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.

Lack of the dose-rate effect of 192Ir source activity on pelvic control and late complications after high-dose-rate brachytherapy for cervical cancer.

This study aimed to assess the dose-rate effect of (192)Ir source activity on pelvic control and late complications following high-dose-rate intracavitary brachytherapy (HDRICB) for cervical cancer patients. Two hundred and twelve patients were enrolled in this study. They were treated with external beam radiotherapy to the pelvis, after which HDRICB was performed using (192)Ir remote after-loading at 1-week intervals for 4 or 5 sessions. Source activity was defined as the average of source activity in each HDRICB session. Dose-rate effect was analyzed after stratification of stage and biologically effective dose (BED). The 5-year pelvic relapse-free survival was 88% for all patients. Forty-two patients developed late rectal complications (13 grade 1, 23 grade 2, 6 grade 3-4). Twenty-seven patients had grade 2 and higher late bladder complications (14 grade 2, 13 grade 3-4). There was no dose-rate effect on pelvic control or complications when source activity was stratified. Multivariate analysis demonstrated a high risk of grade 2 and higher rectal sequelae in patients whose rectal BED >or= 110 Gy(3) (p = 0.039, hazard ratio 2.05). The high risk factors for grade 2 and higher bladder complications were a bladder BED >or= 100 Gy(3) (p = 0.03, hazard ratio 4.37). This study demonstrated no dose-rate effect of (192)Ir source in HDRICB for cervical cancer in terms of pelvic control or radiation injuries. Careful monitoring of the BED values for rectum and bladder is a scrutinizing factor for minimizing late sequelae.

Geometrical sparing factors for the rectum and bladder in the prediction of grade 2 and higher complications after high-dose-rate brachytherapy for cervical cancer.

PURPOSE: This study aimed to assess the predictive values of geometrical sparing factors for the rectum and bladder in high-dose-rate intracavitary brachytherapy (HDRICB) for Grade 2 and higher late sequelae in patients with cervical cancer. METHODS: A total of 392 patients were enrolled in this study. They were treated with external beam radiotherapy to the pelvis, after which HDRICB was performed using Ir-192 remote after-loading at 1-week intervals for three or four sessions. The geometrical sparing factor (GSF) was defined as the average of the ratios between the reference doses and the Point A dose. RESULTS: A total of 46 patients (11.7%) had Grade 2 or higher late rectal complications (36 Grade 2, 9 Grade 3, and 1 Grade 4). In all, 32 patients (8.2%) had Grade 2 or higher late bladder complications (14 Grade 2, 16 Grade 3, and 2 Grade 4). Multivariate analysis demonstrated a high risk of rectal sequelae in patients who developed bladder complications (p = 0.0004, hazard ratio 3.54) and had a rectal GSF greater than 0.7 (p = 0.01, hazard ratio 1.99). The high risk factors for bladder complications were development of rectal complications (p = 0.0004, hazard ratio 3.74), concurrent chemotherapy (p = 0.0001, relative risk 3.94), and a bladder GSF greater than 0.9 (p = 0.01, hazard ratio, 2.53). CONCLUSION: This study demonstrates the predictive value of GSFs in HDRICB for cervical cancer. Patients with rectal GSFs greater than 0.7 or bladder GSFs greater than 0.9 are at risk for Grade 2 and higher late sequelae.

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

BACKGROUND: To investigate the prognostic value of volumetric analysis in patients with stage III-IVA hypopharyngeal cancer treated with concurrent chemoradiotherapy (CCRT). METHODS: Seventy-six stage III-IVA hypopharyngeal cancer patients without bulky lymph nodes were enrolled for a volumetric analysis. The pyriform sinus was the principal site of involvement in the 63 cases. All patients were allocated a course of CCRT. Tumor volume measurement was derived using separate calculations for the primary tumor volume (pGTV) and the nodal tumor volume (nGTV). RESULTS: The pGTV ranged from 3.8 to 152.4 mL (mean, 33.4 mL). The 3-year cause-specific survival (CSS) was 75% for those with a pGTV <30 mL and 20% when the pGTV was >or=30 mL (p = .0001). Furthermore, the 3-year primary tumor relapse-free survival (PRFS) was 72% for those with a pGTV <30 mL and 23% when the pGTV were >or=30 mL (p = .0001). The 3-year PRFSs for <30 mL and >or=30 mL were 74% and 25% for stage III disease (p = .01) and 65% and 22% for stage IVA tumors (p = .01), respectively. Multivariate analyses of the CSS revealed a single prognostic factor, namely pGTV <30 mL versus >or=30 mL (p = .0001, hazard ratio 2.84). Multivariate analyses of the PRFS gave a similar finding, with a pGTV >or=30 mL (p = .0001, hazard ratio 2.55) being significant. CONCLUSION: A patient's pGTV is a strong outcome predictor for hypopharyngeal cancer treatment using CCRT. Therefore, a selected group of patients, mainly those with tumor volumes <30 mL should be considered for laryngeal preservation.

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.

Risk stratification for failure in patients with advanced cervical cancer after concurrent chemoradiotherapy: another way to optimise treatment results.

AIMS: To identify risk factors for disease-free survival (DFS) and para-aortic lymph node (PALN) metastasis in advanced cervical cancer patients after concurrent chemoradiotherapy (CCRT) using risk stratification. MATERIALS AND METHODS: In total, 148 patients with stage IB2-IVA cervical cancer without PALN metastasis treated with a full course of CCRT were included for analysis. Radiotherapy consisted of external beam irradiation followed by four courses of high-dose rate intracavitary brachytherapy using 6.0 Gy to point A. Chemotherapy consisted of weekly cisplatin at a dose of 40mg/m(2) for a planned six cycles. Cox's proportional hazards model was used for risk stratification for DFS and PALN relapse-free survival. RESULTS: Patients were divided into low- and high-risk groups. The low-risk group was composed of patients with stage IB-IIB disease without enlarged pelvic nodes, whereas the high-risk group was comprised of patients with stage IB2-IIB tumours with enlarged nodes or those with stage III-IVA disease. The 4-year DFS for the low- and high-risk groups was 83 and 52%, respectively (P=0.0001, relative risk 4.51, 95% confidence interval 1.3-10.7), whereas the 4-year PALN metastasis-free survival for the low- and high-risk groups was 92 and 61%, respectively (P=0.0003, relative risk 4.93, 95% confidence interval 1.2-12.5). CONCLUSION: The risk of failure in advanced cervical cancer patients treated in the CCRT era can be predicted. For patients with high risk of PALN relapse, this study can provide patient selection criteria when considering prophylactic PALN irradiation.

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). METHODS: From January 2000 through February 2004, 63 patients with HPC were enrolled for a retrospective analysis. The pyriform sinus was the principle site of involvement in 62 cases. All patients received with 1.8 Gy daily to a total dose of 68.4 to 73.8 Gy (median, 70.2 Gy). Contrast-enhanced CT images were transferred to a planning system. Tumor volume measurement was derived from summation of the primary and metastatic nodal tumor. RESULTS: With a median follow-up of 38 (range, 24-68) months, the 5 year local relapse-free survival (LRFS) was 83% for patients with T1 to T2 disease, 46% for those with T3 disease, and 40% for those with T4 disease (P = .01). The 5 year LRFS was 75% for those with tumors less than 40 mL and 26% when volumes were 40 mL of larger (P = .0001). For patients with T3 to T4 disease, the 5 year LRFS was 70% for those with tumors less than 40 mL and 24% when volumes were 40 mL or larger (P = .0005). Multivariate analyses of local relapse-free survival revealed two prognostic factors: tumor volume more than 40 mL and the involvement of the larynx. CONCLUSIONS: CT-based tumor volumes are a strong predictor of outcomes for HPC treated using definitive RT. A selected group of patients, mainly those with tumor volumes less than 40 mL, should be considered for laryngeal preservation.

Concurrent weekly cisplatin plus external beam radiotherapy and high-dose rate brachytherapy for advanced cervical cancer: a control cohort comparison with radiation alone on treatment outcome and complications.

PURPOSE: To test, though a control-cohort study, the hypothesis that concurrent chemoradiotherapy (CCRT) using weekly cisplatin, plus high-dose rate intracavitary brachytherapy (HDRICB) is superior to radiation (RT) alone in patients with advanced cervical cancer. METHODS AND MATERIALS: A total of 171 patients with Stage IIB-III cervical cancer were enrolled in this study. Seventy patients were treated with CCRT and the results were compared with those of 101 patients who had been treated with RT using the same protocol at an early period. RT consisted of 45 Gy in 25 fractions to the whole pelvis, followed by a 12.6-Gy boost to the parametrium. Four courses of HDRICB using 6.0 Gy to Point A were performed. Chemotherapy consisted of weekly cisplatin at a dose of 40 mg/m(2) for 5-6 cycles. RESULTS: The 4-year actuarial survival was 74% for the CCRT group and 68% for the RT group (p = 0.60). The 4-year pelvic relapse-free survival was 87% for the CCRT group and 85% for the RT group (p = 0.37). The 4-year distant metastases-free survival was 75% for the CCRT group and 76% for the RT group (p = 0.44). The cumulative incidence of gastrointestinal and genitourinary injuries of grade 3 or above was 14.3% for the CCRT group and 7.9% for the RT group (p = 0.19). CONCLUSION: This study did not show a survival benefit of CCRT with weekly cisplatin and HDRICB for Stage II-III cervical cancer, nor did it demonstrate a significant increase of late complications when comparing with RT alone.

Comparative dosimetric study of two strategies of intensity-modulated radiotherapy in nasopharyngeal cancer.

This study compared the target volume coverage and normal tissues sparing of simultaneous integrated boost (SIB-IMRT, 1-phase) and sequential-IMRT (2-phase) for nasopharyngeal carcinoma (NPC). Fourteen consecutive patients with newly diagnosed primary NPC were enrolled in this study. The CT images were transferred to a commercial planning system for structural delineation. The gross tumor volume (GTV) included gross nasopharyngeal tumor and involved lymph nodes of more than 1-cm diameter. The clinical target volume (CTV) modeled two regions considered to represent different risks. CTV1 encompassed the GTV with 5-10-mm margin of adjacent tissues. CTV2 encompassed ipsilateral or contralateral elective nodal regions at risk of harboring microscopic tumor. A commercial IMRT treatment planning system (Eclipse Version 7.1) was used to provide treatment planning. Seven fixed-gantry (0 degrees, 50 degrees, 100 degrees, 150 degrees, 210 degrees, 260 degrees, 310 degrees ) angles were designated. The 14 patients were treated with sequential-IMRT, and treatment was then replanned with an SIB strategy to compare the dosimetric difference. For the sequential strategy, the dose delivered to CTV1/CTV2 in the first course was 54 Gy (1.8 Gyx30 Fr); while CTV1 was boosted by an additional 16.2 Gy (1.8 Gyx9 Fr) in the second course. For SIB-IMRT, the dose prescribed to CTV1 was 69.7 Gy (2.05 Gyx34 Fr); 56.1 Gy was given to CTV2 (1.65 Gyx34 Fr). A statistical analysis of the dose-volume-histogram of target volumes and critical organs was performed. Paired Student's t-test was used to compare the dosimetric differences between the two techniques. The mean dose to CTV1 was 101.7+/-2.4% and 102.3+/-3.1% of the prescribed dose for SIB-IMRT and sequential-IMRT, respectively. The mean CTV2 dose was 109.8+/-4.7% of the prescribed dose for SIB-IMRT and 112.6+/-6.0% of the prescribed dose for sequential-IMRT. The maximal dose to the spinal cord was 4489+/-495 cGy and 3547+/-767 cGy for SIB and sequential-IMRT (p=0.0001), respectively. The maximal dose to brain stem was significantly higher using SIB technique (5284+/-551 cGy) than sequential-IMRT (4834+/-388 cGy) (p=0.0001). The mean dose to the parotid gland and ear apparatus was significantly lower using SIB-IMRT. The mean dose to the right/left parotids was 2865+/-320 cGy/2903+/-429 cGy and 3567+/-534 cGy/3476+/-489 cGy for SIB and sequential-IMRT, respectively (p=0.0001). Target coverage was the same for both techniques; the dose distribution in the elective nodal area with SIB was superior to that with sequential-IMRT. SIB-IMRT provides better sparing of parotid gland and inner ear structures. Extra caution should be taken when applying SIB-IMRT since critical organs close to the boost volume may receive higher doses.

Radiation injury to intestine following hysterectomy and adjuvant radiotherapy for cervical cancer.

OBJECTIVE: To evaluate the risk factors for nonrectal radiation-induced intestinal injury (NRRIII) following adjuvant radiotherapy (RT) for cervical cancer using a retrospective review of medical records. METHODS: From September 1992 to December 1998, 164 patients with uterine cervical cancer that had completed their allocated adjuvant radiotherapy at the Chinese Medical University Hospital were enrolled for NRRIII analysis. The patients were classified into two groups according to the extent of surgery. Group A consisted of 110 patients (International Federation of Gynecology and Obstetrics [FIGO] stage: IB, n = 87; IIA, n = 21; IIB, n = 2) undergoing radical hysterectomy and bilateral pelvic lymph node dissection, while Group B was composed of 54 analogs receiving adjuvant radiotherapy following incident extrafascial hysterectomy. Treatment consisted of external beam radiotherapy (EBRT) and high-dose-rate intravaginal brachytherapy (HDRIVB). Initially, the whole pelvis was treated with 10 MV X-rays. After irradiation (44 Gy in 22 fractions over 4-5 weeks), the field was limited to the true pelvis and a further 10-20 Gy delivered in 5-10 fractions. For 21 patients in group A without pelvic lymph node metastasis or lymphovascular invasion, the radiation field was confined to the lower pelvis, with a prescribed dose of 50-58 Gy delivered over 5-6 weeks. HDRIVB was performed using an Ir-192 remote after-loading technique at 1-week intervals. A total of 159 patients (97%) received two insertions, while 5 had only one. The standard prescribed HDRIVB dose was 7.5 Gy to the vaginal surface. Logistic regression analysis was performed for assessment of the factors associated with NRRIII. RESULTS: After 38-119 months of follow-up (median, 60), 22 patients (13.4%) developed Radiation Therapy Oncology Group (RTOG) grade 2 or greater NRRIII at a median latency of 18 months (range, 5-48). Four patients were diagnosed as grade 3 complications requiring surgery and three had expired. The independent factors for NRRIII were radical hysterectomy (P = 0.04, relative risk 2.45), lower-pelvic dose >54 Gy (P = 0.0001, relative risk 10.27), and age over 60 years (P = 0.001, relative risk 5.45). The incidence of NRRIII for patients receiving whole and lower-pelvic irradiation was 14.5% and 10.6%, respectively (P = 0.45). Although there was no statistical significance comparing the two external beam irradiation strategies in terms of NRRIII, all four patients with grade 3 NRRIII underwent whole pelvic irradiation. CONCLUSION: This study identifies three predictive factors for the development of NRRIII following adjuvant radiotherapy for cervical cancer. Limiting the EBRT dose to less than 54 Gy, meticulous patient selection in the elderly, careful planning of the irradiated field, and the constraint of vaginal brachytherapy are four approaches to optimization of postoperative adjuvant radiotherapy.

Comparative study of reference points by dosimetric analyses for late complications after uniform external radiotherapy and high-dose-rate brachytherapy for cervical cancer.

PURPOSE: This study aimed to correlate and compare the predictive values of rectal and bladder reference doses of uniform external beam radiotherapy without shielding and high-dose-rate intracavitary brachytherapy (HDRICB) with late sequelae in patients with uterine cervical cancer. METHODS AND MATERIALS: Between September 1992 and December 1998, 154 patients who survived more than 12 months after treatment were studied. Initially, they were treated with 10-MV X-rays (44 to 45 Gy/22 to 25 fractions over 4 to 5 weeks) to the whole pelvis, after which HDRICB was performed using (192)Ir remote afterloading at 1-week intervals for 4 weeks. The standard prescribed dose for each HDRICB was 6.0 Gy to point A. Patient- and treatment-related-factors were evaluated for late rectal complications using logistic regression modeling. RESULTS: The probability of rectal complications showed better correlation of dose-response with increasing total ICRU (International Committee on Radiotherapy Units and Measurements) rectal dose. Multivariate logistic regression demonstrated a high risk of late rectal sequelae in patients who developed rectal complications (p = 0.0001;relative risk, 15.06;95% CI, 2.89 approximately 43.7) and total ICRU rectal dose greater than 16 Gy (p = 0.02;relative risk, 2.07;95% CI, 1.13 approximately 4.55). The high risk factors for bladder complications were seen in patients who developed rectal complications (p = 0.0001;relative risk, 15.2;95% CI, 2.81 approximately 44.9) and total ICRU bladder dose greater than 24 Gy (p = 0.02;relative risk, 8.93;95% CI, 1.79 approximately 33.1). CONCLUSION: This study demonstrated the predictive value of ICRU rectal and bladder reference dosing in HDRICB for patients receiving uniform external beam radiation therapy without central shielding. Patients who had a total ICRU rectal dose greater than 16 Gy, or a total ICRU bladder dose over 24 Gy, were at risk of late sequelae.

Postoperative radiotherapy for patients with invasive cervical cancer following treatment with simple hysterectomy.

BACKGROUND: This study aimed to investigate the survival and complications of patients who received adjuvant radiotherapy for invasive cervical cancer following inadvertent simple hysterectomy. METHODS: From September 1992 through to December 1998, 54 patients who had received simple hysterectomies for benign lesions, but were incidentally found with invasive carcinoma of the cervix in the surgical specimen, were referred to our department for postoperative irradiation. They were categorized into two groups according to pathological findings. Group A consisted of 25 patients whose specimen showed microinvasion alone, with the depth of stromal invasion <5 mm. Group B consisted of 29 patients whose pathological findings included deep stromal invasion, tumor emboli in cervix, lymphovascular permeation, positive or close resection margin, endometrial or myometrial invasion and vaginal involvement. After external beam irradiation dose of 44 Gy in 22 fractions over 4-5 weeks to the whole pelvis, the radiation field was reduced to true pelvis for a further 10 Gy in five fractions. Brachytherapy was performed using an Ir-192 remote after-loading technique for 1-2 courses. The prescribed dose for each treatment was 7.5 Gy to the vaginal surface. A retrospective analysis was conducted to compare radiation-therapy outcomes for these 54 patients. RESULTS: After 37-102 months of follow-up (median, 58 months), 47 patients were alive without evidence of disease; five patients in Group B died of the disease (three with distant metastasis, one with local relapse, one with both). Two patients died of other concurrent diseases. The 5-year actuarial survival (AS) and disease-free survival (DFS) rates for all patients were 88 and 90%, respectively. The respective 5-year AS and DFS rates for Group A/B were 95/82% (P = 0.07) and 100/83% (P = 0.03). Ten patients (18.5%) developed RTOG Grade 1-4 rectal complications. Five patients (9.3%) developed RTOG Grade 3-4 bladder complications. Eight patients (14.8%) had RTOG Grade 1-4 non-rectal gastrointestinal complications. CONCLUSIONS: For patients with invasive cervical cancer following inadvertent simple hysterectomy, external beam radiotherapy combined with one or two fractions of intravaginal brachytherapy could achieve satisfactory disease control. It is recommended to select a high-risk group for intensive adjuvant treatment. Further optimization of the irradiation strategy is also imperative to decrease the incidence of complications.

High dose-rate brachytherapy for elderly patients with uterine cervical cancer.

BACKGROUND: The need for radiotherapy (RT) in cancer treatment for the elderly patient is growing. The purpose of this study was to analyze the efficacy and complication rate for radiotherapy, using external-beam irradiation (EBRT) and high dose-rate intracavitary brachytherapy (HDRICB), for patients aged 70 years or older with carcinoma of the uterine cervix. METHODS: From September 1992 to December 1997, 295 patients diagnosed with uterine cervical cancer completed RT at the Shin Kong Memorial Hospital and China Medical College Hospital. Two hundred and fifty-eight patients [International Federation of Gynecology and Obstetrics (FIGO) stage distribution: 35 Ib, 26 IIa, 122 IIb, 10 IIIa, 58 IIIb, 7 IVa] who had undergone at least two courses of HDRICB and a minimum of 3 years of follow-up, were evaluated. A retrospective analysis was conducted to compare the outcome of radiation therapy for the 179 patients under 70 years of age (younger group) and the 79 patients aged 70 years or older (older group). The RT consisted of EBRT followed by HDRICB. After a total EBRT dose of 40-45 Gy/20 in 25 fractions, irradiating the whole pelvis over 4-5 weeks, dosage for patients diagnosed as FIGO stage IIb-IVa bilateral parametrial disease was boosted to 54-58 Gy, with central shielding. HDRICB was administered at 1-week intervals using an Ir-192 remote after-loading technique. Ninety-nine patients (38.4%) received three fractions of HDRICB, while 156 patients (60.5%) had four fractions. Total prescribed Point A dosages (EBRT + HDRICB) ranged from 58 to 71.6 Gy (median, 65.6 Gy) for stage IB-IIA, while for larger lesions (stage IIB-IVA) analogous dosages were 59-75.6 Gy (median, 65.6 Gy). Median follow-up durations for the older and younger groups were 56/55 months, respectively. RESULTS: The respective 5-year actuarial survivals (AS) for the older and younger groups were 82/85% for stage Ib, 65/65% for IIa, 61/71% for IIb and 35/59% for IIIa-b. The 5-year cause-specific survivals (CSS) for the older and younger groups were 100/95% for stage Ib, 85/75% for IIa, 78/72% for IIb and 42/61% for IIIa-b. The 5-year pelvic relapse-free survivals (PRFS) for the older and younger groups were 100/100% for stage Ib, 91/93% for IIa, 91/90% for IIb and 67/80% for IIIa-b. The 5-year distant metastasis-free survivals (DMFS) for older and younger groups were 100/100% for stage Ib, 92/88% for IIa, 84/73% for IIb and 55/75% for IIIa-b. There was no statistically significant survival difference on comparing the two groups according to stage. The gross tumor-free ratios after EBRT (NRT) for the older and younger groups were 44.3/24.5% (P = 0.001). The 5-year CSS for the 35 NRT patients was 88% for the older group, while for the 44 patients diagnosed with gross residual tumor after EBRT (GRT) it was 64% (P = 0.001). Twelve (15.0%) of the 79 older patients and 14 (7.8%) of the 179 younger patients developed RTOG grade 3-4 rectal complications (P = 0.12), while seven (8.9%) of the 79 older patients and 10 (5.6%) of the 179 younger patients developed RTOG grade 3-4 small bowel complications (P = 0.34). CONCLUSION: Radiation therapy, consisting of a combination of EBRT and three or four fractions of HDRICB, proved to be effective for older patients. Further optimization of treatment policy is essential by changing the HDRICB fractionation strategy, shortening the treatment time and designing combination drug regimens that are both effective and tolerable during radiotherapy.

The adverse effect of treatment prolongation in cervical cancer by high-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.

Prediction of chemotherapy response in untreated malignant lymphomas using technetium-99m methoxyisobutylisonitrile scan: comparison with P-glycoprotein expression and other prognostic factors. A preliminary peport.

BACKGROUND: The purpose of this study was to predict chemotherapy response in untreated malignant lymphomas using technetium-99m methoxyisobutylisonitrile (Tc-MIBI) scan. METHODS: Twenty-five patients with malignant lymphoma were studied before receiving chemotherapy. Early Tc-MIBI scan was performed 10 min after intravenous injection of Tc-MIBI. Immunohistochemical analyses were performed on multiple non-consecutive sections of the biopsy specimens to determine Pgp expression. Chemotherapy response was evaluated in the first 1-2 years after completion of treatment by clinical and radiological methods. RESULTS: The mean tumor-to-background ratio of the 15 patients with good response (3.3 +/- 0.6) was significantly higher than that of the 10 patients with poor response (1.2 +/- 0.1). Among the 15 patients with good response to chemotherapy, all had positive Tc-MIBI scan results but negative Pgp expression. Among the 10 patients who had poor response to chemotherapy, all 10 had negative Tc-MIBI scan, but six patients had positive Pgp expression and four had negative Pgp expression. Significant differences were found in the incidences of good and poor responses determined by Tc-MIBI scan and Pgp expression. However, there were no significant differences in the incidences of good and poor responses for other prognostic factors. CONCLUSION: Compared with other prognostic factors, early Tc-MIBI scan more accurately predicts chemotherapy response in patients with malignant lymphoma.

Using technetium-99m-tetrofosmin scan to predict chemotherapy response of malignant lymphomas, compared with P-glycoprotein and multidrug resistance related protein expression.

The ability of technetium-99m tetrofosmin (Tc-TF) scan to predict chemotherapy response in malignant lymphomas (ML) was compared with the predictive ability of P-glycoprotein (Pgp) and multidrug resistance related protein (MRP) expression. Before chemotherapy, 25 ML patients were enrolled in this study. Scans were performed 10 min after intravenous injection of Tc-TF. Immunohistochemical analyses were performed on ML specimen sections to evaluate Pgp and MRP expression. Chemotherapy response was evaluated in the first 1-2 years after completion of chemotherapy. Based on Tc-TF scan results, the mean tumor-to-background (T/B) ratio of the 15 patients with good response (3.23 +/- 0.56) was significantly higher than that of the 10 patients with poor response (1.18 +/- 0.11). All 15 patients with good response had positive Tc-TF scan results but negative Pgp and MRP expression. All 10 patients with poor response had negative Tc-TF scan results but positive Pgp or MRP expression. No significant differences in the incidences of good and poor response results were found for patients with Hodgkin's disease versus non-Hodgkin's lymphoma, with stage I-II versus stage III-IV, with age > 40 versus age < or = 40 years, or with B symptoms versus without B symptoms. Tc-TF scan results, which may represent either Pgp or MRP expression, accurately predict chemotherapy response in patients with ML.