International Journal of Radiation Oncology*Biology*Physics, 2015
Magnetic resonance imaging (MRI)-guided brachytherapy is a developing treatment modality for cerv... more Magnetic resonance imaging (MRI)-guided brachytherapy is a developing treatment modality for cervical cancer because its inherent benefits are 3D volume-based brachytherapy planning and MRI target delineation. A large institutional review of patients treated with MRIguided brachytherapy for cervical cancer was conducted, revealing high rates of local control at 2 years, with limited late toxicities. A dose-response relationship was seen for Purpose: Image-based brachytherapy is increasingly used for gynecologic malignancies. We report early outcomes of magnetic resonance imaging (MRI)-guided brachytherapy. Methods and Materials: Consecutive patient cases with FIGO stage IB1 to IVA cervical cancer treated at a single institution were retrospectively reviewed. All patients received concurrent cisplatin with external beam radiation therapy along with interdigitated highedose-rate intracavitary brachytherapy. Computed tomography or MRI was completed after each application, the latter acquired for at least 1 fraction. High-risk clinical target volume (HRCTV) and organs at risk were identified by Groupe Européen de Curiethérapie and European SocieTy for Radiotherapy and Oncology guidelines. Doses were converted to equivalent 2-Gy doses (EQD 2 ) with planned HRCTV doses of 75 to 85 Gy. Results: From 2007 to 2013, 128 patients, median 52 years of age, were treated. Predominant characteristics included stage IIB disease (58.6%) with a median tumor size of 5 cm, squamous histology (82.8%), and no radiographic nodal involvement (53.1%). Most patients (67.2%) received intensity modulated radiation therapy (IMRT) at a median dose of 45 Gy, followed by a median brachytherapy dose of 27.5 Gy (range, 25-30 Gy) in 5 fractions. At a median follow up of 24.4 months (range, 2.1-77.2 months), estimated 2-year local control, disease-free survival, and
Data for salvage radiotherapy for recurrent endometrial cancer are limited especially in the era ... more Data for salvage radiotherapy for recurrent endometrial cancer are limited especially in the era of modern radiotherapy including IMRT and 3-dimensional image-based HDR brachytherapy. Theoretically, modern radiotherapy reduces the dose to critical organs-at-risk and maximizes dose to the target volume, possibly decreasing morbidity and increasing tumor control. Forty-one patients completing definitive salvage radiotherapy for vaginal recurrence of endometrial cancer from June 2004 to December 2013 were retrospectively reviewed. HDR Brachytherapy was completed using image-based planning with contouring/optimization with each fraction to a median dose of 23.75 Gy in 5 fractions. HDR brachytherapy was preceded by external beam radiotherapy predominately using an IMRT technique (90%) to a median dose of 45 Gy in 25 fractions. Toxicity was reported according to CTCAEv4. At a median follow-up of 18 months (range: 3-78), the clinical complete response rate was 95%. The 3-year local control, distant control, recurrence free survival, and overall survival were 95%, 61%, 68%, and 67%. Significant predictors of both distant failure and overall survival were primary prognostic factors of depth of myometrial invasion, FIGO stage, and FIGO grade. There was no grade 3+ acute toxicity; the 3-year rate of grade 3+ late toxicity was 8%. Salvage IMRT plus 3-dimensional image-based HDR brachytherapy shows excellent tumor control and minimal morbidity for vaginal recurrence of endometrial cancer. Anticipated salvage rates must be taken in the context of primary risk factors including depth of myometrial invasion, FIGO stage, and FIGO grade.
... Int J Radiat Oncol Biol Phys 44:855-866 Park W,Huh SJ et al.(2005) Variation of small bowel s... more ... Int J Radiat Oncol Biol Phys 44:855-866 Park W,Huh SJ et al.(2005) Variation of small bowel sparing with small ... Author: Hayeon Kim Institute: Radiation Oncology in Magee Womens Hospital of University of Pittsburgh Cancer Institute Street: 300 Halket Street City: Pittsburgh, PA ...
To investigate the treatment effects and toxicities of extended-field intensity modulated radiati... more To investigate the treatment effects and toxicities of extended-field intensity modulated radiation therapy (EF-IMRT) and intra-cavitary brachytherapy combined with chemotherapy for stageIb1-IVa cervical cancer with positive para-aortic lymph nodes. A total of 46 stage Ib1-IVa cervical cancer patients with positive para-aortic lymph nodes treated at Fudan University Shanghai Cancer Center between 2009 and 2011 were reviewed. Neoadjuvant, concomitant and adjuvant chemotherapy with paclitaxel and carboplatin were administrated for one cycle before radiation therapy, two cycles during radiation therapy or three cycles after radiation therapy. All patients received EF-IMRT and intra-cavitary brachytherapy. The positive lymph nodes received an additional boost dose. All patients received EF-IMRT to 50.4 Gy (1.8 Gy per fraction). Twenty-six patients was treated with boost dose of 6.0-8.0 Gy in 2.0 Gy per fraction to positive para-aortic lymph nodes. Thirty-seven patients received a positive para-aortic lymph nodes boost or (and) parametrial boost. All patient also received a high-dose-rate intra-cavitary brachytherapy at the point "A" dose of 20.0-30.0 Gy in 5.0 Gy per fraction. Total chemotherapy cycles were 189, and the average patient received 4.1 courses. Two cases (4%, 2/46) experienced grade III gastrointestinal toxicities, no patients suffered grade IV gastrointestinal toxicities. Fifteen cases (33%, 15/46) experienced grade III hematological toxicities, and 3(7%, 3/46) experienced grade IV hematological toxicities.Late grade III-IV toxicity was seen in 3 cases (7%, 3/46). The 3 year progression- free survival rate was 46.2%, and the 3 years overall survival rate was 61.2%. EF-IMRT and intra-cavitary brachytherapy combined with chemotherapy is safe and effective for stageIb1-IVa cervical cancer with positive para-aortic lymph nodes.
PurposeThe study aimed to assess the outcome of locally advanced cervical and vaginal cancer trea... more PurposeThe study aimed to assess the outcome of locally advanced cervical and vaginal cancer treated with high-dose-rate interstitial brachytherapy (HDRB).
Purpose: For patients undergoing external beam radiation therapy (EBRT) and brachytherapy, recomm... more Purpose: For patients undergoing external beam radiation therapy (EBRT) and brachytherapy, recommendations for target doses and constraints are based on calculation of the equivalent dose in 2 Gy fractions (EQD2) from each phase. At present, the EBRT dose distribution is assumed to be uniform throughout the pelvis. We performed a preliminary study to determine whether deformable dose distribution mapping from the EBRT onto magnetic resonance (MR) images for the brachytherapy would yield differences in doses for organs at risk (OARs) and high-risk clinical target volume (HR-CTV).
PurposeTo evaluate dosimetric and clinical outcomes of three-dimensional (3D) image–based high-do... more PurposeTo evaluate dosimetric and clinical outcomes of three-dimensional (3D) image–based high-dose-rate (HDR) interstitial brachytherapy (HDRB) in patients with vaginal cancers.
To investigate the clinical feasibility and treatment outcomes of image-based high-dose-rate (HDR... more To investigate the clinical feasibility and treatment outcomes of image-based high-dose-rate (HDR) brachytherapy using an intracavitary multichannel vaginal cylinder for the definitive treatment of vaginal cancers. A total of 41 patients with vaginal cancer (24% primary vaginal and 76% recurrence from other gynecologic primaries) treated with definitive radiotherapy ± chemotherapy including image-based HDR brachytherapy with a multichannel vaginal cylinder were included in the study. Image-based brachytherapy was completed using either CT- (41%) or MR-based planning (59%) with each fraction. The high-risk clinical target volume was defined based on the pre- and postexternal beam radiotherapy gross tumor volume. Doses were converted to equivalent dose of 2Gy per fraction. Endpoints examined were dose-volume parameters and early clinical outcomes. The median high-risk clinical target volume was 24.2 cc (interquartile range [IQR], 12.6), with a median dose to 90% (D90) of 77.1 Gy (IQR, 3.4). The median dose to 2 cc (D(2 cc)) for the bladder, rectum, and sigmoid were 59.4 Gy (IQR, 5.6), 58.2 Gy (IQR, 4.1), and 52.3 Gy (IQR, 5.5), respectively. After a median followup of 16 months (range, 3-35), complete clinical response was documented in 98% of the patients. The 2-year local, regional, and distant control; and disease-free and overall survival were 93%, 100%, 81%, 78%, and 88%, respectively. The 2-year actuarial rate of late Grade 3 or higher toxicity was 4% overall with 0%, 0%, 0%, and 4% for vaginal, bladder, urethral, and gastrointestinal, respectively. Image-based HDR brachytherapy using an intracavitary multichannel cylinder seems feasible in definitive vaginal cancer treatment. The described clinical implementation shows promising early clinical outcomes with high rates of local control and little toxicity, which should be validated with extended followup.
For locally-advanced uterine cancer clinically extending to the cervix, two treatment paradigms e... more For locally-advanced uterine cancer clinically extending to the cervix, two treatment paradigms exist: surgical staging radical hysterectomy with tailored adjuvant therapy or neoadjuvant therapy followed by a less extensive simple hysterectomy. Currently, insufficient data exists to guide consensus guidelines and practical application of preoperative radiotherapy. Retrospective IRB approved cohort study from 1999 to 2014 of 36 endometrial cancer patients with clinical involvement of cervix±parametria treated with neoadjuvant external beam radiotherapy (45-50.4Gy in 25-28 fractions) and image-based HDR brachytherapy (5-5.5Gy times 3-4 fractions)±chemotherapy followed by extrafascial hysterectomy performed at a median of 6weeks after radiotherapy. All patients had clinical cervical extension, 50% also had parametria extension, and 31% had nodal involvement. At the time of surgery 91% had no clinical cervical involvement, 58% had no pathologic cervical involvement, and all had margin negative resection. The pathologic complete response rate was 24%. Median follow-up from the time of surgery was 20months (range: 0-153). The 3-year local control, regional control, distant control, disease free survival and overall survival rates were 96%, 89%, 84%, 73%, and 100%. The 3-year rate of grade 3 complications was 11%, with no grade 4+ toxicity. Neoadjuvant radiation therapy±chemotherapy followed by extrafascial hysterectomy appears to be a viable option for patients with endometrial cancer clinically extending to the cervix and parametria. The HDR brachytherapy schema of 5-5.5Gy times 3-4 fractions, for a cumulative EQD2 of 60-70Gy, is well tolerated with high rates of clinical and pathological response.
International Journal of Radiation Oncology*Biology*Physics, 2014
Positron emission tomography/computed tomography (PET/CT) is commonly used for nodal staging in l... more Positron emission tomography/computed tomography (PET/CT) is commonly used for nodal staging in locally advanced cervical cancer; however the false negative rate for para-aortic disease are 20% to 25% in PET-positive pelvic nodal disease. Unless surgically staged, pelvis-only treatment may undertreat para-aortic disease. We have treated patients with PET-positive nodes with extended field intensity modulated radiation therapy (IMRT) to address the para-aortic region prophylactically with concomitant boost to involved nodes. The purpose of this study was to assess regional control rates and recurrence patterns. Sixty-one patients with cervical cancer (stage IBI-IVA) diagnosed from 2003 to 2012 with PET-avid pelvic nodes treated with extended field IMRT (45 Gy in 25 fractions with concomitant boost to involved nodes to a median of 55 Gy in 25 fractions) with concurrent cisplatin and brachytherapy were retrospectively analyzed. The nodal location was pelvis-only in 41 patients (67%) and pelvis + para-aortic in 20 patients (33%). There were a total of 179 nodes, with a median number of positive nodes of 2 (range, 1-16 nodes) per patient and a median nodal size of 1.8 cm (range, 0.7-4.5 cm). Response was assessed by PET/CT at 12 to 16 weeks. Complete clinical and imaging response at the first follow-up visit was seen in 77% of patients. At a mean follow-up time of 29 months (range, 3-116 months), 8 patients experienced recurrence. The sites of persistent/recurrent disease were as follows: cervix 10 (16.3%), regional nodes 3 (4.9%), and distant 14 (23%). The rate of para-aortic failure in patients with pelvic-only nodes was 2.5%. There were no significant differences in recurrence patterns by the number/location of nodes, largest node size, or maximum node standardized uptake value. The rate of late grade 3+ adverse events was 4%. Extended field IMRT was well tolerated and resulted in low regional recurrence in node-positive cervical cancer. The dose of 55 Gy in 25 fractions was effective in eradicating disease in involved nodes, with acceptable late adverse events. Distant metastasis is the predominant mode of failure, and the OUTBACK trial may challenge the presented paradigms.
Definitive radiotherapy is a viable option for medically inoperable patients with early stage end... more Definitive radiotherapy is a viable option for medically inoperable patients with early stage endometrial cancer. We present our experience using image-based brachytherapy (BT). Patients with medically inoperable clinical Stage I endometrial adenocarcinoma received definitive BT with or without external beam radiotherapy. High-dose-rate BT was delivered using MRI- or CT-based planning for each fraction. For patients with an MRI, gross tumor volume (GTV) was contoured although dose was still prescribed to the clinical treatment volume (CTV), including the entire uterus, cervix, and upper 1-2 cm of vagina. Equivalent 2 Gy doses (EQD2) were calculated. Thirty-eight patients were treated from 2007 to 2013, 20 receiving BT alone with a median dose of 37.5 Gy in five to six fractions. For combined therapy, median external beam and BT doses were 45 and 25 Gy in four to five fractions. With 15-month median followup, the 2-year actuarial local control and overall survival were 90.6% and 94.4%. No Grade 2-5 late toxicities were observed. Mean CTV D90 EQD2 for BT alone and combined therapy was 48.6 ± 5.6 and 72.4 ± 6.0 Gy, whereas mean GTV D90 EQD2 was 172.3 ± 59.6 and 138.0 ± 64.6 Gy. Image-based BT is feasible for medically inoperable early stage endometrial cancer with excellent early results. Despite low CTV doses, high doses delivered to GTV with BT likely accounts for high local control. Endometrial cancer guidelines for image-based planning are needed to define target volumes based on risk with differential dose delivery.
Objective.To assess local control and chronic toxicity with IMRT for adjuvant treatment of endome... more Objective.To assess local control and chronic toxicity with IMRT for adjuvant treatment of endometrial carcinoma.
The purpose of this study was to analyze the dosimetric outcome of 3D image-guided high-dose-rate... more The purpose of this study was to analyze the dosimetric outcome of 3D image-guided high-dose-rate (HDR) brachytherapy planning for cervical cancer treatment and compare dose coverage of high-risk clinical target volume (HRCTV) to traditional Point A dose. Thirty-two patients with stage IA2-IIIB cervical cancer were treated using computed tomography/magnetic resonance imaging-based image-guided HDR brachytherapy (IGBT). Brachytherapy dose prescription was 5.0-6.0 Gy per fraction for a total 5 fractions. The HRCTV and organs at risk (OARs) were delineated following the GYN GEC/ESTRO guidelines. Total doses for HRCTV, OARs, Point A, and Point T from external beam radiotherapy and brachytherapy were summated and normalized to a biologically equivalent dose of 2 Gy per fraction (EQD2). The total planned D90 for HRCTV was 80-85 Gy, whereas the dose to 2 mL of bladder, rectum, and sigmoid was limited to 85 Gy, 75 Gy, and 75 Gy, respectively. The mean D90 and its standard deviation for HRCTV was 83.2 ± 4.3 Gy. This is significantly higher (p < 0.0001) than the mean value of the dose to Point A (78.6 ± 4.4 Gy). The dose levels of the OARs were within acceptable limits for most patients. The mean dose to 2 mL of bladder was 78.0 ± 6.2 Gy, whereas the mean dose to rectum and sigmoid were 57.2 ± 4.4 Gy and 66.9 ± 6.1 Gy, respectively. Image-based 3D brachytherapy provides adequate dose coverage to HRCTV, with acceptable dose to OARs in most patients. Dose to Point A was found to be significantly lower than the D90 for HRCTV calculated using the image-based technique. Paradigm shift from 2D point dose dosimetry to IGBT in HDR cervical cancer treatment needs advanced concept of evaluation in dosimetry with clinical outcome data about whether this approach improves local control and/or decreases toxicities.
International Journal of Radiation Oncology*Biology*Physics, 2014
Accelerated partial breast irradiation (APBI) with balloon and catheter-based brachytherapy has g... more Accelerated partial breast irradiation (APBI) with balloon and catheter-based brachytherapy has gained increasing popularity in recent years and is the subject of ongoing phase III trials. Initial data suggest promising local control and cosmetic results in appropriately selected patients. Long-term data continue to evolve but are limited outside of the context of the American Society of Breast Surgeons Registry Trial. A retrospective review of 157 patients completing APBI after breast-conserving surgery and axillary staging via high-dose-rate (192)Ir brachytherapy from June 2002 to December 2007 was made. APBI was delivered with a single-lumen MammoSite balloon-based applicator to a median dose of 34 Gy in 10 fractions over a 5-day period. Tumor coverage and critical organ dosimetry were retrospectively collected on the basis of computed tomography completed for conformance and symmetry. At a median follow-up time of 5.5 years (range, 0-10.0 years), the 5-year and 7-year actuarial incidences of ipsilateral breast control were 98%/98%, of nodal control 99%/98%, and of distant control 99%/99%, respectively. The crude rate of ipsilateral breast recurrence was 2.5% (n=4); of nodal failure, 1.9% (n=3); and of distant failure, 0.6% (n=1). The 5-year and 7-year actuarial overall survival rates were 89%/86%, with breast cancer-specific survival of 100%/99%, respectively. Good to excellent cosmetic outcomes were achieved in 93.4% of patients. Telangiectasia developed in 27% of patients, with 1-year, 3-year, and 5-year actuarial incidence of 7%/24%/33%; skin dose >100% significantly predicted for the development of telangiectasia (50% vs 14%, P<.0001). Long-term single-institution outcomes suggest excellent tumor control, breast cosmesis, and minimal late toxicity. Skin toxicity is a function of skin dose, which may be ameliorated with dosimetric optimization afforded by newer multicatheter brachytherapy applicators and a more rigorous skin dose constraint of ≤100%.
International Journal of Radiation Oncology*Biology*Physics, 2007
Purpose: To determine the dosimetric and toxicity differences between prone and supine position i... more Purpose: To determine the dosimetric and toxicity differences between prone and supine position intensitymodulate radiotherapy in endometrial cancer patients treated with adjuvant radiotherapy. Methods: Forty-seven consecutive endometrial cancer patients treated with adjuvant RT were analyzed. Of these, 21 were treated in prone position and 26 in the supine position. Dose-volume histograms for normal tissue structures and targets were compared between the two groups. Acute and chronic toxicity were also compared between the cohorts. Results: The percentage of volume receiving 10, 20, 30, 40, 45, and 50 Gy for small bowel was 89.5%, 69%, 33%, 12.2%, 5%, and 0% in the prone group and 87.5%, 62.7%, 26.4%, 8%, 4.3%, and 0% in the supine group, respectively. The difference was not statistically significant. The dose-volume histograms for bladder and rectum were also comparable, except for a slightly greater percentage of volume receiving 10 Gy (1.5%) and 20 Gy (5%) for the rectum in the prone group. Acute small bowel toxicities were Grade 1 in 7 patients and Grade 2 in 14 patients in the prone group vs. Grade 1 in 6 patients and Grade 2 in 19 patients in the supine group. Chronic toxicity was Grade 1 in 7 patients and Grade 3 in 1 patient in the prone group and Grade 1 in 5 patients in the supine group. Conclusion: These preliminary results suggest that no difference exists in the dose to the normal tissue and toxicity between prone and supine intensity-modulated radiotherapy for endometrial cancer. Longer follow-up and more outcome studies are needed to determine whether any differences exist between the two approaches.
International Journal of Radiation Oncology*Biology*Physics, 2007
To assess the early clinical outcomes with concurrent Cisplatin and extended-field radiotherapy (... more To assess the early clinical outcomes with concurrent Cisplatin and extended-field radiotherapy (EFRT) using intensity-modulated radiotherapy technique (IMRT) for carcinoma of the cervix. Materials/Methods: Thirty-six patients with cervical cancer stages 1B2-IVA treated with EFRT using IMRT technique were evaluated for this study. Nineteen of these patients had pelvic nodal involvement. Of the 19 patients, 10 also had para-aortic lymph node involvement. The nodes were detected on PET/CT in 9 patients and on CT/MRI scans in 10 patients. The treatment volume included the cervix, uterus, parametria, presacral space, upper vagina, pelvic, common iliac, and para-aortic nodes to the superior border of L1. All regions received 45 Gy in 25 fractions. A simultaneous or sequential boost was delivered to involved nodes (55-60 Gy in 25-30 fractions). Cisplatin was delivered weekly at a dose of 40 mg/m2. Patients were assessed for acute and late treatment-related toxicities using the NCI's CTCAE, v3.0. Response was evaluated both clinically and radiographically. Results: All patients completed the prescribed course of EFRT. All but 2 patients recieved brachytherapy. Median length of treatment was 53 days (range 36 -83). Treatment breaks for a median of 9 days (range 2-16 days) were required in 5 patients because of myelotoxicity. Three patients had their last chemotherapy cycle held because of myelotoxicity. The median follow-up for surviving patients was 18 months (5-48 months). Acute Grade 3 GI, GU and myelotoxicity was seen in 1, 1 and 10 patients, respectively. Only, one patient had late grade 3 GI toxicity. Thirty-three patients had complete response to treatment. Of these 33 patients, 11 patients (33%) developed recurrences -2 local (6%), 8 distant (24%) and 1 suburethral (3%). No patient had isolated para-aortic recurrence. Of the 19 patients with positive lymph nodes, 7 (37%) developed systemic recurrence. The 2-year actuarial pelvic control, disease-free survival and overall survival were 78%, 51% and 54%, respectively. Conclusions: EFRT using IMRT with concurrent chemotherapy was tolerated well with acceptable acute and early late toxicities. The pelvic and para-aortic control rate was good with distant metastases being the predominant site of failure in patients with nodal disease. We continue to accrue more patients and longer follow-ups in order to further extend our initial observations.
International Journal of Radiation Oncology*Biology*Physics, 2006
To assess early clinical outcome of intensity-modulated radiation therapy (IMRT) in the treatment... more To assess early clinical outcome of intensity-modulated radiation therapy (IMRT) in the treatment of vulvar cancer and compare dosimetric parameters with 3D conformal radiotherapy (3D CRT). Fifteen patients with vulvar cancer were treated with IMRT. Seven patients were treated with preoperative chemoradiation, and 8 patients were treated with adjuvant postoperative radiation therapy. Median dose was 46 Gy in the preoperative and 50.4 Gy in the postoperative group. The mean volume of small bowel, rectum, and bladder that received doses in excess of 30 Gy with IMRT was reduced when compared with 3D CRT. Treatment was well tolerated, and only 1 patient had acute Grade 3 small-bowel toxicity. Median follow-up was 12 months. In the preoperative group, 5 patients (71%) had clinical complete response and 3 patients (42.8%) had pathologic complete response. In the adjuvant group, 2 patients had recurrences in the treatment field. No patients had late Grade 3 toxicity. The 2-year actuarial disease-specific survival was 100%. Intensity-modulated RT appears to offer advantages over 3D CRT treatment of vulvar cancer by elimination of dose modulation across overlapping regions and reduction of unnecessary dose to the bladder, rectum, and small bowel. Early results with a small number of patients show promising results, with a low incidence of severe toxicity.
International Journal of Radiation Oncology*Biology*Physics, 2015
Magnetic resonance imaging (MRI)-guided brachytherapy is a developing treatment modality for cerv... more Magnetic resonance imaging (MRI)-guided brachytherapy is a developing treatment modality for cervical cancer because its inherent benefits are 3D volume-based brachytherapy planning and MRI target delineation. A large institutional review of patients treated with MRIguided brachytherapy for cervical cancer was conducted, revealing high rates of local control at 2 years, with limited late toxicities. A dose-response relationship was seen for Purpose: Image-based brachytherapy is increasingly used for gynecologic malignancies. We report early outcomes of magnetic resonance imaging (MRI)-guided brachytherapy. Methods and Materials: Consecutive patient cases with FIGO stage IB1 to IVA cervical cancer treated at a single institution were retrospectively reviewed. All patients received concurrent cisplatin with external beam radiation therapy along with interdigitated highedose-rate intracavitary brachytherapy. Computed tomography or MRI was completed after each application, the latter acquired for at least 1 fraction. High-risk clinical target volume (HRCTV) and organs at risk were identified by Groupe Européen de Curiethérapie and European SocieTy for Radiotherapy and Oncology guidelines. Doses were converted to equivalent 2-Gy doses (EQD 2 ) with planned HRCTV doses of 75 to 85 Gy. Results: From 2007 to 2013, 128 patients, median 52 years of age, were treated. Predominant characteristics included stage IIB disease (58.6%) with a median tumor size of 5 cm, squamous histology (82.8%), and no radiographic nodal involvement (53.1%). Most patients (67.2%) received intensity modulated radiation therapy (IMRT) at a median dose of 45 Gy, followed by a median brachytherapy dose of 27.5 Gy (range, 25-30 Gy) in 5 fractions. At a median follow up of 24.4 months (range, 2.1-77.2 months), estimated 2-year local control, disease-free survival, and
Data for salvage radiotherapy for recurrent endometrial cancer are limited especially in the era ... more Data for salvage radiotherapy for recurrent endometrial cancer are limited especially in the era of modern radiotherapy including IMRT and 3-dimensional image-based HDR brachytherapy. Theoretically, modern radiotherapy reduces the dose to critical organs-at-risk and maximizes dose to the target volume, possibly decreasing morbidity and increasing tumor control. Forty-one patients completing definitive salvage radiotherapy for vaginal recurrence of endometrial cancer from June 2004 to December 2013 were retrospectively reviewed. HDR Brachytherapy was completed using image-based planning with contouring/optimization with each fraction to a median dose of 23.75 Gy in 5 fractions. HDR brachytherapy was preceded by external beam radiotherapy predominately using an IMRT technique (90%) to a median dose of 45 Gy in 25 fractions. Toxicity was reported according to CTCAEv4. At a median follow-up of 18 months (range: 3-78), the clinical complete response rate was 95%. The 3-year local control, distant control, recurrence free survival, and overall survival were 95%, 61%, 68%, and 67%. Significant predictors of both distant failure and overall survival were primary prognostic factors of depth of myometrial invasion, FIGO stage, and FIGO grade. There was no grade 3+ acute toxicity; the 3-year rate of grade 3+ late toxicity was 8%. Salvage IMRT plus 3-dimensional image-based HDR brachytherapy shows excellent tumor control and minimal morbidity for vaginal recurrence of endometrial cancer. Anticipated salvage rates must be taken in the context of primary risk factors including depth of myometrial invasion, FIGO stage, and FIGO grade.
... Int J Radiat Oncol Biol Phys 44:855-866 Park W,Huh SJ et al.(2005) Variation of small bowel s... more ... Int J Radiat Oncol Biol Phys 44:855-866 Park W,Huh SJ et al.(2005) Variation of small bowel sparing with small ... Author: Hayeon Kim Institute: Radiation Oncology in Magee Womens Hospital of University of Pittsburgh Cancer Institute Street: 300 Halket Street City: Pittsburgh, PA ...
To investigate the treatment effects and toxicities of extended-field intensity modulated radiati... more To investigate the treatment effects and toxicities of extended-field intensity modulated radiation therapy (EF-IMRT) and intra-cavitary brachytherapy combined with chemotherapy for stageIb1-IVa cervical cancer with positive para-aortic lymph nodes. A total of 46 stage Ib1-IVa cervical cancer patients with positive para-aortic lymph nodes treated at Fudan University Shanghai Cancer Center between 2009 and 2011 were reviewed. Neoadjuvant, concomitant and adjuvant chemotherapy with paclitaxel and carboplatin were administrated for one cycle before radiation therapy, two cycles during radiation therapy or three cycles after radiation therapy. All patients received EF-IMRT and intra-cavitary brachytherapy. The positive lymph nodes received an additional boost dose. All patients received EF-IMRT to 50.4 Gy (1.8 Gy per fraction). Twenty-six patients was treated with boost dose of 6.0-8.0 Gy in 2.0 Gy per fraction to positive para-aortic lymph nodes. Thirty-seven patients received a positive para-aortic lymph nodes boost or (and) parametrial boost. All patient also received a high-dose-rate intra-cavitary brachytherapy at the point "A" dose of 20.0-30.0 Gy in 5.0 Gy per fraction. Total chemotherapy cycles were 189, and the average patient received 4.1 courses. Two cases (4%, 2/46) experienced grade III gastrointestinal toxicities, no patients suffered grade IV gastrointestinal toxicities. Fifteen cases (33%, 15/46) experienced grade III hematological toxicities, and 3(7%, 3/46) experienced grade IV hematological toxicities.Late grade III-IV toxicity was seen in 3 cases (7%, 3/46). The 3 year progression- free survival rate was 46.2%, and the 3 years overall survival rate was 61.2%. EF-IMRT and intra-cavitary brachytherapy combined with chemotherapy is safe and effective for stageIb1-IVa cervical cancer with positive para-aortic lymph nodes.
PurposeThe study aimed to assess the outcome of locally advanced cervical and vaginal cancer trea... more PurposeThe study aimed to assess the outcome of locally advanced cervical and vaginal cancer treated with high-dose-rate interstitial brachytherapy (HDRB).
Purpose: For patients undergoing external beam radiation therapy (EBRT) and brachytherapy, recomm... more Purpose: For patients undergoing external beam radiation therapy (EBRT) and brachytherapy, recommendations for target doses and constraints are based on calculation of the equivalent dose in 2 Gy fractions (EQD2) from each phase. At present, the EBRT dose distribution is assumed to be uniform throughout the pelvis. We performed a preliminary study to determine whether deformable dose distribution mapping from the EBRT onto magnetic resonance (MR) images for the brachytherapy would yield differences in doses for organs at risk (OARs) and high-risk clinical target volume (HR-CTV).
PurposeTo evaluate dosimetric and clinical outcomes of three-dimensional (3D) image–based high-do... more PurposeTo evaluate dosimetric and clinical outcomes of three-dimensional (3D) image–based high-dose-rate (HDR) interstitial brachytherapy (HDRB) in patients with vaginal cancers.
To investigate the clinical feasibility and treatment outcomes of image-based high-dose-rate (HDR... more To investigate the clinical feasibility and treatment outcomes of image-based high-dose-rate (HDR) brachytherapy using an intracavitary multichannel vaginal cylinder for the definitive treatment of vaginal cancers. A total of 41 patients with vaginal cancer (24% primary vaginal and 76% recurrence from other gynecologic primaries) treated with definitive radiotherapy ± chemotherapy including image-based HDR brachytherapy with a multichannel vaginal cylinder were included in the study. Image-based brachytherapy was completed using either CT- (41%) or MR-based planning (59%) with each fraction. The high-risk clinical target volume was defined based on the pre- and postexternal beam radiotherapy gross tumor volume. Doses were converted to equivalent dose of 2Gy per fraction. Endpoints examined were dose-volume parameters and early clinical outcomes. The median high-risk clinical target volume was 24.2 cc (interquartile range [IQR], 12.6), with a median dose to 90% (D90) of 77.1 Gy (IQR, 3.4). The median dose to 2 cc (D(2 cc)) for the bladder, rectum, and sigmoid were 59.4 Gy (IQR, 5.6), 58.2 Gy (IQR, 4.1), and 52.3 Gy (IQR, 5.5), respectively. After a median followup of 16 months (range, 3-35), complete clinical response was documented in 98% of the patients. The 2-year local, regional, and distant control; and disease-free and overall survival were 93%, 100%, 81%, 78%, and 88%, respectively. The 2-year actuarial rate of late Grade 3 or higher toxicity was 4% overall with 0%, 0%, 0%, and 4% for vaginal, bladder, urethral, and gastrointestinal, respectively. Image-based HDR brachytherapy using an intracavitary multichannel cylinder seems feasible in definitive vaginal cancer treatment. The described clinical implementation shows promising early clinical outcomes with high rates of local control and little toxicity, which should be validated with extended followup.
For locally-advanced uterine cancer clinically extending to the cervix, two treatment paradigms e... more For locally-advanced uterine cancer clinically extending to the cervix, two treatment paradigms exist: surgical staging radical hysterectomy with tailored adjuvant therapy or neoadjuvant therapy followed by a less extensive simple hysterectomy. Currently, insufficient data exists to guide consensus guidelines and practical application of preoperative radiotherapy. Retrospective IRB approved cohort study from 1999 to 2014 of 36 endometrial cancer patients with clinical involvement of cervix±parametria treated with neoadjuvant external beam radiotherapy (45-50.4Gy in 25-28 fractions) and image-based HDR brachytherapy (5-5.5Gy times 3-4 fractions)±chemotherapy followed by extrafascial hysterectomy performed at a median of 6weeks after radiotherapy. All patients had clinical cervical extension, 50% also had parametria extension, and 31% had nodal involvement. At the time of surgery 91% had no clinical cervical involvement, 58% had no pathologic cervical involvement, and all had margin negative resection. The pathologic complete response rate was 24%. Median follow-up from the time of surgery was 20months (range: 0-153). The 3-year local control, regional control, distant control, disease free survival and overall survival rates were 96%, 89%, 84%, 73%, and 100%. The 3-year rate of grade 3 complications was 11%, with no grade 4+ toxicity. Neoadjuvant radiation therapy±chemotherapy followed by extrafascial hysterectomy appears to be a viable option for patients with endometrial cancer clinically extending to the cervix and parametria. The HDR brachytherapy schema of 5-5.5Gy times 3-4 fractions, for a cumulative EQD2 of 60-70Gy, is well tolerated with high rates of clinical and pathological response.
International Journal of Radiation Oncology*Biology*Physics, 2014
Positron emission tomography/computed tomography (PET/CT) is commonly used for nodal staging in l... more Positron emission tomography/computed tomography (PET/CT) is commonly used for nodal staging in locally advanced cervical cancer; however the false negative rate for para-aortic disease are 20% to 25% in PET-positive pelvic nodal disease. Unless surgically staged, pelvis-only treatment may undertreat para-aortic disease. We have treated patients with PET-positive nodes with extended field intensity modulated radiation therapy (IMRT) to address the para-aortic region prophylactically with concomitant boost to involved nodes. The purpose of this study was to assess regional control rates and recurrence patterns. Sixty-one patients with cervical cancer (stage IBI-IVA) diagnosed from 2003 to 2012 with PET-avid pelvic nodes treated with extended field IMRT (45 Gy in 25 fractions with concomitant boost to involved nodes to a median of 55 Gy in 25 fractions) with concurrent cisplatin and brachytherapy were retrospectively analyzed. The nodal location was pelvis-only in 41 patients (67%) and pelvis + para-aortic in 20 patients (33%). There were a total of 179 nodes, with a median number of positive nodes of 2 (range, 1-16 nodes) per patient and a median nodal size of 1.8 cm (range, 0.7-4.5 cm). Response was assessed by PET/CT at 12 to 16 weeks. Complete clinical and imaging response at the first follow-up visit was seen in 77% of patients. At a mean follow-up time of 29 months (range, 3-116 months), 8 patients experienced recurrence. The sites of persistent/recurrent disease were as follows: cervix 10 (16.3%), regional nodes 3 (4.9%), and distant 14 (23%). The rate of para-aortic failure in patients with pelvic-only nodes was 2.5%. There were no significant differences in recurrence patterns by the number/location of nodes, largest node size, or maximum node standardized uptake value. The rate of late grade 3+ adverse events was 4%. Extended field IMRT was well tolerated and resulted in low regional recurrence in node-positive cervical cancer. The dose of 55 Gy in 25 fractions was effective in eradicating disease in involved nodes, with acceptable late adverse events. Distant metastasis is the predominant mode of failure, and the OUTBACK trial may challenge the presented paradigms.
Definitive radiotherapy is a viable option for medically inoperable patients with early stage end... more Definitive radiotherapy is a viable option for medically inoperable patients with early stage endometrial cancer. We present our experience using image-based brachytherapy (BT). Patients with medically inoperable clinical Stage I endometrial adenocarcinoma received definitive BT with or without external beam radiotherapy. High-dose-rate BT was delivered using MRI- or CT-based planning for each fraction. For patients with an MRI, gross tumor volume (GTV) was contoured although dose was still prescribed to the clinical treatment volume (CTV), including the entire uterus, cervix, and upper 1-2 cm of vagina. Equivalent 2 Gy doses (EQD2) were calculated. Thirty-eight patients were treated from 2007 to 2013, 20 receiving BT alone with a median dose of 37.5 Gy in five to six fractions. For combined therapy, median external beam and BT doses were 45 and 25 Gy in four to five fractions. With 15-month median followup, the 2-year actuarial local control and overall survival were 90.6% and 94.4%. No Grade 2-5 late toxicities were observed. Mean CTV D90 EQD2 for BT alone and combined therapy was 48.6 ± 5.6 and 72.4 ± 6.0 Gy, whereas mean GTV D90 EQD2 was 172.3 ± 59.6 and 138.0 ± 64.6 Gy. Image-based BT is feasible for medically inoperable early stage endometrial cancer with excellent early results. Despite low CTV doses, high doses delivered to GTV with BT likely accounts for high local control. Endometrial cancer guidelines for image-based planning are needed to define target volumes based on risk with differential dose delivery.
Objective.To assess local control and chronic toxicity with IMRT for adjuvant treatment of endome... more Objective.To assess local control and chronic toxicity with IMRT for adjuvant treatment of endometrial carcinoma.
The purpose of this study was to analyze the dosimetric outcome of 3D image-guided high-dose-rate... more The purpose of this study was to analyze the dosimetric outcome of 3D image-guided high-dose-rate (HDR) brachytherapy planning for cervical cancer treatment and compare dose coverage of high-risk clinical target volume (HRCTV) to traditional Point A dose. Thirty-two patients with stage IA2-IIIB cervical cancer were treated using computed tomography/magnetic resonance imaging-based image-guided HDR brachytherapy (IGBT). Brachytherapy dose prescription was 5.0-6.0 Gy per fraction for a total 5 fractions. The HRCTV and organs at risk (OARs) were delineated following the GYN GEC/ESTRO guidelines. Total doses for HRCTV, OARs, Point A, and Point T from external beam radiotherapy and brachytherapy were summated and normalized to a biologically equivalent dose of 2 Gy per fraction (EQD2). The total planned D90 for HRCTV was 80-85 Gy, whereas the dose to 2 mL of bladder, rectum, and sigmoid was limited to 85 Gy, 75 Gy, and 75 Gy, respectively. The mean D90 and its standard deviation for HRCTV was 83.2 ± 4.3 Gy. This is significantly higher (p < 0.0001) than the mean value of the dose to Point A (78.6 ± 4.4 Gy). The dose levels of the OARs were within acceptable limits for most patients. The mean dose to 2 mL of bladder was 78.0 ± 6.2 Gy, whereas the mean dose to rectum and sigmoid were 57.2 ± 4.4 Gy and 66.9 ± 6.1 Gy, respectively. Image-based 3D brachytherapy provides adequate dose coverage to HRCTV, with acceptable dose to OARs in most patients. Dose to Point A was found to be significantly lower than the D90 for HRCTV calculated using the image-based technique. Paradigm shift from 2D point dose dosimetry to IGBT in HDR cervical cancer treatment needs advanced concept of evaluation in dosimetry with clinical outcome data about whether this approach improves local control and/or decreases toxicities.
International Journal of Radiation Oncology*Biology*Physics, 2014
Accelerated partial breast irradiation (APBI) with balloon and catheter-based brachytherapy has g... more Accelerated partial breast irradiation (APBI) with balloon and catheter-based brachytherapy has gained increasing popularity in recent years and is the subject of ongoing phase III trials. Initial data suggest promising local control and cosmetic results in appropriately selected patients. Long-term data continue to evolve but are limited outside of the context of the American Society of Breast Surgeons Registry Trial. A retrospective review of 157 patients completing APBI after breast-conserving surgery and axillary staging via high-dose-rate (192)Ir brachytherapy from June 2002 to December 2007 was made. APBI was delivered with a single-lumen MammoSite balloon-based applicator to a median dose of 34 Gy in 10 fractions over a 5-day period. Tumor coverage and critical organ dosimetry were retrospectively collected on the basis of computed tomography completed for conformance and symmetry. At a median follow-up time of 5.5 years (range, 0-10.0 years), the 5-year and 7-year actuarial incidences of ipsilateral breast control were 98%/98%, of nodal control 99%/98%, and of distant control 99%/99%, respectively. The crude rate of ipsilateral breast recurrence was 2.5% (n=4); of nodal failure, 1.9% (n=3); and of distant failure, 0.6% (n=1). The 5-year and 7-year actuarial overall survival rates were 89%/86%, with breast cancer-specific survival of 100%/99%, respectively. Good to excellent cosmetic outcomes were achieved in 93.4% of patients. Telangiectasia developed in 27% of patients, with 1-year, 3-year, and 5-year actuarial incidence of 7%/24%/33%; skin dose >100% significantly predicted for the development of telangiectasia (50% vs 14%, P<.0001). Long-term single-institution outcomes suggest excellent tumor control, breast cosmesis, and minimal late toxicity. Skin toxicity is a function of skin dose, which may be ameliorated with dosimetric optimization afforded by newer multicatheter brachytherapy applicators and a more rigorous skin dose constraint of ≤100%.
International Journal of Radiation Oncology*Biology*Physics, 2007
Purpose: To determine the dosimetric and toxicity differences between prone and supine position i... more Purpose: To determine the dosimetric and toxicity differences between prone and supine position intensitymodulate radiotherapy in endometrial cancer patients treated with adjuvant radiotherapy. Methods: Forty-seven consecutive endometrial cancer patients treated with adjuvant RT were analyzed. Of these, 21 were treated in prone position and 26 in the supine position. Dose-volume histograms for normal tissue structures and targets were compared between the two groups. Acute and chronic toxicity were also compared between the cohorts. Results: The percentage of volume receiving 10, 20, 30, 40, 45, and 50 Gy for small bowel was 89.5%, 69%, 33%, 12.2%, 5%, and 0% in the prone group and 87.5%, 62.7%, 26.4%, 8%, 4.3%, and 0% in the supine group, respectively. The difference was not statistically significant. The dose-volume histograms for bladder and rectum were also comparable, except for a slightly greater percentage of volume receiving 10 Gy (1.5%) and 20 Gy (5%) for the rectum in the prone group. Acute small bowel toxicities were Grade 1 in 7 patients and Grade 2 in 14 patients in the prone group vs. Grade 1 in 6 patients and Grade 2 in 19 patients in the supine group. Chronic toxicity was Grade 1 in 7 patients and Grade 3 in 1 patient in the prone group and Grade 1 in 5 patients in the supine group. Conclusion: These preliminary results suggest that no difference exists in the dose to the normal tissue and toxicity between prone and supine intensity-modulated radiotherapy for endometrial cancer. Longer follow-up and more outcome studies are needed to determine whether any differences exist between the two approaches.
International Journal of Radiation Oncology*Biology*Physics, 2007
To assess the early clinical outcomes with concurrent Cisplatin and extended-field radiotherapy (... more To assess the early clinical outcomes with concurrent Cisplatin and extended-field radiotherapy (EFRT) using intensity-modulated radiotherapy technique (IMRT) for carcinoma of the cervix. Materials/Methods: Thirty-six patients with cervical cancer stages 1B2-IVA treated with EFRT using IMRT technique were evaluated for this study. Nineteen of these patients had pelvic nodal involvement. Of the 19 patients, 10 also had para-aortic lymph node involvement. The nodes were detected on PET/CT in 9 patients and on CT/MRI scans in 10 patients. The treatment volume included the cervix, uterus, parametria, presacral space, upper vagina, pelvic, common iliac, and para-aortic nodes to the superior border of L1. All regions received 45 Gy in 25 fractions. A simultaneous or sequential boost was delivered to involved nodes (55-60 Gy in 25-30 fractions). Cisplatin was delivered weekly at a dose of 40 mg/m2. Patients were assessed for acute and late treatment-related toxicities using the NCI's CTCAE, v3.0. Response was evaluated both clinically and radiographically. Results: All patients completed the prescribed course of EFRT. All but 2 patients recieved brachytherapy. Median length of treatment was 53 days (range 36 -83). Treatment breaks for a median of 9 days (range 2-16 days) were required in 5 patients because of myelotoxicity. Three patients had their last chemotherapy cycle held because of myelotoxicity. The median follow-up for surviving patients was 18 months (5-48 months). Acute Grade 3 GI, GU and myelotoxicity was seen in 1, 1 and 10 patients, respectively. Only, one patient had late grade 3 GI toxicity. Thirty-three patients had complete response to treatment. Of these 33 patients, 11 patients (33%) developed recurrences -2 local (6%), 8 distant (24%) and 1 suburethral (3%). No patient had isolated para-aortic recurrence. Of the 19 patients with positive lymph nodes, 7 (37%) developed systemic recurrence. The 2-year actuarial pelvic control, disease-free survival and overall survival were 78%, 51% and 54%, respectively. Conclusions: EFRT using IMRT with concurrent chemotherapy was tolerated well with acceptable acute and early late toxicities. The pelvic and para-aortic control rate was good with distant metastases being the predominant site of failure in patients with nodal disease. We continue to accrue more patients and longer follow-ups in order to further extend our initial observations.
International Journal of Radiation Oncology*Biology*Physics, 2006
To assess early clinical outcome of intensity-modulated radiation therapy (IMRT) in the treatment... more To assess early clinical outcome of intensity-modulated radiation therapy (IMRT) in the treatment of vulvar cancer and compare dosimetric parameters with 3D conformal radiotherapy (3D CRT). Fifteen patients with vulvar cancer were treated with IMRT. Seven patients were treated with preoperative chemoradiation, and 8 patients were treated with adjuvant postoperative radiation therapy. Median dose was 46 Gy in the preoperative and 50.4 Gy in the postoperative group. The mean volume of small bowel, rectum, and bladder that received doses in excess of 30 Gy with IMRT was reduced when compared with 3D CRT. Treatment was well tolerated, and only 1 patient had acute Grade 3 small-bowel toxicity. Median follow-up was 12 months. In the preoperative group, 5 patients (71%) had clinical complete response and 3 patients (42.8%) had pathologic complete response. In the adjuvant group, 2 patients had recurrences in the treatment field. No patients had late Grade 3 toxicity. The 2-year actuarial disease-specific survival was 100%. Intensity-modulated RT appears to offer advantages over 3D CRT treatment of vulvar cancer by elimination of dose modulation across overlapping regions and reduction of unnecessary dose to the bladder, rectum, and small bowel. Early results with a small number of patients show promising results, with a low incidence of severe toxicity.
Uploads
Papers by Hayeon Kim