Long-term results of high-dose-rate brachytherapy in the primary treatment of medically inoperable stage I-II endometrial carcinoma

PURPOSE: Total-abdominal hysterectomy and bilateral salpingo-oophorectomy (TAHBSO) is the gold-standard therapy for patients with endometrial carcinoma. However, patients with high operative risks are usually treated with radiation therapy (RT) alone. The goal of this study was to update our experience of high-dose-rate brachytherapy (HDRB), with or without external-beam irradiation (EBRT), for such patients. METHODS AND MATERIALS: Between 1984 and 2003, 38 patients with Stage I and Stage II adenocarcinoma of the endometrium considered high operative risk received RT as the primary treatment. The median age was 74.1 years. Before 1996, the local extent of the disease was assessed by an examination under anesthesia (EUA) and by EUA and magnetic resonance imaging (MRI) thereafter. Eight patients (21%) were treated with combined HDRB and EBRT, and 30 patients (79%) were treated with with HDRB alone. The median HDRB dose was 23.9 Gy, typically delivered in 3 fractions in a weekly schedule. The median EBRT dose was 42 Gy. RESULTS: At a median follow-up of 57.5 months for patients at risk, 11 patients (29%) have failed: 6 patients (16%) locally, 4 patients (10.5%) distantly, and 1 patient (3%) locally and distantly. Local failure was established by biopsy, and 4 patients were salvaged by TAHBSO. Higher stage and higher grade were both associated with increased failure rate. The 15-year disease-specific survival (DSS) was 78% for all stages, 90% for Stage I, and 42% for Stage II (p < 0.0001). The 15-year DSS was 91% for Grade I and 67% for Grade II and III combined (p = 0.0254). Patients with Stage I disease established by MRI (11 patients) and who received a total HDRB dose of 30 Gy had a DSS rate of 100% at 10 years. Four patients experienced late toxicities: 1 Grade II and 3 Grade III or IV. CONCLUSION: Medically inoperable Stage I endometrial carcinoma may be safely and effectively treated with HDRB as the primary therapy. In selected Stage I patients, our results are equivalent to that of surgery. We believe that the alternative option of HDRB as the primary therapy for selected Stage I endometrial carcinoma, even in patients with low operative risks, needs further evaluation.     

Definitive radiotherapy for patients with isolated vaginal recurrence of endometrial carcinoma after hysterectomy

PURPOSE: To determine the outcome of patients after radical radiotherapy (RT) for isolated vaginal recurrence of endometrial carcinoma and to determine the clinical and pathologic predictors of outcome. METHODS AND MATERIALS: We reviewed the records of 91 patients treated at our institution between 1960 and 1997 with radical RT for vaginal recurrence after definitive surgery for endometrial carcinoma. Thirty-one percent of the patients received external beam RT (EBRT) alone, 12% received brachytherapy alone, and 57% received a combination. The median dose of radiation was 75 Gy (range 34-122). All end points were measured from the time of the first recurrence. The median duration of follow-up after recurrence was 58 months (range 1-289). RESULTS: The 2- and 5-year local control (LC) rate and overall survival rate was 82% and 75% and 69% and 43%, respectively. The median time from initial diagnosis of endometrial cancer to death from disease was 38 months. On univariate analysis, a dose to the relapse site of > or =80 Gy and EBRT plus brachytherapy vs. single-modality therapy were significant predictors of improved LC. On multivariate analysis, only the type of treatment correlated significantly with LC (p = 0.03). On univariate analysis, Grade 1 or 2 vs. Grade 3 tumor and EBRT plus brachytherapy vs. single-modality therapy were significant predictors of improved overall survival. CONCLUSION: RT provides excellent LC of isolated vaginal recurrences of endometrial carcinoma, particularly when high doses are given using a combination of EBRT and brachytherapy. However, distant metastases frequently develop despite local disease control, contributing to a 5-year overall survival rate of <50%. For patients who have an isolated vaginal recurrence, the time from initial diagnosis of endometrial cancer to death from disease is usually >3 years. For this reason, in studies of adjuvant RT, long-term follow-up is required to permit evaluation of the impact of treatment on survival.     

Definitive radiotherapy in the management of isolated vaginal recurrences of endometrial cancer

PURPOSE: The aim of our study was to assess prognostic factors and overall survival after salvage radiotherapy for patients who had endometrial carcinoma and who experienced an isolated vaginal recurrence. METHODS AND MATERIALS: We reviewed the records of 50 patients treated at our institution between 1967 and 2003 for an isolated vaginal recurrence of endometrial carcinoma. Initial treatment for endometrial carcinoma was definitive surgery in 49 patients and definitive radiotherapy in 1 patient. The median time from initial diagnosis of endometrial carcinoma to recurrence was 25 months (range, 4-179 months). Three patients (6%) received external-beam radiotherapy alone, 8 patients (16%) received brachytherapy only, and 39 patients (78%) received combined external-beam radiation therapy and brachytherapy. Median dose of radiation to the recurrence was 60 Gy (range, 16-85 Gy). Overall survival was calculated by the Kaplan-Meier method. Endpoints were measured from the date of diagnosis of the vaginal recurrence. Median follow-up of survivors after recurrence was 53 months (range, 8-159 months). RESULTS: The 5-year and 10-year disease-free and overall survivals were 68% and 55%, and 53% and 40%, respectively. On multivariate analysis, age (p = 0.0242), Grade 1 or 2 vs. Grade 3 tumor (p = 0.002), and size of recurrence (p < 0.001) were significant predictors of overall survival. All patients who had Grade 3 disease were dead by 3.6 years from the time of recurrence. Five patients experienced a Grade 3 or 4 complication. CONCLUSIONS: Patients treated with radiotherapy for an isolated vaginal recurrence can be cured in over 50% the cases. Radiotherapy is well tolerated, with a low risk of complications. Factors predictive of overall survival include tumor grade, patient age at recurrence, and tumor size.     

Pilot study in the treatment of endometrial carcinoma with 3D image-based high-dose-rate brachytherapy using modified Heyman packing: clinical experience and dose-volume histogram analysis

PURPOSE: The aim of this study was to evaluate dose distribution within uterus (clinical target volume [CTV]) and tumor (gross tumor volume [GTV]) and the resulting clinical outcome based on systematic three-dimensional treatment planning with dose-volume adaptation. Dose-volume assessment and adaptation in organs at risk and its impact on side effects were investigated in parallel. METHODS AND MATERIALS: Sixteen patients with either locally confined endometrial carcinoma (n = 15) or adenocarcinoma of uterus and ovaries after bilateral salpingo-oophorectomy (n = 1) were included. Heyman packing was performed with mean 11 Norman-Simon applicators (3-18). Three-dimensional treatment planning based on computed tomography (n = 29) or magnetic resonance imaging (n = 18) was done in all patients with contouring of CTV, GTV, and organs at risk. Dose-volume adaptation was achieved by dwell location and time variation (intensity modulation). Twelve patients treated with curative intent received five to seven fractions of high-dose-rate brachytherapy (7 Gy per fraction) corresponding to a total dose of 60 Gy (2 Gy per fraction and alpha/beta of 10 Gy) to the CTV. Four patients had additional external beam radiotherapy (range, 10-40 Gy). One patient had salvage brachytherapy and 3 patients were treated with palliative intent. A dose-volume histogram analysis was performed in all patients. On average, 68% of the CTV and 92% of the GTV were encompassed by the 60 Gy reference volume. Median minimum dose to 90% of CTV and GTV (D90) was 35.3 Gy and 74 Gy, respectively. RESULTS: All patients treated with curative intent had complete remission (12/12). After a median follow-up of 47 months, 5 patients are alive without tumor. Seven patients died without tumor from intercurrent disease after median 22 months. The patient with salvage treatment had a second local recurrence after 27 months and died of endometrial carcinoma after 57 months. In patients treated with palliative intent, symptom relief was achieved. No severe acute and late side effects (Grade 3/4) were observed. CONCLUSIONS: Sectional image-based three-dimensional treatment planning on computed tomography and magnetic resonance imaging is feasible in definitive brachytherapy of endometrial carcinoma and enables by the use of dwell time and location adaptation a sufficient coverage of GTV and major parts of CTV. Local control in this limited number of patients is excellent and rate of side effects minimal.     

Combination of external beam irradiation and high-dose-rate intraluminal brachytherapy for inoperable carcinoma of the extrahepatic bile ducts

PURPOSE: To assess the feasibility and therapeutic benefits of a combination of external beam radiotherapy (EBRT) and high-dose-rate intraluminal brachytherapy (ILBT) for treating patients with inoperable carcinoma of the extrahepatic bile ducts. METHODS AND MATERIALS: Of 31 patients who received RT at the Yonsei Cancer Center, Yonsei University College of Medicine in Seoul, Korea between 1986 and 1995, 17 patients underwent EBRT alone (Group 1) and 14 patients were treated with EBRT in combination with high-dose-rate ILBT (Group 2). After external drainage, EBRT was delivered with a total dose ranging from 36 to 55 Gy (median 50.4) in both groups. High-dose-rate ILBT for the patients in Group 2 was performed using a high-intensity (192)Ir source (Gamma-med remote afterloading system) within the expandable intrabiliary prosthesis (Gianturco stent), inserted transhepatically at the site of the obstruction. The radiation dose of the high-dose-rate ILBT was prescribed at 1.5 cm from the center of the source with a single daily dose of 5 Gy to a total of 15 Gy given in three fractions. The response rate, patterns of treatment failure, treatment morbidity, and survival data in the two groups were compared. RESULTS: Although locoregional recurrence was the most common pattern of failure in both groups, no statistically significant difference was found in the recurrence rates between those who did and did not receive ILBT (53% for Group 1 vs. 36% for Group 2; p > 0.05). However, a prolongation of the median time to tumor recurrence was observed in the Group 2 patients (5 months for Group 1 vs. 9 months for Group 2; p = 0.06). When the EBRT dose delivered was >50 Gy, most patients experienced various degrees of GI symptoms, but the frequency of radiation-induced complications in the two groups was similar. No enhancement in treatment morbidity was attributed to the addition of high-dose-rate ILBT to EBRT. With a median follow-up of 12 months, the overall actuarial 2-year survival rate for Group 2 patients was significantly better than that for Group 1 patients (0% for Group 1 vs. 21% for Group 2; p = 0.015). CONCLUSION: Given these observations, we believe that the combined use of EBRT and high-dose-rate ILBT is a beneficial, relatively safe, and effective method of improving the treatment outcome in selected patients with inoperable carcinoma of the extrahepatic bile ducts.     

Two fractions of high-dose-rate brachytherapy in the management of cervix cancer: clinical experience with and without chemotherapy

PURPOSE: In recent years, high-dose-rate brachytherapy has become popular in the management of carcinoma of the uterine cervix, because it eliminates many of the problems associated with low-dose-rate brachytherapy. However, the optimum time-dose-fractionation remains controversial. Two fractions of high-dose-rate brachytherapy are convenient for patients, but most radiation oncologists in the United States do not use them, because of fear that they could lead to excessive rectal or bladder toxicity. Here we present our experience, which suggests that a two-fraction regimen is indeed safe and effective. METHODS: We treated 49 patients with Stages I-III biopsy-proven carcinoma of the uterine cervix by external beam radiation therapy (EBRT), plus two fractions of high-dose-rate brachytherapy. The histology was squamous cell carcinoma in 43 patients (88%) and nonsquamous in 6 (12%). The median size of the primary tumor was 6 cm (range: 3-10 cm). Each patient received EBRT to the pelvis to a median dose of 45 Gy (range: 41.4-50.4 Gy), followed by a parametrial boost when indicated. Thirty patients (61%) also received irradiation to the para-aortic lymph nodes to a dose of 45 Gy. After EBRT, each patient underwent two applications of high-dose-rate brachytherapy, 1 week apart. The dose delivered to point A was 9 Gy per application for 49 applications (50%) and 9.4 Gy for 43 applications (44%), and it varied from 7 to 11 Gy for the rest (6%). The total dose to the rectum from both high-dose-rate brachytherapy applications ranged from 4.7 to 11.7 Gy (median: 7.1 Gy), and the total dose to the bladder from 3.8 to 15.5 Gy (median: 10.5 Gy). Twenty-five of the 49 patients (51%) received concomitant chemotherapy (cisplatin 20 mg/m(2)/day for 5 days) during the first and fourth weeks of EBRT and once after the second high-dose-rate brachytherapy application. Chemotherapy was not assigned in a randomized fashion. The use of chemotherapy increased during the time period spanned by this study as increasing evidence supporting the use of chemotherapy began to appear. RESULTS: The observed survival rates after 2, 3, and 5 years were 83%, 78%, and 78%, respectively. The surviving patients have been followed up for a median of 3 years (range: 2-6 years). Eight of the 49 patients suffered local failures. Among patients treated without chemotherapy, the 3-year local control rate was 77%; it was 88% among those receiving chemotherapy. There have been no regional failures. Four patients developed distant metastases. At 3 years, 91% of the patients in each group were free of distant metastases. Ten of the 49 patients (20%) suffered Grade 3 acute toxicity; 11 (22%) had Grade 4. Among the 24 patients treated without chemotherapy, only 1 (4%) suffered Grade 3 toxicity. Among the 25 patients receiving chemotherapy, in contrast, 8 (32%) suffered Grade 3 and 12 (48%) Grade 4 acute toxicity. Only 2 patients suffered late toxicity: One suffered Grade 2 and the other Grade 3 late toxicity. The actuarial risk of Grade 2 or worse late toxicity was 5%, with or without chemotherapy. CONCLUSIONS: Our experience suggests that two fractions of high-dose-rate brachytherapy are safe and effective in the management of cervix cancer, even in conjunction with concomitant cisplatin. The fears that the use of two fractions would lead to excessive rectal or bladder toxicity proved unfounded. Guidelines for ensuring a low complication rate are discussed.     

The safety and usefulness of high-dose-rate endoluminal brachytherapy as a boost in the treatment of patients with esophageal cancer with external beam radiation with or without chemotherapy

PURPOSE: This study reports the results of a single-institution experience with high-dose-rate brachytherapy (HDRBT) used as a boost in the treatment of esophageal cancer with external beam radiation therapy (ERT) with or without chemotherapy. METHODS AND MATERIALS: Patients without evidence of metastatic disease were identified. HDRBT was given before ERT with a dose of 20 Gy in 5 fractions. Patients with a Karnofsky performance of more than 70 received treatment with 50 Gy in 25 fractions and concurrent 5-fluorouracil and cis-platinum during Weeks 1 and 5, whereas patients with a Karnofsky performance of less than 70 were treated with radiation therapy alone with 35 Gy in 14 fractions. RESULTS: Fifty-three patients received HDRBT treatment with combined ERT and chemotherapy and 17 patients with ERT alone. The incidence of acute bone marrow toxicity was 55% Grade 2 and 15% Grade 3, and 85% of patients had Grade 2 esophagitis. With a median follow-up time of 26 months, the median survival was 21 months; the 2-year local recurrence was 25%, and the 5-year survival rate was 28%. CONCLUSION: HDRBT is safe and beneficial for local control in the radical treatment of patients with esophageal cancer.     

Definitive Concurrent Chemoradiotherapy in Cervical Cancer - a University of Malaya Medical Centre Experience

Background: The efficacy of concurrent chemoradiotherapy in the treatment of locally advanced cervical canceris well established. We aimed to investigate the long-term efficacy of definitive concurrent chemoradiotherapyfor cervical cancer in the University of Malaya Medical Centre. Materials and Methods: A cohort of 60 patientswith FIGO stage IB2-IVA cervical cancer who were treated with definitive concurrent chemoradiotherapywith cisplatin followed by intracavitary brachytherapy or external beam radiotherapy (EBRT) boost betweenNovember 2001 and May 2008 were analysed. Patients were initially treated with weekly intravenous cisplatin(40mg/m2) concurrent with daily EBRT to pelvis of 45-50Gy followed by low dose rate brachytherapy or EBRTboost to tumour. Local control rate, progression free survival, overall survival and treatment related toxicitiesgraded by the RTOG criteria were evaluated. Results: The mean age was 56. At the median follow-up of 72months, the estimated 5-year progression-free survival (PFS) (median PFS 39 months) and the 5-year overallsurvival (OS) (median OS 51 months) were 48% and 50% respectively. The 5-year local control rate was 67.3%.Grade 3-4 late gastrointestinal and genitourinary toxicity occurred in 9.3% of patients. Conclusions: The 5-yearPFS and the 5-year OS in this cohort were lower than in other institutions. More advanced stage at presentation,longer overall treatment time (OTT) of more than fifty-six days and lower total dose to point A were the potentialfactors contributing to a lower survival.     

Dosimetric parameters that predict late rectal complications after curative radiotherapy in patients with uterine cervical carcinoma

BACKGROUND: Late rectal complication (LRC) was a major late complication in patients with uterine cervical carcinoma who were treated with a combination of external beam radiotherapy (EBRT) and high-dose-rate intracavitary irradiation (HDR-ICR). For the current study, the authors retrospectively evaluated dosimetric parameters that were correlated with LRC > or = Grade 2 in patients with uterine cervical carcinoma who were treated with curative radiotherapy, and they analyzed the appropriate dose estimates to the rectum that were predictive for LRC > or = Grade 2. METHODS: Between July 1994 and September 2002, 157 patients who were diagnosed with Stage IB-IIIB cervical carcinoma and were treated with definitive radiotherapy were included. EBRT (41.4-66 grays [Gy] in 23-33 fractions) to the whole pelvis was delivered to all patients, with midline shielding performed after a 36-50.4 Gy external dose. HDR-ICR (21-39 Gy in 6-13 fractions to Point A) was administered at a rate of 2 fractions weekly after midline shielding of EBRT. LRC was scored using Radiation Therapy Oncology Group criteria. The total biologically effective dose (BED) at specific points, such as Point A (BED(Point A)), rectal point (BED(RP)), and maximal rectal point (BED(MP)), was determined by a summation of the EBRT and HDR-ICR components, in which the alpha/beta ratio was set to 3. Analyzed parameters included patient age, tumor size, stage, concurrent chemotherapy, ICR fraction size, RP ratio (dose at the rectal point according to the Point A dose), MP ratio (dose at the maximal rectal point according to the Point A dose), EBRT dose, BED(Point A), BED(RP), and BED(MP). RESULTS: The 5-year actuarial overall rate of LRC > or = Grade 2 in all patients was 18.4%. Univariate analysis showed that the RP ratio, MP ratio, EBRT dose, BED(Point A), BED(RP), and BED(MP) were correlated with LRC > or = Grade 2 (P < 0.05). Multivariate analysis showed that, of all clinical and dosimetric parameters evaluated, only BED(RP) was correlated with LRC > or = Grade 2 (P = 0.009). The 5-year actuarial rate of LRC > or = Grade 2 was 5.4% in patients with a BED(RP) < 125 Gy(3) and 36.1% in patients with a BED(RP) > or = 125 Gy(3) (P < 0.001). CONCLUSIONS: BED(RP) was a useful dosimetric parameter for predicting the risk of LRC > or = Grade 2 and should be limited to < 125 Gy(3) whenever possible to minimize the risk of LRC > or = Grade 2 in patients with uterine cervical carcinoma who are treated with a combination of EBRT and HDR-ICR. Cancer 2005.     

Use of individual fraction size data from 3756 patients to directly determine the alpha/beta ratio of prostate cancer

PURPOSE: To examine the effect of fraction size and total dose of radiation on recurrence of localized prostate cancer. METHODS AND MATERIALS: A total of 3756 patients treated with radiation monotherapy at three institutions were analyzed, including 185 high-dose-rate brachytherapy (HDRB) boost patients. The 5th to 95th centiles of external beam radiotherapy (EBRT) fraction sizes and doses were 1.8 to 2.86 Gy, and 57.4 to 77.4 Gy, respectively, and HDRB fractional doses were between 5.5 and 12 Gy, totaling 147 unique fractionation schedules. Failure was defined by one biochemical (nadir + 2 ng/ml) and two advanced disease endpoints. The alpha/beta ratios were estimated via a proportional hazards model stratified by risk severity and institution. RESULTS: The alpha/beta ratio using biochemical recurrence was 3.7 Gy (95% confidence interval [95% CI], 1.1, infinity Gy) for EBRT-only cases and 2.6 Gy (95% CI, 0.9, 4.8 Gy) after the addition of HDRB data. This estimate was highly dependent on an HDRB homogeneity correction factor (120% HDRB dose increase; alpha/beta ratio 4.5 Gy, 95% CI 1.6, 8.7 Gy). A 5-Gy increase in total dose reduced the hazard of failure by 16% (95% CI 11, 21%, p < 0.0001), and had more impact as follow-up matured (p < 0.0003). The clinically advanced endpoints concurred with the biochemical failure results, albeit with less precision. CONCLUSIONS: This study supports the concept that the alpha/beta ratio of prostate cancer is low, although considerable uncertainty remains in the estimated value. Outcome data from EBRT studies using substantially higher doses per fraction are needed to show increased precision in these estimates.     

Interim report of image-guided conformal high-dose-rate brachytherapy for patients with unfavorable prostate cancer: the William Beaumont phase II dose-escalating trial

PURPOSE: We analyzed our institution's experience treating patients with unfavorable prostate cancer in a prospective Phase II dose-escalating trial of external beam radiation therapy (EBRT) integrated with conformal high-dose-rate (HDR) brachytherapy boosts. This interim report discusses treatment outcome and prognostic factors using this treatment approach. METHODS AND MATERIALS: From November 1991 through February 1998, 142 patients with unfavorable prostate cancer were prospectively treated in a dose-escalating trial with pelvic EBRT in combination with outpatient HDR brachytherapy at William Beaumont Hospital. Patients with any of the following characteristics were eligible: pretreatment prostate-specific antigen (PSA) >/= 10.0 ng/ml, Gleason score >/= 7, or clinical stage T2b or higher. All patients received pelvic EBRT to a median total dose of 46.0 Gy. Pelvic EBRT was integrated with ultrasound-guided transperineal conformal interstitial iridium-192 HDR implants. From 1991 to 1995, 58 patients underwent three conformal interstitial HDR implants during the first, second, and third weeks of pelvic EBRT. After October 1995, 84 patients received two interstitial implants during the first and third weeks of pelvic EBRT. The dose delivered via interstitial brachytherapy was escalated from 5.50 Gy to 6.50 Gy for each implant in those patients receiving three implants, and subsequently, from 8.25 Gy to 9.50 Gy per fraction in those patients receiving two implants. To improve implant quality and reduce operator dependency, an on-line, image-guided interactive dose optimization program was utilized during each HDR implant. No patient received hormonal therapy unless treatment failure was documented. The median follow-up was 2.1 years (range: 0.2-7.2 years). Biochemical failure was defined according to the American Society for Therapeutic Radiology and Oncology Consensus Panel definition. RESULTS: The pretreatment PSA level was >/= 10.0 ng/ml in 51% of patients. The biopsy Gleason score was >/= 7 in 58% of cases, and 75% of cases were clinical stage T2b or higher. Despite the high frequency of these poor prognostic factors, the actuarial biochemical control rate was 89% at 2 years and 63% at 5 years. On multivariate analysis, a higher pretreatment PSA level, higher Gleason score, higher PSA nadir level, and shorter time to nadir were associated with biochemical failure. In the entire population, 14 patients (10%) experienced clinical failure at a median interval of 1.7 years (range: 0.2-4.5 years) after completing RT. The 5-year actuarial clinical failure rate was 22%. The 5-year actuarial rates of local failure and distant metastasis were 16% and 14%, respectively. For all patients, the 5-year disease-free survival, overall survival, and cause-specific survival rates were 89%, 95%, and 96%, respectively. The 5-year actuarial rate of RTOG Grade 3 late complications was 9% with no patient experiencing Grade 4 or 5 acute or late toxicity. CONCLUSION: Pelvic EBRT in combination with image-guided conformal HDR brachytherapy boosts appears to be an effective treatment for patients with unfavorable prostate cancer with minimal associated morbidity. Our dose-escalating trial will continue.     

Three-dimensional conformal radiotherapy for locoregionally recurrent lung carcinoma after external beam irradiation: a prospective phase I-II clinical trial

OBJECTIVES: To observe in a clinical trial the feasibility, tolerance, and efficacy of reirradiation by three-dimensional conformal radiotherapy (3D-CRT) for locoregionally recurrent lung carcinoma after external beam radiotherapy (EBRT). MATERIALS AND METHODS: Between June 1999 and March 2001, 23 lung carcinoma patients with locoregional recurrence after EBRT were enrolled in this study. Of the 23 patients, 21 were men and 2 were women (median age 68 years, range 43-79). At the first course of RT, 9 patients had squamous cell carcinoma, 7 adenocarcinoma, and 7 small cell carcinoma. The interval between the first course of RT and recurrence varied from 6 to 42 months (median 13). The median dose of the first course of RT was 66 Gy (range 30-78). Reirradiation was carried out using 3D-CRT and only covered the radiographic lesions. The median dose of reirradiation was 51 Gy (range 46-60), which was delivered by a conventionally fractionated schedule (i.e., 1.8-2.0 Gy/fraction, 5 fractions/wk). The toxicity was assessed according to the Radiation Therapy Oncology Group criteria. RESULTS: The median follow-up time was 15 months (range 2-37). Acute radiation esophagitis occurred in 9% of patients (Grade 1-2). Acute radiation pneumonitis developed in 22% of patients (Grade 1-2). No cases of acute Grade 3 or greater toxicity had been recorded at last follow-up. Pulmonary fibrosis was observed in 26% of patients (Grade 2-3); no other severe late complications have been observed. The 1- and 2-year survival rate was 59% and 21%, respectively. The locoregional progression-free rate at 1 and 2 years was 51% and 42%, respectively. CONCLUSIONS: Reirradiation using 3D-CRT was tolerated by this group of recurrent lung carcinoma patients without severe complications. The 2-year outcome was encouraging. Reirradiation with 3D-CRT can be considered an option for the management of locoregionally recurrent lung carcinoma.     

Use of stereotactic body radiation therapy for medically inoperable multiple primary lung cancer

Introduction: To review outcomes of medically inoperable patients treated with stereotactic body radiation therapy (SBRT) for multiple primary lung cancer (MPLC). Methods: We retrospectively reviewed the charts of 10 patients (21 lesions) treated with SBRT for synchronous (seven), metachronous (one) or synchronous/metachronous lung cancers. All patients were male, medically inoperable and had a median age of 66 years. Eight patients had bilateral disease and two had unilateral disease. All patients had a histological diagnosis in at least one of the two lesions and four patients (44.4%) had both lesions biopsied. There were 18 T1 lesions and three T2 lesions. SBRT was in three fractions of 20 Gy or five fractions of 11–12 Gy to each lesion. Results: Mean and median follow up were 18.8 and 15.5 months, respectively. At analysis, six patients (60.0%) are alive, and five of these living patients (83.3%) have no evidence of disease recurrence or progression. Four patients (44.4%) developed distant metastatic disease. Twenty lesions (95.2%) achieved in‐field local control. No patients experienced acute pulmonary complications and only two patients (22.2%) experienced late grade I lung toxicity as per the Radiation Therapy Oncology Group toxicity criteria. Conclusion: SBRT for MPLC in medically inoperable patients is a safe, feasible and effective treatment approach.     

Results of low- and high-dose-rate interstitial brachytherapy for T3 mobile tongue cancer.

PURPOSE: To evaluate the treatment results of low-dose-rate (LDR) and high-dose-rate (HDR) interstitial brachytherapy (ISBT) for T3 mobile tongue cancer. MATERIAL AND METHODS: Between 1974 and 1992, 61 patients with T3 mobile tongue cancer were treated with LDR ISBT using (192)Ir hairpins with or without single pins. In addition, between 1991 and 1999, 14 patients were treated with HDR ISBT. For nine patients treated with ISBT alone, the total dose was 59-94 Gy (median 72 Gy) within one week in LDR ISBT and 60 Gy/10 fractions/5 days in HDR ISBT. For 66 patients treated with a combination therapy of external beam radiotherapy (EBRT) and ISBT, the total dose was 12.5-60 Gy (median 30 Gy) of EBRT and 50-112 Gy (median 68 Gy) within 1 week in LDR ISBT or 32-60 Gy (median 48 Gy)/8-10 fractions/5-7 days in HDR ISBT. RESULTS: The 2- and 3-year local control rates of all patients were both 68%. The 2- and 3-year local control rates of patients treated with LDR ISBT were both 67%, and those with HDR ISBT were both 71%. The local control rate of patients treated with HDR ISBT was similar to those with LDR ISBT. CONCLUSIONS: ISBT for T3 mobile tongue cancer is effective and acceptable. The treatment result of HDR ISBT is almost similar to that of LDR ISBT for T3 mobile tongue cancer.     

External beam radiotherapy for primary and adjuvant management of aggressive fibromatosis

PURPOSE: To review a large single-institution experience in the management of aggressive fibromatosis to determine the effectiveness of external beam radiotherapy (EBRT) and identify the presentation and treatment variables predictive of locoregional control. METHODS AND MATERIALS: Between 1975 and 2000, 72 patients were treated with EBRT for a pathologically confirmed diagnosis of aggressive fibromatosis. Thirty patients were treated at the primary presentation and 42 at the time of a locoregional recurrence. Minimal 2-year follow-up data were available for 65 patients (median 6 years). Megavoltage irradiation with 60Co to 20 MV photons or electron therapy was used for all patients. Most patients were treated after attempted complete surgical resection; 16 patients underwent pretreatment biopsy alone. The prescribed treatment was standard (1.8 Gy) daily fractions in 42 cases and 1.2 Gy fractions b.i.d. in 23 cases. The median prescribed dose was 54 Gy. The prognostic variables and treatment results were evaluated by Kaplan-Meier actuarial analysis. RESULTS: Locoregional control was achieved in 52 of 65 patients. The 5-year actuarial locoregional control was 83%. Locoregional failure occurred in 13 patients (11 in patients with recurrent tumors). Only two failures occurred within the irradiation fields; nine failures occurred at the field margins. Eleven patients were salvaged by surgery: wide excision in nine and amputation in two. The only prognostic factor significant for locoregional control was primary vs. recurrent presentation (p = 0.0193). The 5-year locoregional control rates for irradiation at initial presentation and at recurrence were 96% and 75%, respectively. The variables without significance for locoregional control included primary tumor location, surgical procedures performed, resection margins, and gross vs. microscopic residual tumor at irradiation. Lymphedema was the most common late effect, occurring in 7 patients, 5 with prior treatment. Bone fracture occurred in 3 patients; all 3 had fibromatosis involving the bone at presentation but without recurrence at the time of fracture. CONCLUSION: EBRT is effective treatment for aggressive fibromatosis. The probability of locoregional control decreases with multiple prior recurrences.     

Long-term outcomes of definitive external-beam radiotherapy for non-metastatic castration-resistant prostate cancer

Background

Although definitive external-beam radiotherapy (EBRT) is one of the treatment options for non-metastatic castration-resistant prostate cancer (NM-CRPC), there are limited data on the long-term outcomes of this treatment.

Methods

We retrospectively evaluated 31 NM-CRPC patients consecutively treated with definitive EBRT. The median age was 74 years upon EBRT initiation. The initial T stage distribution was as follows: T1c in 3, T2 in 11, T3 in 14, and T4 in 3 cases, respectively. The median prostate dose was 70.4 Gy. A castration-resistant status was defined as continuously increasing serum prostate-specific antigen levels despite ongoing hormonal therapy (HT).

Results

The median follow-up duration after EBRT was 66.6 months. The median period of primary HT was 18.0 months. The 5- and 8-year overall survival rates were 74.6 and 49.8%, respectively. The 5- and 8-year prostate cancer-specific survival rates were 77.4 and 51.7%, respectively. Fourteen patients died, and prostate cancer was the cause of death in 12 of these patients. The 5- and 8-year relapse-free survival rates were 32.3 and 25.8%, respectively. Among 23 patients who experienced biochemical or clinical failure, the median duration to recurrence after EBRT was 19.3 months. The 5- and 8-year clinical failure-free survival rates were 56.0 and 51.4%, respectively. Among the 14 patients who experienced clinical failure, the median duration after EBRT was 16.0 months. The local relapse-free rates at 5 and 8 years were 91.0 and 91.0%, respectively. Grade 3 or higher adverse events were observed in four patients.

Conclusion

Definitive EBRT achieved a long-term disease-free and clinical failure-free status in approximately one-third of and half of the treated NM-CRPC patients, respectively. This approach was also associated with favorable local relapse-free rates and overall survival outcomes. Definitive EBRT is a promising approach for NM-CRPC patients.

     

Stereotactic body radiation therapy for nonmetastatic lung cancer: an analysis of 75 patients treated over 5 years

PURPOSE: Non-small-cell lung cancer (NSCLC) may not be medically operable even in patients with surgically resectable disease. For patients who either refuse surgery or are medically inoperable, radiation therapy may be the best therapeutic choice. Stereotactic body radiation therapy (SBRT) employs external fixation and hypofractionation to deliver a high dose per fraction of radiation to a small target volume. METHODS AND MATERIALS: Retrospective review of 75 patients treated over 5 years at Staten Island University Hospital as definitive treatment for NSCLC or presumed NSCLC. Patients received a median of 5 fractions of 8 Gy per fraction over 27 days. RESULTS: Overall 1-, 2-, and 5-year actuarial survivals were 63%, 45%, and 17%. Patients with a gross tumor volume (GTV) less than 65 cm3 enjoyed a longer median survival (25.7 vs. 9.9 months, p < 0.003), and at 5 years, the actuarial survival for the patients with GTVs less than 65 cm3 was 24% vs. 0% for those with GTVs larger than 65 cm3. CONCLUSIONS: Stereotactic body radiation therapy as delivered was ineffective for curing the patients whose GTVs were larger than 65 cm3. SBRT was promising for those with GTVs less than 65 cm3.     

Stereotactic body radiotherapy for bilateral primary lung cancers: the Indiana University experience

PURPOSE: To review the outcomes of 10 patients treated with stereotactic body radiotherapy for bilateral primary medically inoperable lung cancer. METHODS AND MATERIALS: Between July 2001 and February 2005, 10 patients were treated at Indiana University with stereotactic body radiotherapy for bilateral multiple primary lung cancers using a stereotactic body frame (Elekta, Stockholm, Sweden). Nine patients had cancers that were deemed inoperable secondary to multiple medical comorbidities. One patient refused surgery. All patients had biopsy proven non-small-cell lung carcinoma of at least one of their masses and presented with either metachronous or synchronous pulmonary nodules. Positron emission tomography scans were done for all patients before treatment. Radiation dose varied between 4800 and 6600 cGy given in 3 fractions prescribed to the 80% line covering at least 95% of the planning target volume. We performed a retrospective review of the outcome of these patients. RESULTS: The mean follow-up time was 20.7 months and the median time was 18.5 months (range, 7-42 months). At the time of this review, all 10 patients were living. Eight (80%) of 10 patients had no evidence of disease progression. One patient developed distant metastasis 5 months after treatment and a second patient developed a local recurrence within the radiation field 11 months after treatment. Six patients had either acute or late pulmonary toxicity, but all toxicity was < or =Grade 2 as defined by the Radiation Therapy Oncology Group toxicity criteria. CONCLUSION: Our preliminary results indicate that stereotactic body radiotherapy is a possibly safe and potentially effective treatment option for patients with bilateral multiple primary lung cancers that are deemed medically inoperable.     

Ic期子宫内膜癌患者中MPA和EBRT的联合疗效

Objective: To report the comparative effect of combined medroxyprogesterone acetate (MPA) and external beam pelvic radiotherapy (EBRT) with EBRT alone on local or distant recurrences, overall survival and treatment related toxicities in patients with stage Ic grade 3 endometrial cancer. Methods: A retrospective review of 80 International Federation of Gyne-cology and Obstetrics (FIGO) stage Ic grade 3 endometrial carcinoma patients treated between October 1994 and October 2004 at Renmin Hospital, Wuhan University, China was performed. All patients underwent surgery, of which 40 patients in arm I received combined MPA and EBRT while in arm II 40 patients received only adjuvant EBRT after surgery. The median dose of EBRT in arm I was 50 Gy (range 36-54 Gy) and in arm II was 45.2 Gy (range 43.2-50.4 Gy). Multivariate analysis was performed for the prognostic factors and Kaplan-Meier method was used for overall survival. Results: Of the 80 eligible patients, 40 in each group could be evaluated. The follow-up times ranged from 4-98 months with a median of 45 months. The overall survival rates at five years were 73% among patients treated with combined MPA and EBRT and 28.2% among patients treated with EBRT alone (P < 0.001). The rate of distant metastasis was significantly higher among patients treated with EBRT alone group than combined MPA and EBRT (55% vs 25%, P = 0.006) while no difference in loco regional recur-rence rates was observed in both treatment groups. Most of the side effects observed in the combined MPA and EBRT group. Age (P < 0.001) and the presence of progesterone receptors (P = 0.003) were independent significant prognostic factors for overall survival in multiple regression analysis. Conclusion: We has been concluded that the addition of progestagen to external beam pelvic radiotherapy significantly improved survival and reduced distant metastasis among women with stage Ic grade 3 endometrial cancer.     

射波刀治疗早期周围型肺癌结果的初步分析

目的 评价采用射波刀(Cyberknife)立体定向放射手术平台治疗早期周围型肺癌患者的疗效和初期毒性反应.方法 接受射波刀治疗的17例周围型肺癌患者年龄54～87岁,临床分期Ⅰa期(T1N0M0期)8例、Ⅰ b期(T2N0M0期)9例,病理类型鳞癌3例、腺癌8例(6例因拒绝穿刺等以PET-CT为诊断依据).肺癌计划靶体积6～82 cm3,中位36 cm3,总剂量45～60 Gy,中位剂量50 Gy,分割3～5次.10例采用肿瘤内植入金标的呼吸同步追踪技术(Synchrony),7例采用椎体追踪(X-Sight)技术.结果 所有患者治疗耐受性良好,主要不良表现为乏力.疗后2～10个月中(中位时间7个月),17例均存活.影像学复查结果为13例完全缓解,4例部分缓解,未发现肿瘤进展、复发及远处转移.出现放射性肺炎1级3例、2级1例,骨髓抑制1级3例,经对症处理后好转.结论 采用射波刀进行立体定向放射治疗周围型肺癌疗效显著,安全性好,远期结果需进一步随访.