Long-term outcomes of intensity-modulated radiation therapy (IMRT) and high dose rate brachytherapy as adjuvant therapy after radical hysterectomy for cervical cancer.

Compared with 3D-planned pelvic radiation, intensity-modulated radiation therapy (IMRT) has been shown to reduce acute toxicity in cervical cancer patients after radical hysterectomy. This study evaluated late toxicity and patterns of failure after post-operative pelvic IMRT interdigitated weekly with high dose rate brachytherapy. This retrospective study included 53 cervical cancer patients treated between January 2006 and August 2019 with radical hysterectomy, lymphadenectomy, and post-operative IMRT and high dose rate brachytherapy. The decision to include chemotherapy was made by the treating gynecologic oncologist based on patient-specific criteria including positive pelvic lymph nodes, positive surgical margins, or positive parametrial invasion. The actuarial rates of genitourinary and gastrointestinal toxicity, vaginal cuff/regional nodal/distant failure, and overall survival were calculated using the Kaplan-Meier method. Median follow-up was 70 months (range 5.4-148) months and age at diagnosis was 47 (range 24-73) years. The 2018 International Federation of Gynecology and Obstetrics (FIGO) clinical stages were IB1 (n=19), IB2 (n=7), IIB (n=7), IIIC1 (n=19), and IIIC2 (n=1). Median radiation dose delivered in 160 cGy daily fractions was 5120 (range 4640-5120) cGy. Median brachytherapy dose prescribed to the vaginal surface delivered in six weekly fractions was 2400 (range 1200-4800) cGy. Concurrent chemotherapy was delivered in 35 (66%) patients. There were no acute grade >3 genitourinary or gastrointestinal toxicities. Late grade >3 occurred in two (3.8%) patients, including a small bowel obstruction and a ureteral stricture. The 5-year actuarial rate for gastrointestinal or genitourinary toxicity was 1.9%. There were no vaginal cuff recurrences. The 5-year actuarial rates for regional nodal failure, distant failure outside the radiation field, any failure, and overall survival were 11%, 11%, 14%, and 85%, respectively. Post-operative IMRT with high dose rate brachytherapy for patients with cervical cancer is associated with excellent outcomes and limited rates of radiation-related non-hematologic toxicity.

Contreras J ，Srivastava A ，Chundury A ，Schwarz JK ，Markovina S ，Thaker PH ，Massad LS ，Mutch DG ，Powell MA ，Grigsby PW ，Lin AJ ... -  《-》

Intensity modulated radiation therapy boost in locally-advanced cervical cancer in the absence of brachytherapy.

Standard treatment in locally-advanced cervical cancer is external beam radiotherapy concomitant with platinum-based chemotherapy, followed by brachytherapy. The goal of our study was to determine whether an intensity modulated radiation therapy (IMRT) boost is feasible in patients unfit for brachytherapy. We retrospectively analyzed data of 25 patients unfit for brachytherapy with median age 55 years (range, 30-82) with locally-advanced/metastatic cervical cancer who underwent external beam radiotherapy to pelvis ±para-aortic lymph nodes and sequential IMRT boost between July 2014 and December 2017. Total dose of 45-50.4 Gy in 25-28 fractions (1.8 Gy/fraction) was administered to the cervix, uterus, parametria, ovaries, vaginal tissues (based on vaginal extension), involved lymph nodes, or relevant draining lymph-nodal groups. Para-aortic nodes were included if involved at radiological staging or if common iliac nodes were positive. The IMRT boost included all residual tumor after external beam radiotherapy identified on MRI. The Kaplan-Meier method was used to calculate 2 years' overall survival, 2 years' progression-free survival, and 2 years' local control. Overall survival- and progression-free survival were calculated considering the starting of radiotherapy or neo-adjuvant chemotherapy if prescribed, while local control was calculated from the end of radiotherapy. Median radiation dose to pelvis ±para-aortic lymph nodes was 50.4 Gy (45-50.4), boost treatment was homogeneously performed to a total dose of 25 Gy in five fractions every other day.After a median follow-up of 26 months (range, 4-77), tumor persistence at cervix at 6 months from the end of radiotherapy or local recurrence occurred in five women (20%), eight (32%) experienced a further distant progression (two of them had also tumor persistence). Two-year local control and overall survival rates for all stages were 78% and 67%, respectively. According to Common Terminology Criteria for Adverse Events v.4 scoring criteria, 10 patients experienced gastrointestinal and/or genitourinary grade G1-2 acute toxicity. G2 rectal late toxicity requiring laser-coagulation was registered in two patients, there were no gastrointestinal and/or genitourinary acute or late toxicities≥G3. The combination of external beam radiotherapy and brachytherapy remains the standard of care, however our preliminary data show the feasibility of IMRT boost in terms of toxicity with promising results in terms of local control and overall survival.

Lazzari R ，Riva G ，Augugliaro M ，Vavassori A ，Dicuonzo S ，Cattani F ，Comi S ，Colombo N ，Jereczek-Fossa BA ... -  《-》

Low-dose, prophylactic, extended-field, intensity-modulated radiotherapy plus concurrent weekly cisplatin for patients with stage IB2-IIIB cervical cancer, positive pelvic lymph nodes, and negative para-aortic lymph nodes.

Liang JA ，Chen SW ，Hung YC ，Yeh LS ，Chang WC ，Lin WC ，Chang YY ... -  《-》

Neoadjuvant radiotherapy and brachytherapy in endometrial cancer with gross cervical involvement: a CHIRENDO research group study.

Historically, radical hysterectomy followed by adjuvant radiotherapy has been offered to patients with endometrial cancer who have gross cervical involvement; however, this approach is known to carry considerable morbidity. Neoadjuvant radiotherapy followed by extra-fascial hysterectomy has been proposed as an alternative treatment but has been poorly studied to date. To evaluate the locoregional control rate associated with neoadjuvant radiotherapy followed by extra-fascial hysterectomy. A retrospective cohort study of 30 patients with endometrial cancer with gross cervical involvement treated between May 2006 and January 2016 was performed. Eligible patients were those aged >18 years with non-metastatic endometrial adenocarcinoma and gross cervical disease treated with curative intent at the Centre hospitalier de l'Université de Montréal. Treatment protocol consisted of pelvic neoadjuvant radiotherapy and high-dose rate brachytherapy followed by extra-fascial hysterectomy. Kaplan-Meier curves were used for survival analysis. The median age was 60 (range 37-82) and median body mass index was 32 kg/m2 (range 16-55). Twenty-four (80%) patients were diagnosed with a positive cervical/endocervical biopsy. Clinical staging confirmed 36.7% (n=11) as stage II, 20% (n=6) stage IIIB, 30% (n=9) stage IIIC1, and 13.3% (n=4) stage IIIC2. Seventy-seven per cent (n=23) of patients had an endometrioid histology. Locally advanced disease was identified by imaging alone in six patients. Rates of parametrial, adnexal, vaginal, and nodal invasion were 10% (n=3), 6.7% (n=2), 13.3% (n=4), and 43.3% (n=13) at diagnosis, respectively. All patients completed pelvic radiotherapy (13.3% extended field) and 90% received brachytherapy. Twenty per cent (n=6) of surgeries were performed using minimal invasive technique. On surgical specimen, 63.3% (n=19) had complete cervical response, 90% (n=27) had negative margins, and 10% (n=3) had residual nodal involvement. Median follow-up time was 62 months (range 1-120). Six recurrences were identified; all except one involved distant failure, and two with locoregional failure. Five-year locoregional control rate, disease-free, overall, and disease-specific survival were 90.5%, 78.5%, 92.6%, and 96.2%, respectively. Two patients (6.7%) had grade 3+ acute radiation-related complications (all grade 3). Grade 3+ post-operative morbidity was noted in 2 (6.7%) patients. Neoadjuvant radiotherapy followed by extra-fascial hysterectomy offers good locoregional control with low treatment-related morbidity in patients with endometrial cancer with overt cervical involvement.

Brodeur MN ，Samouëlian V ，Dabi Y ，Cormier B ，Beauchemin MC ，Barkati M ... -  《-》

A phase I study of concurrent weekly carboplatin and paclitaxel combined with intensity-modulated pelvic radiotherapy as an adjuvant treatment for early-stage cervical cancer patients with positive pelvic lymph nodes.

Mabuchi S ，Takahashi R ，Isohashi F ，Yokoi T ，Ito K ，Tsutui T ，Ogata T ，Yoshioka Y ，Ogawa K ，Kimura T ... -  《-》