeks for 6 cycles followed by radiotherapy. The primary endpoint was the response rate (RR) after ICT. RESULTS: Fifty-eight patients were enrolled from June 2014 to September 2015. Overall RR after ICT was 89.6% [complete response (CR), 31%; partial response (PR), 58.6%]. Grade 3/4 neutropenia, mucositis, and diarrhea incidences were 25.9, 1.7, and 1.7%, respectively. 94.8% of patients completed all treatment courses of ICT without dose reduction. The 3-year overall survival (OS) was 54.3% (95%CI: 39.7 to 66.8%) and progression-free survival (PFS) was 34.3% (95%CI: 22.0 to 46.9%). Multivariate analysis showed that CR after ICT is an independent prognostic factor for OS and PFS. CONCLUSIONS: Six cycles of ddTPF is an active, well-tolerated induction regimen for patients with SCCHN. The presence of CR after ICT predicted long-term survival. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04397341 , May 21, 2020, retrospectively registered.

Clinical Outcomes and Prognostic Factors of Patients With Esophageal Squamous Cell Carcinoma With Oligo-recurrence Treated With Radical Re-irradiation.

BACKGROUND: For patients with esophageal squamous cell carcinoma (ESCC) with oligo-recurrence (OR) after previous curative radiotherapy and not eligible for radical resection, the role of radical re-irradiation was not clear. Therefore, we aimed to investigate the outcome and prognostic factors of such patients. PATIENTS AND METHODS: We identified patients with OR of ESCC after previous curative radiotherapy and were treated with radical re-irradiation within 2012-2018 via an in-house prospectively established database. The characteristics of patients, disease, treatment, and outcome were retrospectively obtained via chart review. The first day of re-irradiation was defined as the index date. Overall survival was calculated via the Kaplan-Meier method. Log-rank test was used for univariate analysis and Cox regression method was used for multivariable analysis. RESULTS: We identified thirty patients for analyses. After a median follow-up of 9 (range=2-76) months, the 5-year overall survival rate was 21%. Four patients with possible radiotherapy-related complication in need of inpatient care were identified. Gross tumor volume was the only significant prognostic factor in both univariate and multivariable analyses. CONCLUSION: We found that radical definitive re-irradiation may lead to one-fifth long-term survivors of patients with OR after previous curative radiotherapy for ESCC, and the gross tumor volume was the only significant prognostic factor for these patients. Randomized controlled trials should be considered to compare radical re-irradiation with the current standard of care (systemic therapy) for this population.

Effectiveness of tomotherapy vs linear accelerator image-guided intensity-modulated radiotherapy for localized pharyngeal cancer treated with definitive concurrent chemoradiotherapy: a Taiwanese population-based propensity score-matched analysis.

OBJECTIVE: This study used a population-based propensity score (PS)-matched analysis to compare the effectiveness of tomotherapy-based image-guided intensity-modulated radiotherapy (referred to as T-IMRT) with that of linear accelerator based (referred to as L-IMRT) for clinically localized pharyngeal cancer (LPC, divided into nasopharyngeal cancer and non-nasopharyngeal cancer) with definitive concurrent chemoradiotherapy (CCRT). METHODS: Eligible LPC patients diagnosed between 2007 and 2014 were identified among all citizens in Taiwan from the Health and Welfare Data Science Center database. A PS-matched sample based on the PS estimated from the covariables of interest was constructed to compare the effectiveness of T-IMRT with L-IMRT. In the primary analysis, overall survival (OS) was compared for assessment of effectiveness. We also evaluated freedom from local regional recurrence and pharyngeal cancer-specific survival and performed supplementary analyses. RESULTS: The study population included 960 patients equally divided into two groups. OS did not differ significantly between the T-IMRT and L-IMRT groups (hazard ratio for death: 0.82, p = 0.15, 5-year OS rate: 79 and 74% for T-IMRT and L-IMRT, respectively), and there were no significant differences in the other endpoints or supplementary analyses. CONCLUSION: For LPC patients treated with definitive CCRT, we found no significant difference in disease control or survival between the T-IMRT and L-IMRT groups. However, further studies, especially randomized trials or studies focusing on other dimensions, such as quality of life, are needed. Advances in knowledge: We provide the first population-based study, as well as the largest study, on the clinical effectiveness of T-IMRT compared with L-IMRT in conjunction with CCRT in LPC patients.

Chemotherapy alone is an alternative treatment in treating localized primary ocular adnexal lymphomas.

This study investigated the treatment efficacy and long-term adverse effects of various treatment modalities for primary ocular adnexal lymphomas (POALs). We retrospectively reviewed 107 patients who received first-line chemotherapy, radiotherapy, and other treatment modalities from 1990 to 2015. Nighty-three (87%) patients were diagnosed with mucosa-associated lymphoid tissue (MALT) lymphoma, with the orbit being the most common site (49 patients, 46%). Among 91 patients with stage I-IIE1 disease, 26 underwent chemotherapy, 34 underwent radiotherapy, and 31 received other treatment modalities. For chemotherapy, radiotherapy, and other treatment modalities, the 5-year event-free survival (EFS) rates were 90.0%, 89.7%, and 85.8% and the 5-year overall survival (OS) rates were 100%, 90.4%, and 87.5%, respectively. Moreover, among 80 patients with stage I-IIE1 MALT lymphoma, the complete remission, 5-year EFS and OS rates were not significantly different between patients receiving chemotherapy and those receiving radiotherapy. Among 16 patients with stage IIE2-IVE disease, the 5-year EFS rates for chemotherapy alone (n = 11) and combined radiotherapy and chemotherapy (n = 5) were 61.7% and 80%, respectively, whereas the 5-year OS rate for both groups was 80.0%. Neutropenia (15.2%) was the most common side effect in patients who received chemotherapy, whereas cataract (16.3%) was the most common late sequela in patients who received radiotherapy. Multivariate analysis revealed that old age (> 60 y) and an advanced stage (stage III/IV) were prognostic factors for poor OS. Our results indicate that chemotherapy yields satisfactory disease control and fewer side effects, and acts as an alternative therapy for patients with localized POALs.

Immunohistochemical biomarkers and volumetric parameters for predicting radiotherapy-based outcomes in patients with p16-negative pharyngeal cancer.

BACKGROUND: This study determined the prognostic effects of immunohistochemical biomarkers and volumetric parameters predicting radiotherapy-based treatment in patients with p16-negative squamous cell carcinoma of the oropharynx or hypopharynx. RESULTS: VEGF immunoreactivity > 2 and GLUT1 overexpression were prognostic factors for lower cause-specific survival. Moreover, both factors were associated with lower disease-free survival. The predictors of lower primary relapse-free survival were VEGF immunoreactivity > 2 and CT-based gross tumor volume > 16 mL. MATERIALS AND METHODS: Immunohistochemical biomarkers in pretreatment biopsy specimens from 60 patients with p16-negative cancer were analyzed using tissue microarrays. Computed tomography (CT)-based and biological tumor volumes were retrieved through fluorodeoxyglucose positron emission tomography-CT. Correlations of cause-specific, disease-free, and primary relapse-free survival with volumetric parameters and the immunohistochemical biomarker score were investigated. CONCLUSIONS: For patients with p16-negative pharyngeal cancer receiving radiotherapy, treatment outcomes can be stratified by VEGF and GLUT1 expression and CT-based gross tumor volume.

Immunohistochemical overexpression of hypoxia-induced factor 1α associated with slow reduction in 18fluoro-2-deoxy-D-glucose uptake for chemoradiotherapy in patients with pharyngeal cancer.

BACKGROUND: This study examined genomic factors associated with a reduction in 18fluoro-2-deoxy-D-glucose (FDG) uptake during positron emission tomography-computed tomography (PET-CT) for definitive chemoradiotherapy (CRT) in patients with pharyngeal cancer. METHODS: The pretreatment and interim PET-CT images of 25 patients with advanced pharyngeal cancers receiving definitive CRT were prospectively evaluated. The maximum standardized uptake value (SUVmax) of the interim PET-CT and the reduction ratio of the SUVmax (SRR) between the two images were measured. Genomic data from pretreatment incisional biopsy specimens (SLC2A1, CAIX, VEGF, HIF1A, BCL2, Claudin-4, YAP1, MET, MKI67, and EGFR) were analyzed using tissue microarrays. Differences in FDG uptake and SRRs between tumors with low and high gene expression were examined using the Mann-Whitney test. Cox regression analysis was performed to examine the effects of variables on local control. RESULTS: The SRR of the primary tumors (SRR-P) was 0.59 ± 0.31, whereas the SRR of metastatic lymph nodes (SRR-N) was 0.54 ± 0.32. Overexpression of HIF1A was associated with a high iSUVmax of the primary tumor (P < 0.001) and neck lymph node (P = 0.04) and a low SRR-P (P = 0.02). Multivariate analysis revealed that patients who had tumors with low SRR-P or high HIF1A expression levels showed inferior local control. CONCLUSION: In patients with pharyngeal cancer requiring CRT, HIF1A overexpression was positively associated with high interim SUVmax or a slow reduction in FDG uptake. Prospective trials are needed to determine whether the local control rate can be stratified using the HIF1A level as a biomarker and SRR-P.

Early radiation-induced liver toxicities are associated with poor survival in patients with advanced hepatocellular carcinoma.

AIM: Little is known about the impact of radiotherapy associated early hepatic toxicities. This study is to investigate the risk factors and outcome of early radiation-induced liver disease (early-RILD) in patients with hepatocellular carcinoma. METHODS: One hundred patients with advanced hepatocellular carcinoma receiving hepatic radiotherapy were included in this retrospective analysis. All had no evidence of intrahepatic tumor progression within 3 months after initiating radiotherapy. The toxicities were graded according to the Common Terminology Criteria for adverse events version 4.0. Early-RILD was defined as any detectable events of RILD occurring during or within 2 weeks after the ending of radiotherapy. Patient- and radiotherapy-related data, and several staging/scoring parameters were retrieved for analysis. Logistic regression analysis was used to find risk factors for early-RILD. Cox regression model was performed to explore prognosticators for survival. RESULTS: Child-Turcotte-Pugh (CTP) score >5 was the predictor for early-RILD (odds ratio 5.38, P = 0.004). The incidence of early-RILD in patients with CTP scores 6/7 and 5 was 34% and 13.2%, respectively. Early-RILD and a Cancer of the Liver Italian Program (CLIP) score > 2 were the two prognostic factors associated with inferior overall survival (hazard ratio 2.79, P = 0.04; hazard ratio = 3.79, P = 0.04, respectively). The median overall survival for patients with early-RILD was 3.5 months compared with 12.7 months in those without this event. CONCLUSION: The occurrence of early-RILD is associated with high mortality. A CTP score >5 is the most informative factor predicting early-RILD.

Risk stratification of metastatic neck nodes by CT and PET in patients with head and neck cancer receiving definitive radiotherapy.

UNLABELLED: The aim of this study was to investigate the prognostic impact of CT and (18)F-FDG PET/CT on the outcome of metastatic neck node (MNN) in patients with head and neck cancer receiving definitive radiotherapy or chemoradiotherapy. METHODS: This patient-based study included 91 patients diagnosed with pharyngeal cancers with MNN (N1, 15; N2, 70; N3, 6). All had pretreatment CT and PET/CT before definitive chemoradiotherapy/radiotherapy. Parameters of MNNs for each patient, including maximal diameter, nodal volume, radiologic central necrosis, maximum standardized uptake value, metabolic tumor volume, and total lesion glycolysis (TLG), were retrieved for the analysis. Nodal relapse-free survival (NRFS) and survivals were calculated using the Kaplan-Meier method. Independent predictors were identified using Cox regression analysis. RESULTS: After a median follow-up of 18 mo, 64 patients remained nodal relapse-free, and 27 experienced neck recurrence. Multivariate analysis showed that the application of 40% of the maximal uptake of nodal TLG (N-TLG40%) 38 g or greater (P = 0.03; hazard ratio, 2.63; 95% confidence interval, 1.10-6.30) and radiologic necrosis on CT scan (P = 0.001; hazard ratio, 10.99; 95% confidence interval, 2.56-47.62) were 2 adverse features for NRFS. Patients who had an N-TLG40% 38 g or greater and central radiologic necrosis had a significantly inferior 2-y NRFS (53% vs. 77% and 45% vs. 95%, respectively). CONCLUSION: The outcome of MNNs in patients with head and neck cancer receiving chemoradiotherapy/radiotherapy can be predicted according to radiologic necrosis and N-TLG40% value. The 2 adverse features should be validated in future trials. In this way, patients can be treated alternatively or aggressively.

Motion freeze for respiration motion correction in PET/CT: a preliminary investigation with lung cancer patient data.

PURPOSE: Respiratory motion presents significant challenges for accurate PET/CT. It often introduces apparent increase of lesion size, reduction of measured standardized uptake value (SUV), and the mismatch in PET/CT fusion images. In this study, we developed the motion freeze method to use 100% of the counts collected by recombining the counts acquired from all phases of gated PET data into a single 3D PET data, with correction of respiration by deformable image registration. METHODS: Six patients with diagnosis of lung cancer confirmed by oncologists were recruited. PET/CT scans were performed with Discovery STE system. The 4D PET/CT with the Varian real-time position management for respiratory motion tracking was followed by a clinical 3D PET/CT scan procedure in the static mode. Motion freeze applies the deformation matrices calculated by optical flow method to generate a single 3D effective PET image using the data from all the 4D PET phases. RESULTS: The increase in SUV and decrease in tumor size with motion freeze for all lesions compared to the results from 3D and 4D was observed in the preliminary data of lung cancer patients. In addition, motion freeze substantially reduced tumor mismatch between the CT image and the corresponding PET images. CONCLUSION: Motion freeze integrating 100% of the PET counts has the potential to eliminate the influences induced by respiratory motion in PET data.

A population-based study of primary chemoradiotherapy in clinical stage III non-small cell lung cancer: intensity-modulated radiotherapy versus 3D conformal radiotherapy.

AIM: To compare the effectiveness of intensity-modulated radiotherapy (IMRT) vs. 3D conformal radiotherapy (3DCRT) for clinical stage III non-small cell lung cancer (NSCLC) treated with primary chemoradiotherapy via a population-based retrospective cohort analysis. PATIENTS AND METHODS: Using the Collaboration Center of Health Information Application (CCHIA) database, we identified 99 patients with stage III NSCLC treated with primary chemoradiotherapy from 2007 to 2009, with complete data available for analysis. We compared the risk of death within two years of diagnosis and the hazard ratio for death between those treated with IMRT and those with 3DCRT. Univariate and multivariate analyses were conducted to determine the efficacy of IMRT and 3DCRT. Sensitivity analyses were also conducted to assess relationships in the various subgroups. RESULTS: The risk of death within two years of diagnosis was similar for IMRT and 3DCRT (36% vs. 37%, p=0.97). For the entire follow-up period, the probability of death was not statistically different when IMRT was compared to 3DCRT (p=0.8). On multivariate analysis, the adjusted hazard ratio of death was statistically insignificantly higher for IMRT vs. 3DCRT (hazard ratio of death=1.54, 95% confidence interval=0.82-2.91, p=0.18). The results remained similar in the sensitivity analyses. CONCLUSION: Our population-based analysis from CCHIA suggests that for patients with clinical stage III NSCLC treated with primary chemoradiotherapy, the survival outcome of those treated with IMRT was not superior to those treated with 3DCRT. Further prospective studies and cost-effectiveness analyses are warranted.

Interim FDG PET/CT for predicting the outcome in patients with head and neck cancer.

OBJECTIVES/HYPOTHESIS: The study aimed to investigate the prognostic effects of interim (18) fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (PET/CT) during definitive radiotherapy (RT) or chemoradiotherapy (CRT) in patients with head and neck cancer. STUDY DESIGN: This is a prospectively treatment study. METHODS: The pretreatment and interim PET/CT images of 51 patients with advanced pharyngeal cancers receiving definitive RT/CRT were evaluated prospectively. The interim PET/CT images were taken at a cumulative RT dose ranging from 41.4 to 46.8 Gy. The maximum standardized uptake value (SUVm) of the interim PET/CT and the reduction ratio of the SUVm (SRR) between the two images were measured. The differences between patients with or without local failures were examined using the Mann-Whitney test. Overall survival (OS), disease-free survival (DFS), and primary and nodal relapse-free survival rates were calculated using the Kaplan-Meier method. Independent prognosticators were identified using Cox regression analysis. RESULTS: After a median follow-up duration of 23 months, a higher interim SUVm was associated with local failures. Conducting a multivariate analysis revealed that a SUVmax reduction ratio of primary tumor (SRR-P) < 0.64 was associated with the inferior OS (hazard ratio 2.64; P =0.035) and DFS (hazard ratio 2.33; P = 0.045). Patients who had tumors with an SRR-P < 0.64 had a considerably lower 2-year OS and DFS compared with those who had SRR-P ≥ 0.64 (47% vs. 66%; 41% vs. 64%). CONCLUSION: A higher interim SUVm was associated with local recurrence. In addition, patients with a lower SRR-P should be considered to be at risk of primary failure. LEVEL OF EVIDENCE: 4.

Respiratory motion reduction in PET/CT using abdominal compression for lung cancer patients.

PURPOSE: Respiratory motion causes substantial artifacts in reconstructed PET images when using helical CT as the attenuation map in PET/CT imaging. In this study, we aimed to reduce the respiratory artifacts in PET/CT images of patients with lung tumors using an abdominal compression device. METHODS: Twelve patients with lung cancer located in the middle or lower lobe of the lung were recruited. The patients were injected with 370 MBq of 18F-FDG. During PET, the patients assumed two bed positions for 1.5 min/bed. After conducting free-breathing imaging, we obtained images of the patients with abdominal compression by applying the same setup used in the free-breathing scan. The differences in the standardized uptake value (SUV)max, SUVmean, tumor volume, and the centroid of the tumors between PET and various CT schemes were measured. RESULTS: The SUVmax and SUVmean derived from PET/CT imaging using an abdominal compression device increased for all the lesions, compared with those obtained using the conventional approach. The percentage increases were 18.1% ±14% and 17% ±16.8% for SUVmax and SUVmean, respectively. PET/CT imaging combined with abdominal compression generally reduced the tumor mismatch between CT and the corresponding attenuation corrected PET images, with an average decrease of 1.9±1.7 mm over all the cases. CONCLUSIONS: PET/CT imaging combined with abdominal compression reduces respiratory artifacts and PET/CT misregistration, and enhances quantitative SUV in tumor. Abdominal compression is easy to set up and is an effective method used in PET/CT imaging for clinical oncology, especially in the thoracic region.

Impact of body-mass factors on setup displacement in patients with head and neck cancer treated with radiotherapy using daily on-line image guidance.

BACKGROUND: To determine the impact of body-mass factors (BMF) before radiotherapy and changes during radiotherapy on the magnitude of setup displacement in patients with head and neck cancer (HNC). METHODS: The clinical data of 30 patients with HNC was analyzed using the alignment data from daily on-line on-board imaging from image-guided radiotherapy. BMFs included body weight, body height, and the circumference and bilateral thickness of the neck. Changes in the BMFs during treatment were retrieved from cone beam computed tomography at the 10th and 20th fractions. Setup errors for each patient were assessed by systematic error (SE) and random error (RE) through the superior-inferior (SI), anterior-posterior (AP), and medial-lateral (ML) directions, and couch rotation (CR). Using the median values of the BMFs as a cutoff, the impact of the factors on the magnitude of displacement was assessed by the Mann-Whitney U test. RESULTS: A higher body weight before radiotherapy correlated with a greater AP-SE (p = 0.045), SI-RE (p = 0.023), and CR-SE (p = 0.033). A longer body height was associated with a greater SI-RE (p = 0.002). A performance status score of 1 or 2 was related to a greater AP-SE (p = 0.043), AP-RE (p = 0.015), and SI-RE (p = 0.043). Among the ratios of the BMFs during radiotherapy, the values at the level of mastoid tip at the 20th fraction were associated with greater setup errors. CONCLUSIONS: To reduce setup errors in patients with HNC receiving RT, the use of on-line image-guided radiotherapy is recommended for patients with a large body weight or height, and a performance status score of 1-2. In addition, adaptive planning should be considered for those who have a large reduction ratio in the circumference (<1) and thickness (<0.94) over the level of the mastoid tip during the 20th fraction of treatment.

Thoracic tumor volume delineation in 4D-PET/CT by low dose interpolated CT for attenuation correction.

PURPOSE: 4D-PET/CT imaging is an excellent solution for reducing the breathing-induced effects in both CT and PET images. In 4D-PET/CT, 4D-CT images are selected to match those of 4D-PET phase by phase and the corresponding phases are used for attenuation correction in 4D-PET. However, the high radiation dose that patients acquire while undergoing 4D-CT imaging for diagnostic purposes remains a concern. This study aims to assess low-dose interpolated CT (ICT) for PET attenuation correction (PETICT) in thoracic tumor volume delineation. METHODS AND MATERIALS: Twelve thoracic cancer patients (10 esophageal and 2 lung cancer cases) were recruited. All patients underwent 4D-PET/CT scans. The optical flow method based on image intensity gradient was applied to calculate the motion displacement in three dimensions for each voxel on two original extreme CT phases in the respiratory cycle, end-inspiration and end-expiration. The interpolated CTs were generated from two phases of the original 4D-CT using motion displacement. RESULTS: Tumor motion due to respiration was estimated in the anterior-posterior dimension, the lateral dimension and the superior-inferior dimension by the optical flow method. The PETICT and ICT (4D-PET ICT/ICT) matched each other spatially in all the phases. The distortion of tumor shape and size resulting from respiratory motion artifacts were not observed in 4D-PETICT. The tumor volume measured by 4D-PET ICT/ICT correlated to the tumor volume measured by 4D-PET/CT (p = 0.98). CONCLUSIONS: 4D-PETICT consistently represented the interpretation of FDG uptake as effectively as 4D-PET. 4D-PET ICT/ICT is a low-dose alternative to 4D-CT and significantly improves the interpretation of PET and CT images, while solving the respiratory motion problem as effectively as 4D-PET/CT.

Radiotherapy for esophageal cancer using simultaneous integrated boost techniques: dosimetric comparison of helical TomoTherapy, Volumetric-modulated Arc Therapy (RapidArc) and dynamic intensity-modulated radiotherapy.

This study compared TomoTherapy (TM), with Volumetric-Modulated Arc Therapy (RapidArc, RA), and dynamic intensity-modulated radiotherapy (dIMRT) for locally advanced esophageal cancer (LAEC) with a simultaneous integrated boost (SIB) technique with regard to the target coverage and sparing of organs at risk (OARs). Twelve patients receiving four-dimensional computed tomography simulation were enrolled for dosimetric comparison. Gross tumor volume was contoured with the maximum intensity projection method. Using an SIB method, Planning target volume low (PTVL) and planning target volume high (PTVH) were prescribed as 54 Gy and 60 Gy, respectively, each administered in 30 fractions. We compared the results of statistical analysis for target coverage, homogeneity index (HI) and conformity index (CI) of PTVs, parameters of OARs and monitor unit (MU) were compared for analysis. The HI for PTVH varied significantly for the 3 techniques of TM, RA, and dIMRT (4.38 ± 0.86, 6.40 ± 0.86, and 6.11 ± 0.68, respectively; P , 0.001). The CI scores for PTVH also differed across TM, RA, and dIMRT (0.64 6 0.06, 0.53 6 0.06, and 0.59 ± 0.05, respectively; P < 0.001). The HI for PTVL showed a significant difference among TM, RA, and dIMRT (15.44 ± 0.88, 20.88 ± 1.03 and 18.65 ± 1.42, respectively; P < 0.001). The percentage of lung volume receiving 5 Gy (V5) and 20 Gy (V20) (for V5: TM 54.4 ± 8.0%; RA 67.5 ± 14.5%, P < 0.01; dIMRT 44.8 ± 8.2%; for V20: 13.6 6 3.3%, 12.2 ± 3.6%, 18.1 6 3.4%, P = 0.001, respectively). For RA, the lung V5 ≥ 65% was observed in 6 patients and the V10 ≥ 50 % in one patient. TM, RA and dIMRT provided comparable coverage of the target and sparing of OARs. TM demonstrated superior CI and HI for tumor coverage and lowered the specified dose parameters for lung. RA provided an advantage in terms of the lowest MU and V20 of the lung, but its higher lung V5 was of some concern about lung toxicity.

Improvement of internal tumor volumes of non-small cell lung cancer patients for radiation treatment planning using interpolated average CT in PET/CT.

Respiratory motion causes uncertainties in tumor edges on either computed tomography (CT) or positron emission tomography (PET) images and causes misalignment when registering PET and CT images. This phenomenon may cause radiation oncologists to delineate tumor volume inaccurately in radiotherapy treatment planning. The purpose of this study was to analyze radiology applications using interpolated average CT (IACT) as attenuation correction (AC) to diminish the occurrence of this scenario. Thirteen non-small cell lung cancer patients were recruited for the present comparison study. Each patient had full-inspiration, full-expiration CT images and free breathing PET images by an integrated PET/CT scan. IACT for AC in PET(IACT) was used to reduce the PET/CT misalignment. The standardized uptake value (SUV) correction with a low radiation dose was applied, and its tumor volume delineation was compared to those from HCT/PET(HCT). The misalignment between the PET(IACT) and IACT was reduced when compared to the difference between PET(HCT) and HCT. The range of tumor motion was from 4 to 17 mm in the patient cohort. For HCT and PET(HCT), correction was from 72% to 91%, while for IACT and PET(IACT), correction was from 73% to 93% (*p<0.0001). The maximum and minimum differences in SUVmax were 0.18% and 27.27% for PET(HCT) and PET(IACT), respectively. The largest percentage differences in the tumor volumes between HCT/PET and IACT/PET were observed in tumors located in the lowest lobe of the lung. Internal tumor volume defined by functional information using IACT/PET(IACT) fusion images for lung cancer would reduce the inaccuracy of tumor delineation in radiation therapy planning.

Deformation effect on SUVmax changes in thoracic tumors using 4-D PET/CT scan.

Respiratory motion blurs the standardized uptake value (SUV) and leads to a further signal reduction and changes in the SUV maxima. 4D PET can provide accurate tumor localization as a function of the respiratory phase in PET/CT imaging. We investigated thoracic tumor motion by respiratory 4D CT and assessed its deformation effect on the SUV changes in 4D PET imaging using clinical patient data. Twelve radiation oncology patients with thoracic cancer, including five lung cancer patients and seven esophageal cancer patients, were recruited to the present study. The 4D CT and PET image sets were acquired and reconstructed for 10 respiratory phases across the whole respiratory cycle. The optical flow method was applied to the 4D CT data to calculate the maximum displacements of the tumor motion in respiration. Our results show that increased tumor motion has a significant degree of association with the SUVmax loss for lung cancer. The results also show that the SUVmax loss has a higher correlation with tumors located at lower lobe of lung or at lower regions of esophagus.

Consistently lower narcotics consumption after video-assisted thoracoscopic surgery for early stage non-small cell lung cancer when compared to open surgery: a one-year follow-up study.

OBJECTIVES: Video-assisted thoracoscopic surgery (VATS) is possibly associated with reduced acute pain and narcotics consumption when compared to open surgery, but little is known about the long-term effect. The goal of our study was to evaluate whether narcotics consumption is consistently lower after VATS for early stage non-small cell lung cancer (NSCLC), as compared to open surgery, during one-year follow-up. METHODS: This nationwide retrospective cohort study was conducted using data relating to cancer registry and national compulsory comprehensive claims in Taiwan. Our study cases were those newly diagnosed with clinical Stage I NSCLC, who underwent primary lung resection in the year 2007. The date of the admission during which index surgery was performed was used as the index date. We compared the use of narcotics, between the VATS and open surgery groups, over a period of one year following the index date. We defined narcotics as either Level 1 or 2 drugs as regulated in Taiwan. We also used an equiananalgesic dose chart to convert drug consumption into a uniform narcotics equivalent dose. Chi-square and t-tests were used for statistical analysis. RESULTS: We identified 329 cases (114 for VATS and 215 for open surgery). These two groups were balanced for most clinical variables. VATS was associated with lower narcotics consumption during the index admission (mean equivalent dose of intravenous morphine: 54.6 vs 71.4 mg) and this trend extended to the period covering the 2nd to 12th month after index date (73.8 vs 149.5mg). CONCLUSIONS: Narcotics consumption is consistently lower after VATS for early stage NSCLC, as compared to open surgery. Further prospective studies would be of great value in validating this finding.

The clinical application of 4D 18F-FDG PET/CT on gross tumor volume delineation for radiotherapy planning in esophageal squamous cell cancer.

A combination of four-dimensional computed tomography with (18)F-fluorodeoxyglucose positron emission tomography (4D CT-FDG PET) was used to delineate gross tumor volume (GTV) in esophageal cancer (EC). Eighteen patients with EC were prospectively enrolled. Using 4D images taken during the respiratory cycle, the average CT image phase was fused with the average FDG PET phase in order to analyze the optimal standardized uptake values (SUV) or threshold. PET-based GTV (GTV(PET)) was determined with eight different threshold methods using the auto-contouring function on the PET workstation. The difference in volume ratio (VR) and conformality index (CI) between GTV(PET) and CT-based GTV (GTV(CT)) was investigated. The image sets via automatic co-registrations of 4D CT-FDG PET were available for 12 patients with 13 GTV(CT) values. The decision coefficient (R(2)) of tumor length difference at the threshold levels of SUV 2.5, SUV 20% and SUV 25% were 0.79, 0.65 and 0.54, respectively. The mean volume of GTV(CT) was 29.41 ± 19.14 ml. The mean VR ranged from 0.30 to 1.48. The optimal VR of 0.98, close to 1, was at SUV 20% or SUV 2.5. The mean CI ranged from 0.28 to 0.58. The best CI was at SUV 20% (0.58) or SUV 2.5 (0.57). The auto-contouring function of the SUV threshold has the potential to assist in contouring the GTV. The SUV threshold setting of SUV 20% or SUV 2.5 achieves the optimal correlation of tumor length, VR, and CI using 4D-PET/CT images.

Pretreatment maximal standardized uptake value of the primary tumor predicts outcome to radiotherapy in patients with pharyngeal cancer.

This study aimed to investigate whether the combination of clinical information, tumor volume and pretreatment SUVmax at the primary tumors might improve the prognostic stratification in pharyngeal cancer (PC) patients treated with radiotherapy (RT). Sixty-two patients with PC (35 oropharynx; 27 hypopharynx) treated with RT were enrolled in this retrospective analysis. All patients received pretreatment FDG- PET or PET/CT. The primary tumor relapse-free survival (PRFS) was calculated according to different variables. The median values of the SUVmax for the primary tumors (SUVp-max) and the gross tumor volume (GTVp) were used to divide patients into two groups. Independent prognosticators were identified by the Cox regression analysis. In this study, the median SUVp-max and GTVp was 11 and 15.5 ml. Patients having tumors with SUVp-max > 11 had a significantly inferior 2-year PRFS (41% vs. 75%, p = 0.003) compared with patients having lower uptake tumors. Multivariate analysis of the PRFS showed two prognostic factors: SUVp-max > 11 (p = 0.04, hazard ratio = 2.67) and GTVp > 15.5 ml (p = 0.03, hazard ratio = 2.88). For patients with a GTVp less than 15.5 ml, there was a more significant impact of SUVmax-p on their PRFS compared to that for those with large ones. We disclosed a higher pretreatment SUVp-max is a predictor for primary recurrence in PC patients treated with RT, particularly for those with smaller tumor volumes. Patients with a large tumor volume or a higher SUVp-max should be considered for requiring more aggressive treatment approaches.