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Radiation therapy in the treatment of advanced endometrial carcinoma
Proceedings of the 46th Annual ASTRO Meeting
1084
Can High-Dose-Rate Brachytherapy be an Alternative to Surgery in Selected Patients with Stage I Endometrial Carcinoma
T. M. Niazi,1 L. Souhami,1 G. W. Stanimir,2 L. Portelance,1 B. Bahoric1 Radiation Oncology, McGill, Montreal , QC, Canada, 2Gynecology Oncology, McGill, Montreal , QC, Canada
1
Purpose/Objective: Total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAHBSO) is the gold standard for patients with endometrial carcinoma. However, patients with high operative risks are usually treated with radiation therapy alone. The goal of this study was to review our experience of High-Dose-Rate Brachytherapy (HDRB) with or without external-beam irradiation (EBRT) for such patients. Materials/Methods: Between 1984 and 2003, 38 patients with clinical stage I and II histologically proven adenocarcinoma of the endometrium, who were considered high operative risk, received radiotherapy (RT) as the primary treatment. The median age at presentation was 74.1 years. 29 patients (76%) were diagnosed with stage I and 9 patients (24%) with Stage II. There were 21 patients (55%) with grade I, 11 (29%) with grade II, and 6 (16%) with grade III histology. The local extent of the disease was assessed by exam under anesthesia (EUA) prior to 1996 and MRI and EUA thereafter. Eight patients (21%) were treated with combined HDRB and EBRT and 30 patients (79%) with HDRB alone. Six of the patients treated with combined modality were stage II and two were stage I. The median HDRB dose was 2390 cGy (range 1000 –3400 cGy) prescribed to a point 2 cm from the midline. The treatment was delivered in one to three fractions in a weekly schedule. HDRB was performed under spinal anesthesia on an outpatient basis. The median EBRT dose was 4200 cGy (range 4000 cGy-4600 cGy). Follow-up was performed every 3 months for 3 years, and every 6 months thereafter. Results: At a median follow-up of 36 months (range 10 to 206 months), 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 failure. Six stage II patients (67%) and 5 stage I patients (17%) experienced failure. Similarly, grade II and III accounted for 72% of the relapses. The actuarial 15 year disease specific survival (DSS) was 81 % for all stages, 93% for stage I and 42% for stage II. The actuarial 15 year DSS was 91% for Grade I, and 67% for Grade II and III combined (p ⫽ 0.0254). The actuarial 15 year DSS was 92% for stage I grade I patients and 63% for the remaining patients (p ⫽ 0.0107). 13 patients (34%) received a dose of 3000 cGy, all with stage I disease. Four of these patients had grade III while the rest had grade I disease. The actuarial 15 year DSS in this group was 100% versus 71% for patients with less than 3000 cGy. No complications were encountered during HDRB. Acute toxicities were limited to grade I-II that occurred in three patients (8%). Four patients experienced late toxicities, one grade II (3%) and 3 (8%) grade III and IV. Conclusions: Medically inoperable stage I endometrial carcinoma may be safely treated with HDRB as the primary treatment. In selected stage I patients our results are equivalent to that of surgery. We believe that the alternative option of HDRB as the primary treatment for selected stage I endometrial carcinoma, even in patients with low operative risks, needs further evaluation.
1085
Radiation Therapy in the Treatment of Advanced Endometrial Carcinoma
J. T. Payne, J. Yoneda, M. Mohiuddin, A. Meigooni, U. Malik Department of Radiation Medicine, University of Kentucky, Lexington, KY Purpose/Objective: The treatment of stage I and II endometrial carcinoma with external beam radiotherapy with or without brachytherapy boost resulting in a local recurrence rate of approximately 4% has been well established. Studies looking at recurrence in high risk endometrial cancer have concentrated on reducing distant failure with whole abdominal radiotherapy. However there remains a large percentage of patients with advanced disease who fail locally. The goal of this retrospective study was to determine differences in the local failure rate in patients with early and high risk endometrial cancer. Materials/Methods: Between January 1996 and February 2003, 101 patients with FIGO stage IB through IIIC endometrial cancer treated with radiotherapy were evaluated. Patients with endometrial adenocarcinoma with papillary serous, clear cell or MMMT histology were excluded from the analysis. Patients who were initially treated for recurrent endometrial cancer were also excluded. This resulted in 31 evaluable patients of which 24 had FIGO stage I and II disease and 7 had FIGO stage III disease. The group of patients with FIGO stage III disease consisted of one stage IIIA, one stage IIIB, and 5 stage IIIC patients.
S307
S308
I. J. Radiation Oncology
● Biology ● Physics
Volume 60, Number 1, Supplement, 2004
These patients were treated with doses of external beam radiotherapy to the whole pelvis ranging from 4500 to 4560 cGy. Total doses to affected lymph nodes ranged from 4500 to 7020 cGy. Brachytherapy boosts were given in all cases and ranged from 700 to 2100 cGy (mean 1412 cGy) Follow-up for all patients ranged from 13 to 90 months. Results: In the group of patients with FIGO stage I and II disease, one patient developed local recurrence (4%) and a second developed distant disease (4%). In the group of seven patients with high risk disease (FIGO stage III), there were three failures (43%). One patient died of metastatic disease, one developed local (vaginal apex) recurrence and later distant disease and the third was found to have vaginal apical recurrence and lymph node involvement. The vaginal apical recurrence rate in the high risk group was 2 of 7 patients (29%). The difference in vaginal apex recurrence between the FIGO stage I, II group and the stage III group approached significance with a p value of 0.055. Conclusions: The differences in vaginal apex recurrence between the FIGO stage I, II group and the FIGO stage III group suggest that radiation doses to the vaginal apex may need to be escalated via brachytherapy to improve local control for high risk endometrial cancer patients.
1086
Combination High-Dose-Rate Brachytherapy and External Beam Radiation Therapy for the Treatment of Primary Vaginal Cancer: 5-Year Results
Y. E. Lieskovsky,1 D. Demanes2 Radiation Oncology, Stanford University, Stanford, CA,
1
2
, California Endocurietherapy Cancer Center, Oakland, CA
Purpose/Objective: To report the outcome of high-dose-rate (HDR) brachytherapy and external beam radiation therapy (EBRT) for vaginal carcinoma. Materials/Methods: A total of 54 patients received HDR brachytherapy for primary vaginal carcinoma between September 1991 and December 2001 were analyzed. FIGO stages I-IV were found in 6, 41, 6, and 1 patients, respectively. Histology was adenocarcinoma, adenosquamous carcinoma, and squamous cell carcinoma in 11, 1, and 42 patients. EBRT was delivered to 52 patients; it consisted of 36 Gy to the pelvis and 50.4 Gy to the pelvic sidewalls with a midline block introduced at 36 Gy, cut to match the 100% brachytherapy isodose line. Eight patients with lower vaginal lesions received 50.4 Gy EBRT to bilateral inguinal nodes. HDR brachytherapy was administered in 6 fractions 5.5 Gy to a total dose of 33 Gy. Early stages of disease (Stages I-II) were treated with 6 intracavitary HDR applications (twice a week for 3 weeks) alone (n ⫽ 1) or combined with external beam therapy (n ⫽ 9), whereas more advanced diseases (Stages II-IV) was treated with interstitial HDR brachytherapy (two implants a week apart with 3 fractions per implant) alone (n ⫽ 1) or combined with EBRT (n ⫽ 44). Eight patients received chemotherapy with Cisplatinum and 5-FU. Results: Mean follow-up was 45 months. Local control rate was 87% (7/54), pelvic control rate was 85% (9/54), distant metastatisis rate was 15% (8/54). Five-year overall survival rate for all patients was 52% and disease-free survival was 69%. Of the 14 patients who died of disease, 6 had pelvic failure only, 5 had distant failure only, and 3 had pelvic and distant failure. There was a 7% incidence of Grade 3 RTOG late gynecologic morbidity (4 cases of vaginal necrosis that resolved completely with hyperbaric oxygen treatment). There was a 7% incidence of Grade 4 GI/GU morbidity (1 case of a vesico-vaginal fistula, 2 cases of recto-vaginal fistula, and 1 case of small bowel obstruction requiring permanent ileostomy). Conclusions: HDR brachytherapy is an effective and well-tolerated treatment for cancer of the vagina that results in preservation of bowel and bladder function in most cases.
1087
Risk Factors Associated with Incomplete Brainstem Recovery Following Post-Operative Conformal Radiation Therapy for Infratentorial Ependymoma
R. M. Chitti,1 R. B. Khan,1 X. Xiong,2 T. E. Merchant1 Radiological Sciences, St. Jude Children’s Research Hospital, Memphis, TN, 2Biostatistics, St. Jude Children’s Research Hospital, Memphis, TN 1
Purpose/Objective: Identify risk factors associated with incomplete brainstem recovery in pediatric patients with infratentorial ependymoma who received post operative conformal radiation therapy (54 –59.4Gy) and determine the effect of radiation dose on brainstem function. Materials/Methods: The study group included 66 patients (median age 2.6yrs ⫾ 3.8yrs) followed more than 6 months post irradiation (median 36 months, range 7–76 months) and assessed for brainstem function by neurological examination of cranial nerves V-VII and IX-XII, motor weakness and dysmetria. Patients were divided into three groups representing normal baseline and follow-up (NL, n ⫽ 17), abnormal baseline and full recovery at last follow-up (FR, n ⫽ 13), abnormal baseline with partial recovery at last follow-up (PR, n ⫽ 35), and progressive deficits (PD, n ⫽ 1). Patient grouping was correlated with clinical and treatment related factors including age at time of irradiation, extent and number of surgical procedures, hydrocephalus, CSF shunting, number of CSF shunting procedures, gross tumor volume (GTV), planning target volume (PTV), mean brainstem dose and the percent volume of the brainstem receiving ⱖ54Gy. Patients were treated with conformal radiation therapy using an anatomically-confined clinical target volume (CTV) margin of 10mm surrounding the post-operatively defined gross tumor volume and a geometrically-expanded PTV of 3–5mm surrounding the CTV. The 100% isodose volume (⫺5%/⫹10%) encompassed the PTV. The mean brainstem dose was 54.88Gy (⫾ 4.65 Gy). Results: Risk factors associated with partial recovery included more than one surgical resection (NL 1/17 vs. FR 3/13 vs. PR 18/35, p ⫽ 0.0006), CSF shunting (NL2/17 vs. FR 2/13 vs. PR 20/35, p ⫽ 0.0004), number of CSF shunting procedures including revisions (NL 2/17 vs. FR 2/13 vs. PR 20/35; p ⫽ 0.0004), and total number of surgical resection and shunting procedures (NL⫹FR 8/30 vs. PR 24/35; p ⫽ 0.0011). Separate analysis including only patients under the age of 3 years and grouped according to NL⫹FR (n ⫽ 16) and PR (n ⫽ 25) showed more than one surgical resection (NL⫹FR 1/16 vs. PR 12/24, p ⫽ 0.0053), CSF shunting (NL⫹FR 1/16 vs. PR 14/24; p ⫽ 0.0021) , and total number of surgical resection and shunting procedures (NL ⫹ FR 2/16 vs. PR 15/24 p ⫽ 0.0028) to be associated with partial recovery. There was a statistically significant
1084
Can High-Dose-Rate Brachytherapy be an Alternative to Surgery in Selected Patients with Stage I Endometrial Carcinoma
T. M. Niazi,1 L. Souhami,1 G. W. Stanimir,2 L. Portelance,1 B. Bahoric1 Radiation Oncology, McGill, Montreal , QC, Canada, 2Gynecology Oncology, McGill, Montreal , QC, Canada
1
Purpose/Objective: Total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAHBSO) is the gold standard for patients with endometrial carcinoma. However, patients with high operative risks are usually treated with radiation therapy alone. The goal of this study was to review our experience of High-Dose-Rate Brachytherapy (HDRB) with or without external-beam irradiation (EBRT) for such patients. Materials/Methods: Between 1984 and 2003, 38 patients with clinical stage I and II histologically proven adenocarcinoma of the endometrium, who were considered high operative risk, received radiotherapy (RT) as the primary treatment. The median age at presentation was 74.1 years. 29 patients (76%) were diagnosed with stage I and 9 patients (24%) with Stage II. There were 21 patients (55%) with grade I, 11 (29%) with grade II, and 6 (16%) with grade III histology. The local extent of the disease was assessed by exam under anesthesia (EUA) prior to 1996 and MRI and EUA thereafter. Eight patients (21%) were treated with combined HDRB and EBRT and 30 patients (79%) with HDRB alone. Six of the patients treated with combined modality were stage II and two were stage I. The median HDRB dose was 2390 cGy (range 1000 –3400 cGy) prescribed to a point 2 cm from the midline. The treatment was delivered in one to three fractions in a weekly schedule. HDRB was performed under spinal anesthesia on an outpatient basis. The median EBRT dose was 4200 cGy (range 4000 cGy-4600 cGy). Follow-up was performed every 3 months for 3 years, and every 6 months thereafter. Results: At a median follow-up of 36 months (range 10 to 206 months), 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 failure. Six stage II patients (67%) and 5 stage I patients (17%) experienced failure. Similarly, grade II and III accounted for 72% of the relapses. The actuarial 15 year disease specific survival (DSS) was 81 % for all stages, 93% for stage I and 42% for stage II. The actuarial 15 year DSS was 91% for Grade I, and 67% for Grade II and III combined (p ⫽ 0.0254). The actuarial 15 year DSS was 92% for stage I grade I patients and 63% for the remaining patients (p ⫽ 0.0107). 13 patients (34%) received a dose of 3000 cGy, all with stage I disease. Four of these patients had grade III while the rest had grade I disease. The actuarial 15 year DSS in this group was 100% versus 71% for patients with less than 3000 cGy. No complications were encountered during HDRB. Acute toxicities were limited to grade I-II that occurred in three patients (8%). Four patients experienced late toxicities, one grade II (3%) and 3 (8%) grade III and IV. Conclusions: Medically inoperable stage I endometrial carcinoma may be safely treated with HDRB as the primary treatment. In selected stage I patients our results are equivalent to that of surgery. We believe that the alternative option of HDRB as the primary treatment for selected stage I endometrial carcinoma, even in patients with low operative risks, needs further evaluation.
1085
Radiation Therapy in the Treatment of Advanced Endometrial Carcinoma
J. T. Payne, J. Yoneda, M. Mohiuddin, A. Meigooni, U. Malik Department of Radiation Medicine, University of Kentucky, Lexington, KY Purpose/Objective: The treatment of stage I and II endometrial carcinoma with external beam radiotherapy with or without brachytherapy boost resulting in a local recurrence rate of approximately 4% has been well established. Studies looking at recurrence in high risk endometrial cancer have concentrated on reducing distant failure with whole abdominal radiotherapy. However there remains a large percentage of patients with advanced disease who fail locally. The goal of this retrospective study was to determine differences in the local failure rate in patients with early and high risk endometrial cancer. Materials/Methods: Between January 1996 and February 2003, 101 patients with FIGO stage IB through IIIC endometrial cancer treated with radiotherapy were evaluated. Patients with endometrial adenocarcinoma with papillary serous, clear cell or MMMT histology were excluded from the analysis. Patients who were initially treated for recurrent endometrial cancer were also excluded. This resulted in 31 evaluable patients of which 24 had FIGO stage I and II disease and 7 had FIGO stage III disease. The group of patients with FIGO stage III disease consisted of one stage IIIA, one stage IIIB, and 5 stage IIIC patients.
S307
S308
I. J. Radiation Oncology
● Biology ● Physics
Volume 60, Number 1, Supplement, 2004
These patients were treated with doses of external beam radiotherapy to the whole pelvis ranging from 4500 to 4560 cGy. Total doses to affected lymph nodes ranged from 4500 to 7020 cGy. Brachytherapy boosts were given in all cases and ranged from 700 to 2100 cGy (mean 1412 cGy) Follow-up for all patients ranged from 13 to 90 months. Results: In the group of patients with FIGO stage I and II disease, one patient developed local recurrence (4%) and a second developed distant disease (4%). In the group of seven patients with high risk disease (FIGO stage III), there were three failures (43%). One patient died of metastatic disease, one developed local (vaginal apex) recurrence and later distant disease and the third was found to have vaginal apical recurrence and lymph node involvement. The vaginal apical recurrence rate in the high risk group was 2 of 7 patients (29%). The difference in vaginal apex recurrence between the FIGO stage I, II group and the stage III group approached significance with a p value of 0.055. Conclusions: The differences in vaginal apex recurrence between the FIGO stage I, II group and the FIGO stage III group suggest that radiation doses to the vaginal apex may need to be escalated via brachytherapy to improve local control for high risk endometrial cancer patients.
1086
Combination High-Dose-Rate Brachytherapy and External Beam Radiation Therapy for the Treatment of Primary Vaginal Cancer: 5-Year Results
Y. E. Lieskovsky,1 D. Demanes2 Radiation Oncology, Stanford University, Stanford, CA,
1
2
, California Endocurietherapy Cancer Center, Oakland, CA
Purpose/Objective: To report the outcome of high-dose-rate (HDR) brachytherapy and external beam radiation therapy (EBRT) for vaginal carcinoma. Materials/Methods: A total of 54 patients received HDR brachytherapy for primary vaginal carcinoma between September 1991 and December 2001 were analyzed. FIGO stages I-IV were found in 6, 41, 6, and 1 patients, respectively. Histology was adenocarcinoma, adenosquamous carcinoma, and squamous cell carcinoma in 11, 1, and 42 patients. EBRT was delivered to 52 patients; it consisted of 36 Gy to the pelvis and 50.4 Gy to the pelvic sidewalls with a midline block introduced at 36 Gy, cut to match the 100% brachytherapy isodose line. Eight patients with lower vaginal lesions received 50.4 Gy EBRT to bilateral inguinal nodes. HDR brachytherapy was administered in 6 fractions 5.5 Gy to a total dose of 33 Gy. Early stages of disease (Stages I-II) were treated with 6 intracavitary HDR applications (twice a week for 3 weeks) alone (n ⫽ 1) or combined with external beam therapy (n ⫽ 9), whereas more advanced diseases (Stages II-IV) was treated with interstitial HDR brachytherapy (two implants a week apart with 3 fractions per implant) alone (n ⫽ 1) or combined with EBRT (n ⫽ 44). Eight patients received chemotherapy with Cisplatinum and 5-FU. Results: Mean follow-up was 45 months. Local control rate was 87% (7/54), pelvic control rate was 85% (9/54), distant metastatisis rate was 15% (8/54). Five-year overall survival rate for all patients was 52% and disease-free survival was 69%. Of the 14 patients who died of disease, 6 had pelvic failure only, 5 had distant failure only, and 3 had pelvic and distant failure. There was a 7% incidence of Grade 3 RTOG late gynecologic morbidity (4 cases of vaginal necrosis that resolved completely with hyperbaric oxygen treatment). There was a 7% incidence of Grade 4 GI/GU morbidity (1 case of a vesico-vaginal fistula, 2 cases of recto-vaginal fistula, and 1 case of small bowel obstruction requiring permanent ileostomy). Conclusions: HDR brachytherapy is an effective and well-tolerated treatment for cancer of the vagina that results in preservation of bowel and bladder function in most cases.
1087
Risk Factors Associated with Incomplete Brainstem Recovery Following Post-Operative Conformal Radiation Therapy for Infratentorial Ependymoma
R. M. Chitti,1 R. B. Khan,1 X. Xiong,2 T. E. Merchant1 Radiological Sciences, St. Jude Children’s Research Hospital, Memphis, TN, 2Biostatistics, St. Jude Children’s Research Hospital, Memphis, TN 1
Purpose/Objective: Identify risk factors associated with incomplete brainstem recovery in pediatric patients with infratentorial ependymoma who received post operative conformal radiation therapy (54 –59.4Gy) and determine the effect of radiation dose on brainstem function. Materials/Methods: The study group included 66 patients (median age 2.6yrs ⫾ 3.8yrs) followed more than 6 months post irradiation (median 36 months, range 7–76 months) and assessed for brainstem function by neurological examination of cranial nerves V-VII and IX-XII, motor weakness and dysmetria. Patients were divided into three groups representing normal baseline and follow-up (NL, n ⫽ 17), abnormal baseline and full recovery at last follow-up (FR, n ⫽ 13), abnormal baseline with partial recovery at last follow-up (PR, n ⫽ 35), and progressive deficits (PD, n ⫽ 1). Patient grouping was correlated with clinical and treatment related factors including age at time of irradiation, extent and number of surgical procedures, hydrocephalus, CSF shunting, number of CSF shunting procedures, gross tumor volume (GTV), planning target volume (PTV), mean brainstem dose and the percent volume of the brainstem receiving ⱖ54Gy. Patients were treated with conformal radiation therapy using an anatomically-confined clinical target volume (CTV) margin of 10mm surrounding the post-operatively defined gross tumor volume and a geometrically-expanded PTV of 3–5mm surrounding the CTV. The 100% isodose volume (⫺5%/⫹10%) encompassed the PTV. The mean brainstem dose was 54.88Gy (⫾ 4.65 Gy). Results: Risk factors associated with partial recovery included more than one surgical resection (NL 1/17 vs. FR 3/13 vs. PR 18/35, p ⫽ 0.0006), CSF shunting (NL2/17 vs. FR 2/13 vs. PR 20/35, p ⫽ 0.0004), number of CSF shunting procedures including revisions (NL 2/17 vs. FR 2/13 vs. PR 20/35; p ⫽ 0.0004), and total number of surgical resection and shunting procedures (NL⫹FR 8/30 vs. PR 24/35; p ⫽ 0.0011). Separate analysis including only patients under the age of 3 years and grouped according to NL⫹FR (n ⫽ 16) and PR (n ⫽ 25) showed more than one surgical resection (NL⫹FR 1/16 vs. PR 12/24, p ⫽ 0.0053), CSF shunting (NL⫹FR 1/16 vs. PR 14/24; p ⫽ 0.0021) , and total number of surgical resection and shunting procedures (NL ⫹ FR 2/16 vs. PR 15/24 p ⫽ 0.0028) to be associated with partial recovery. There was a statistically significant