Shih Neng Yang

The adverse effect of treatment prolongation in cervical cancer byhigh-dose-rate intracavitary brachytherapy

BACKGROUND AND PURPOSE The potential risk of prolongation of treatment time in cervical cancer has been reported for many low-dose rate (LDR) studies, with an estimated loss of local control ranging from 0.3 to 1.6% per day of treatment prolongation. Since the treatment schedule for fractionated high-dose rate intracavitary brachytherapy (HDRICB) is not directly comparable with that for low-dose rate studies, this report aims to evaluate the adverse effect of treatment prolongation specifically for cervical cancer treated with HDRICB. MATERIAL AND METHODS From September 1992 to December 1997, 257 patients diagnosed with uterine cervical cancer (35 Ib, 26 IIa, 122 IIb, 10 IIIa, 57 IIIb, 7 IVa), who underwent external radiotherapy combined with between two and four courses of HDRICB and a minimum of 3 years of follow-up (median 57 months), were analyzed. Treatment consisted of irradiation of the whole pelvis with 44-45 Gy consisting of 22-25 fractions by 5 weeks, with the dose boosted to 54-58 Gy (with central shielding) for patients diagnosed as FIGO stage IIb-IVa bilateral parametrial disease. HDRICB was performed using an Ir-192 remote afterloading technique at 1-week intervals. The standard prescribed dose for each course of HDRICB was 7.2 Gy to point A for three insertions (before July 1995), or 6.0 Gy to point A for four insertions (after July 1995). Total prescribed point A doses (external beam radiotherapy+HDRICB) ranged from 58 to 71.6 Gy (median, 65.6 Gy) for stage IB-IIA, while analogous dosage for larger lesions (stage IIb-IVa) ranged from 59 to 75.6 Gy (median, 65.6 Gy). Kaplan-Meier and multivariate analyses were used to test the effect of treatment time on pelvic control rate (PCR) and cause-specific survival (CSS) at 5 years. RESULTS Median treatment time was 63 days. For all stages of disease, the 5-year CSS and PCR were significantly different comparing treatment times of less than and greater than or equal to 63 days [83% and 65% (P=0.004], 93% and 83% (P=0.02), respectively]. These associations were also significant for stage Ib/IIa [97% and 79% (P=0.01), and 100% and 87% (P=0.02), respectively), but not for stage IIb [75% and 72% (P=0.79), and 93% and 87% (P=0.83), respectively] or stage III [66% and 49% (P=0.2), and 83% and 72% (P=0.21), respectively]. Multivariate analysis identified three prognostic factors for CSS, stage (P<0.001), tumor response to external RT (P=0.001), and overall treatment time (OTT; P=0.006). Prognostic factors for pelvic failure were stage (P<0.001), tumor response to external RT (P=0.001), and OTT (P=0.03). Prolongation of treatment time resulted in a daily decrease in pelvic control rate of 0.67% overall, and 0.43% for stage Ib-IIa, 0.57% for stage IIb, and 0.73% for stage III patients. CONCLUSION Analysis of the data from the current study demonstrates that the adverse effect of treatment prolongation was observed later in the treatment course for the high-dose rate (HDR) series compared to the LDR analog, however, treatment-time prolongation still negatively influenced the cause-specific survival and pelvic control rate for both dosage groups.

The prediction of late rectal complications following the treatment of uterine cervical cancer by high-dose-rate brachytherapy

PURPOSE This study aimed to correlate patient, treatment, and dosimetric factors with the risk of late rectal sequelae in patients with uterine cervical cancer treated with external beam radiation therapy (EBRT) and high dose rate intracavitary brachytherapy (HDRICB). METHODS AND MATERIALS From September 1992 to December 1995, a total of 128 patients with uterine cervical cancer, who were treated and survived more than 12 months, were evaluated. After EBRT with 40-44 Gy/20-22 Fr/4-5 weeks to the whole pelvis, the dose was boosted up to 54-58 Gy with central shielding for patients with bilateral parametria of Stage IIb or greater. HDRICB consisted of three to four insertions at doses of 5-7.2 Gy (to Point A) at intervals of 1 week. Patient and treatment factors were analyzed using logistic regression analysis and the cumulative rectal biologic equivalent dose (CRBED) was calculated. RESULTS After 30-75 months of follow-up (median, 43 months), 38 patients (29.7%) had late rectal sequelae. Patients who had Stage IIb-IVa disease, cumulative rectal dose (external RT + total ICRU rectal dose) greeater than 65 Gy, or age greater than 70 years had a high risk of developing late rectal sequelae. When 110 Gy was used as the cut-off value, 19.6% (10 of 51) of patients whose CRBED was less than 110 Gy had rectal complications, while 36.4% (28/77) of patients whose CRBED was greater than 110 Gy developed rectal complications. CONCLUSION Risk factors of late rectal complications were advanced stage, age greater than 70 years, and cumulative rectal dose of greater than 65 Gy.

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.

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.