Shang Wen Chen

Phase 2 study of combined sorafenib and radiation therapy in patients with advanced hepatocellular carcinoma

PURPOSE This phase 2 study evaluated the efficacy of radiation therapy (RT) with concurrent and sequential sorafenib therapy in patients with unresectable hepatocellular carcinoma (HCC). METHODS AND MATERIALS Forty patients with unresectable HCC unfit for transarterial chemoembolization were treated with RT with concurrent and sequential sorafenib. Sorafenib was administered from the commencement of RT at a dose of 400 mg twice daily and continued to clinical or radiologic progression, unacceptable adverse events, or death. All patients had underlying Child-Pugh A cirrhosis. The maximal tumor diameter ranged from 3.0 cm to 15.5 cm. Coexisting portal vein thrombosis was found in 24 patients and was irradiated simultaneously. The cumulative RT dose ranged from 40 Gy to 60 Gy (median, 50 Gy). Image studies were done 1 month after RT and then every 3 months thereafter. RESULTS Thirty-three (83%) completed the allocated RT. During RT, the incidence of hand-foot skin reactions ≥ grade 2 and diarrhea were 37.5% and 25%, respectively, and 35% of patients had hepatic toxicities grade ≥2. Twenty-two (55.0%) patients achieved complete or partial remission at the initial assessment, and 18 (45%) had stable or progressive disease. The 2-year overall survival and infield progression-free survival (IFPS) were 32% and 39%, respectively. A Cancer of the Liver Italian Program (CLIP) score ≥2 was associated with an inferior outcome in overall survival. Six patients (15%) developed treatment-related hepatic toxicity grade ≥3 during the sequential phase, and 3 of them were fatal. CONCLUSIONS When RT and sorafenib therapy were combined in patients with unresectable HCC, the initial complete or partial response rate was 55% with a 2-year IFPS of 39%. A CLIP score ≥2 was associated with an inferior outcome in overall survival. Hepatic toxicities are a major determinant of the safety; the combination should be used with caution and needs further investigation.

Prognostic impact of tumor volume in patients with stage III-IVA hypopharyngeal cancer without bulky lymph nodes treated with definitive concurrent chemoradiotherapy.

To investigate the prognostic value of volumetric analysis in patients with stage III–IVA hypopharyngeal cancer treated with concurrent chemoradiotherapy (CCRT).

18F-FDG PET/CT-based gross tumor volume definition for radiotherapy in head and neck Cancer: a correlation study between suitable uptake value threshold and tumor parameters

BackgroundTo define a suitable threshold setting for gross tumor volume (GTV) when using 18Fluoro-deoxyglucose positron emission tomography and computed tomogram (PET/CT) for radiotherapy planning in head and neck cancer (HNC).MethodsFifteen HNC patients prospectively received PET/CT simulation for their radiation treatment planning. Biological target volume (BTV) was derived from PET/CT-based GTV of the primary tumor. The BTVs were defined as the isodensity volumes when adjusting different percentage of the maximal standardized uptake value (SUVmax), excluding any artifact from surrounding normal tissues. CT-based primary GTV (C-pGTV) that had been previously defined by radiation oncologists was compared with the BTV. Suitable threshold level (sTL) could be determined when BTV value and its morphology using a certain threshold level was observed to be the best fitness of the C-pGTV. Suitable standardized uptake value (sSUV) was calculated as the sTL multiplied by the SUVmax.ResultsOur result demonstrated no single sTL or sSUV method could achieve an optimized volumetric match with the C-pGTV. The sTL was 13% to 27% (mean, 19%), whereas the sSUV was 1.64 to 3.98 (mean, 2.46). The sTL was inversely correlated with the SUVmax [sTL = -0.1004 Ln (SUVmax) + 0.4464; R2 = 0.81]. The sSUV showed a linear correlation with the SUVmax (sSUV = 0.0842 SUVmax + 1.248; R2 = 0.89). The sTL was not associated with the value of C-pGTVs.ConclusionIn PET/CT-based BTV for HNC, a suitable threshold or SUV level can be established by correlating with SUVmax rather than using a fixed threshold.

Value of computed tomography-based tumor volume as a predictor of outcomes in hypopharyngeal cancer after treatment with definitive radiotherapy

Objectives: To investigate the value of pretreatment computed tomography (CT) volumetric analysis for the prediction of treatment outcome in patients with hypopharyngeal cancer (HPC) treated by definitive radiotherapy (RT).

CLINICAL IMPLICATIONS OF THE TUMOR VOLUME REDUCTION RATE IN HEAD-AND-NECK CANCER DURING DEFINITIVE INTENSITY-MODULATED RADIOTHERAPY FOR ORGAN PRESERVATION

PURPOSE To investigate the prognostic value of the volume reduction rate (VRR) in patients with head-and-neck cancer treated with intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS Seventy-six patients with oropharyngeal cancer (OPC) and another 76 with hypopharyngeal cancer (HPC) were enrolled in volumetric analysis. All patients received allocated radiotherapy courses. Adaptive computed tomography was done 4 to 5 weeks after the start of IMRT. Primary tumor volume measurement was derived using separate images for the pretreatment gross tumor volume (pGTV) and the interval gross tumor volume. RESULTS In the OPC group, the pGTV ranged from 6.6 to 242.6 mL (mean, 49.9 mL), whereas the value of the VRR ranged from 0.014 to 0.74 (mean, 0.43). In HPC patients, the pGTV ranged from 4.1 to 152.4 mL (mean, 35.6 mL), whereas the VRR ranged from -1.15 to 0.79 (mean, 0.33). Multivariate analysis of the primary tumor relapse-free survival for OPC revealed three prognostic factors: T4 tumor (p = 0.0001, hazard ratio 7.38), pGTV ≥20 mL (p = 0.01, hazard ratio 10.61), and VRR <0.5 (p = 0.001, hazard ratio 6.49). Multivariate analysis of the primary tumor relapse-free survival for HPC showed two prognostic factors: pGTV ≥30 mL (p = 0.001, hazard ratio 2.87) and VRR <0.5 (p = 0.03, hazard ratio 2.25). CONCLUSION The VRR is an outcome predictor for local control in OPC and HPC patients treated with IMRT. Those with large tumor volumes or a VRR <0.5 should be considered for a salvage operation or a dose-escalation scheme.

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 18F-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 (GTVPET) 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 GTVPET and CT-based GTV (GTVCT) was investigated. The image sets via automatic co-registrations of 4D CT-FDG PET were available for 12 patients with 13 GTVCT values. The decision coefficient (R2) 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 GTVCT 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.

Survival outcome by early chemoradiation therapy salvage or early surgical salvage for the treatment of hypopharyngeal cancer

Objective To compare survival data between patients who had surgery followed by concomitant chemoradiation therapy (CCRT) versus CCRT followed by early surgical salvage. Study Design Retrospective study. Methods We retrospectively analyzed 202 patients with hypopharyngeal carcinoma (HPC) who were treated with different treatment strategy according to the choice of the patients by surgery first or CCRT first. In 72 (35.6%) cases, the primary treatment was surgery. Postoperative radiation therapy was given to 47 patients. Radiation therapy was the primary treatment in 130 (64.4%) patients; among them, 69 (34.2%) patients received salvage surgery within 2 months after CCRT course if there was a residual tumor visible on post-CCRT CT image or clinically residual tumor. Results and Conclusion The 5-year disease-specific survival rate was 80% for stage I-II, 44.8% for stage III, and 14.3% for stage IV disease. Surgery plus concomitant chemoradiotherapy led to a better survival rate than CCRT plus salvage surgery in patients with stage III-IV HPC.

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

The study aimed to investigate the prognostic effects of interim 18fluoro‐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.

Low-dose, prophylactic, extended-field, intensity-modulated radiotherapy plus concurrent weekly cisplatin for patients with stage IB2-IIIB cervical cancer, positive pelvic lymph nodes, and negative para-aortic lymph nodes.

Objective The objective of this study was to assess prospectively the clinical outcomes of low-dose prophylactic extended-field, intensity-modulated radiotherapy (IMRT) plus concurrent weekly cisplatin for patients with stage IB2-IIIB cervical cancer, positive pelvic lymph nodes (PLNs), and negative para-aortic lymph nodes (PALNs). Methods Thirty-two patients with stage IB2-IIIB cervical cancer with positive PLN and negative PALN were included prospectively. All lymph nodes were assessed with positron emission tomography. The PALN field, including lymphatics from the superior border of L1 to the L4-L5 interphase, was irradiated concurrently with pelvic IMRT with a prescribed dose of 40 Gy in 25 fractions. Chemotherapy consisted of cisplatin delivered weekly at a dose of 40 mg/m2. Using historical controls treated with pelvic radiotherapy, the survival curves were compared to assess the difference between the 2 treatment periods. Results Thirty-one patients completed the allocated extended-field IMRT, and all finished the planned pelvic IMRT and brachytherapy. Acute ≥ grade 3 gastrointestinal, genitourinary, and hematologic toxicities were seen in 2, 1, and 18 patients, respectively. During a median follow-up of 33 months, 5 patients developed out-field distant recurrences. One patient had a late grade 3 gastrointestinal complication, and 1 patient had genitourinary toxicity. The 3-year actuarial overall survival, disease-free survival, and distant metastasis–free survival for the study cohort and historic controls were 87% versus 62% (P = 0.02), 82% versus 54% (P = 0.02), and 79% versus 57% (P = 0.01), respectively. Conclusions Extended-field IMRT of 40 Gy to the PALN plus concurrent cisplatin can effectively eradicate subclinical disease at the PALN and improve the outcome for patients with PLN-positive stage IB2-IIIB cervical cancer.

Clinical implications of elevated pretreatment carcinoembryonic antigen in patients with advanced squamous cell carcinoma of the uterine cervix.

Object: The aim of this study was to investigate the prognostic significance of pretreatment levels of carcinoembryonic antigen (CEA) for treatment outcome in comparison with squamous cell carcinoma antigen (SCC) in cervical cancer patients following concurrent chemoradiotherapy (CCRT). Methods: A total of 148 patients with stage IB2–IVA squamous cell carcinoma of the uterine cervix who were treated with a full course of CCRT were included for analysis. The pretreatment blood samples of tumor markers were obtained before initiation of CCRT. Values for SCC <2 and CEA <5 ng/ml, respectively, were regarded as normal. Cox’s proportional hazards model was performed for risk stratification for disease-free survival (DFS) and cause-specific survival (CSS). Results: Pretreatment CEA and SCC levels were elevated in 37.2 and 64.2% of the patients, respectively. Positive pelvic lymph node, stage and pretreatment CEA levels >10 ng/ml were three independent prognostic factors for DFS and CSS. The 5-year DFS for the low- and high-CEA groups was 80 and 56%, respectively (p = 0.02, hazard ratio 2.6), whereas the 5-year CSS for the low- and high-CEA groups was 84 and 63%, respectively (p = 0.01, hazard ratio 3.2). Conclusion: Despite lower sensitivity, pretreatment CEA levels >10 ng/ml predict a poor outcome in advanced squamous cell carcinoma of the cervix.