Abstract Purpose Image guided brachytherapy (IGBT) for locally advanced cervical cancer allows dose escalation to the high-risk clinical target volume (HRCTV) while sparing organs at risk (OAR). This ...is the first comprehensive report on clinical outcome in a large multi-institutional cohort. Patients and methods From twelve centres 731 patients, treated with definitive EBRT ± concurrent chemotherapy followed by IGBT, were analysed. Kaplan–Meier estimates at 3/5 years were calculated for local control (LC, primary endpoint), pelvic control (PC), overall survival (OS), cancer specific survival (CSS). In 610 patients, G3–4 late toxicity (CTCAEv3.0) was reported. Results Median follow up was 43 months, percent of patients per FIGO stage IA/IB/IIA 22.8%, IIB 50.4%, IIIA–IVB 26.8%. 84.8% had squamous cell carcinomas; 40.5% lymph node involvement. Mean EBRT dose was 46 ± 2.5 Gy; 77.4% received concurrent chemotherapy. Mean D90 HRCTV was 87 ± 15 Gy (EQD210 ), mean D2cc was: bladder 81 ± 22 Gy, rectum 64 ± 9 Gy, sigmoid 66 ± 10 Gy and bowel 64 ± 9 Gy (all EQD23 ). The 3/5-year actuarial LC, PC, CSS, OS were 91%/89%, 87%/84%, 79%/73%, 74%/65%. Actuarial LC at 3/5 years for IB, IIB, IIIB was 98%/98%, 93%/91%, 79%/75%. Actuarial PC at 3/5 years for IB, IIB, IIIB was 96%/96%, 89%/87%, 73%/67%. Actuarial 5-year G3–G5 morbidity was 5%, 7%, 5% for bladder, gastrointestinal tract, vagina. Conclusion IGBT combined with radio-chemotherapy leads to excellent LC (91%), PC (87%), OS (74%), CSS (79%) with limited severe morbidity.
Abstract Background and purpose Currently, there is no consensus on dose prescription in image guided adaptive brachytherapy (IGABT) in locally advanced cervical cancer. The purpose of this study was ...to provide evidence based recommendations for tumor dose prescription based on results from a multi-center patient series (retroEMBRACE). Materials and methods This study analyzed 488 locally advanced cervical cancer patients treated with external beam radiotherapy ± chemotherapy combined with IGABT. Brachytherapy contouring and reporting was according to ICRU/GEC-ESTRO recommendations. The Cox Proportional Hazards model was applied to analyze the effect on local control of dose-volume metrics as well as overall treatment time (OTT), dose rate, chemotherapy, and tumor histology. Results With a median follow up of 46 months, 43 local failures were observed. Dose (D90) to the High Risk Clinical Target Volume (CTVHR ) ( p = 0.022, HR = 0.967 per Gy) was significant for local control, whereas increasing CTVHR volume ( p = 0.004, HR = 1.017 per cm3 ), and longer OTT ( p = 0.004, HR = 1.023 per day) were associated with worse local control. Histology ( p = 0.084), chemotherapy ( p = 0.49) and dose rate ( p = 1.00) did not have significant impact on local control. Separate analyses according to stage of disease showed that dose to CTVHR , residual gross tumor volume (GTVres ), and Intermediate Risk CTV (CTVIR ) has significant impact on local control. Conclusion CTVHR dose of ⩾85 Gy (D90) delivered in 7 weeks provides 3-year local control rates of >94% in limited size CTVHR (20 cm3 ), >93% in intermediate size (30 cm3 ) and >86% in large size (70 cm3 ) CTVHR . CTVIR and GTVres dose of ⩾60 Gy and ⩾95 Gy (D98) leads to similar local control. A dose of 5 Gy (CTVHR ) is required to compensate an increase of OTT by one week. Increased CTVHR volume by 10 cm3 requires additional 5 Gy for equivalent local control.
Abstract Purpose To report the prognostic factors for local control in patients treated for locally advanced cervical cancer with image guided pulsed-dose rate brachytherapy. Materials/methods ...Patients treated with curative intent by a combination of external beam radiotherapy and pulsed-dose rate brachytherapy were selected. Local failure was defined as any relapse in the cervix, vagina, parametria, or uterus during follow-up. Prognostic factors were selected based on log rank tests and then analyzed with a Cox model. Dose/effect correlations were performed using the probit model. Results Two hundred and twenty-five patients treated from 2006 to 2011 were included. According to the FIGO classification, 29% were stage IB, 58% stage II, 10% stage III, and 3% stage IVA; 95% received concomitant chemotherapy. Thirty patients were considered having incomplete response or local failure. Among the selected parameters, D90 for HR-CTV, D90 for IR-CTV, the overall treatment time, the TRAK, and the HR-CTV volume appeared significantly correlated with local control in univariate analysis. In multivariate analysis, overall treatment time >55 days and HR-CTV volume >30 cm3 appeared as independent. The probit analysis showed significant correlations between the D90 for both CTVs, and the probability of achieving local control ( p = 0.008 and 0.024). The thresholds to reach to warrant a probability of 90% of local control were 85 Gy to the D90 of the HR-CTV and 75 Gy to 90% of the IR-CTV (in 2 Gy equivalent, α / β = 10). To warrant the same local control rate, the D90 HR-CTV should be significantly increased in stage III–IV tumors, in case of HR-CTV >30 cm3 , excessive treatment time, or tumor width at diagnosis >5 cm (97, 92, 105, and 92 Gy respectively). Conclusions Overall treatment time and HR-CTV volume were independent prognostic factors for local control. The D90 for HR and IR CTV were significantly correlated with local control, and D90 HR-CTV should be adapted to clinical criteria.
Abstract Objective To report the outcomes and late toxicities of patients with locally advanced cervical cancer treated with concomitant chemoradiation (CRT) followed by intracavitary image-guided ...adaptive brachytherapy (IGABT). Methods Data from consecutive patients with histologically proven stage IB-IVA cervical cancer treated with curative intent in a single institution were analyzed. After pelvic +/− para-aortic external-beam radiation therapy, they received pulsed-dose rate IGABT following GEC-ESTRO recommendations. Results Two hundred and twenty-five patients were enrolled. Sixty-five percent were stage ≥ IIB according to FIGO classification. Ninety-five percent received CRT. Mean D90 to HR and IR-CTV were 80.4 +/− 10.3 Gy and 67.7 +/− 6.1 Gy. After a median follow-up of 38.8 months, 3-year local control and overall survival rates were 86.4% and 76.1%, respectively. A trend for a detrimental effect of tumor stage on local control rates was observed with 3-year local control rates of 100% for stages IB1 and IIA, 90.5 for IB2, 85.8% for IIB, 50% for IIIA, 77.1 for IIIB, and 66.7% for IVA tumors (p = 0.06). Local control rates at 3 years were 95.6% in the group of patients with D90 of HR-CTV ≥ 85 Gy, 88.8% in those with D90 between 80 and 85 Gy, and 80% when D90 < 80 Gy (p = 0.018). Eighteen severe late gastrointestinal and urinary effects affecting 14 patients were reported corresponding with a crude incidence of 6.6%. Conclusions CRT followed by IGABT provides high local control rates with limited toxicity. Reaching high doses is mandatory to achieve local control and interstitial brachytherapy is necessary in advanced diseases.
Learning Objectives
Evaluate control rates of IGABT combined with CCRT for the treatment of locally advanced cervical cancer.
Describe survival outcomes in patients treated with IGABT combined with ...CCRT for locally advanced cervical cancer.
Describe toxicities in patients treated with IGABT combined with CCRT for locally advanced cervical cancer.
Purpose.
To evaluate the outcomes of patients with locally advanced cervical cancer treated with three‐dimensional image‐guided brachytherapy (IGABT) after concomitant chemoradiation (CCRT).
Materials and Methods.
Data from patients treated with CCRT followed by magnetic resonance imaging‐guided or computed tomography‐guided pulsed‐dose‐rate brachytherapy, performed according to the Groupe Européen de Curiethérapie–European Society for Radiotherapy and Oncology guidelines, were reviewed. At first, stage I or II patients systematically underwent radical hysterectomy or were offered a randomized study evaluating hysterectomy. Then, hysterectomy was limited to salvage treatment.
Results.
Of 163 patients identified, 27% had stage IB, 57% had stage II, 12% had stage III, and 3% had stage IVA disease. The mean dose delivered (in 2‐Gy dose equivalents) to 90% of the high‐risk clinical target volume was 78.1 ± 9.6 Gy, whereas the doses delivered to organs at risk were maintained under the usual thresholds. Sixty‐one patients underwent a hysterectomy. Macroscopic residual disease was found in 13 cases. With a median follow‐up of 36 months (range, 5–79 months), 45 patients had relapsed. The 3‐year overall survival rate was 76%. Local and pelvic control rates were 92% and 86%, respectively. According to the Common Toxicity Criteria 3.0, 7.4% of patients experienced late grade 3 or 4 toxicity. Most of those had undergone postradiation radical surgery (2.9% vs. 14.8; p = .005).
Conclusion.
IGABT combined with CCRT provides excellent locoregional control rates with low treatment‐related morbidity, justifying the elimination of hysterectomy in the absence of obvious residual disease. Distant metastasis remains an important first relapse and may warrant more aggressive systemic treatment.
The outcomes of patients with locally advanced cervical cancer treated with three‐dimensional image‐guided brachytherapy after concomitant chemoradiation were evaluated. An excellent locoregional control rate with low treatment‐related morbidity was observed, justifying the elimination of hysterectomy in the absence of obvious residual disease.
Abstract Objective To report clinical results of a multimodal strategy based on preoperative brachytherapy followed with surgery in early stage cervical cancer. Materials/Methods The outcome of ...consecutive patients receiving brachytherapy in our Institution for an early stage IB1-IIA1 invasive cervical cancer with risk factors (lymphovascular embols and/or tumor > 2 cm) between 2000 and 2013 was analyzed. The treatment consisted of preoperative low dose or pulse dose-rate utero-vaginal brachytherapy followed, 6–8 weeks later, by a radical hysterectomy/bilateral salpingo-oophorectomy plus pelvic ± para-aortic lymph node dissection. A postoperative chemoradiation was delivered in patients with histological evidence of lymph nodes metastases. Results 182 patients were identified. Histological examination of hysterectomy specimen showed the presence of a tumor residuum in 55 patients (30.2%). One patient (0.5%) had residual tumor cells in the parametria. With a median follow-up of 5.3 years, 14 patients (7.7%) presented tumor relapse, including three (1.6%) local relapses. Five-year disease-free survival (DFS) rate was 93.6% (95%CI: 91.6–95.6%). In log-rank analysis, presence of pelvic nodal metastases at time of lymphadenectomy (p = 0.001) and tumor size ≥ 3 cm (p = 0.003) correlated with a poorer DFS. Presence of a tumor residuum on hysterectomy specimen correlated with a higher risk of pelvic or para-aortic failure (p = 0.035). A time interval > 10 weeks between brachytherapy and surgery correlated with a higher risk of failure outside the pelvis (p = 0.003). Significant postoperative complications were reported in 16 patients (8.8%). All delayed toxicities were mild to moderate. Conclusions A preoperative brachytherapy is a safe and effective option in early stage cervical cancer.
In Regard to Swanick et al Mazeron, Renaud; Rivin Del Campo, Eleonor; Haie-Meder, Christine ...
International journal of radiation oncology, biology, physics,
03/2017, Letnik:
97, Številka:
3
Journal Article
Summary Radiotherapy plays a key role in the management of early stage and locally advanced head and neck squamous-cell carcinomas (HNSCC) either alone or, more frequently combined with surgery ...and/or chemotherapy. Several approaches have been developed to improve its efficacy while maintaining acceptable toxicities, such as altered fractionated radiotherapy or concomitant chemoradiotherapy which have both improved the anti-tumor efficacy of radiotherapy. Of particular interest is concomitant chemoradiotherapy (CT-RT) which is the most commonly used approach in locally advanced disease. Taxanes and platinum-based induction chemotherapy could constitute an option in the treatment of locally advanced HNSCC and it’s contribution before concomitant RT-CT is currently under investigation. More recently, epidermal growth factor receptor (EGFr) molecular targeting with cetuximab combined with radiotherapy has been successfully tested in a large randomized trial and this combination constitutes a new option, especially for patients with medical co-morbidities. Finally management of treatment related acute or late toxicity remains an important issue and in the last decade major achievements have been obtained in this field especially using intensity modulated radiotherapy (IMRT).
This study assessed outcomes following the nowadays standing treatment for primary vaginal cancer with radio(chemo)therapy and image-guided adaptive brachytherapy (IGABT) in a multicenter patient ...cohort.
Patients treated with computer tomography (CT)-MRI-assisted-based IGABT were included. Retrospective data collection included patient, tumor and treatment characteristics. Late morbidity was assessed by using the CTCAE 3.0 scale.
Five European centers included 148 consecutive patients, with a median age of 63 years. At a median follow-up of 29 months (IQR 25-57), two- and five-year local control were 86% and 83%; disease-free survival (DFS) was 73% and 66%, and overall survival (OS) was 79% and 68%, respectively. Crude incidences of ≥ grade-three urogenital, gastro-intestinal and vaginal morbidity was 8%, 3% and 8%, respectively. Lymph node metastasis was an independent prognostic factor for disease-free survival (DFS). Univariate analysis showed improved local control in patients with T2-T4 tumors if >80 Gy EQD2
was delivered to the clinical target volume (CTV) at the time of brachytherapy.
In this large retrospective multicenter study, IGABT for primary vaginal cancer resulted in a high local control with acceptable morbidity. These results compared favorably with two-dimensional (2D) radiograph-based brachytherapy and illustrate that IGABT plays an important role in the treatment of vaginal cancer.
To determine predictive factors of late radiation fibrosis (RF) after conformal radiotherapy (3D-RT) in non-small cell lung cancer (NSCLC).
Ninety-six patients with Stage IA-IIIB NSCLC were included ...in a prospective trial. Clinical evaluation, chest X-ray, and pulmonary functional tests including diffusion parameters were performed before and 6 months after radiotherapy. An independent panel of experts prospectively analyzed RF, using Late Effects in Normal Tissues-Subjective, Objective, Management and Analytic scales classification. Logistic regression analysis was performed to identify relationships between clinical, functional, or treatment parameters and incidence of RF. Variations of circulating serum levels of pro-inflammatory (interleukin-6, tumor necrosis factor alpha, tumor growth factor beta1) and anti-inflammatory (interleukin-10) cytokines during 3D-RT were examined to identify correlations with RF.
Of the 96 patients included, 72 were evaluable for RF at 6 months. Thirty-seven (51.4%) developed RF (Grade >or=1), including six severe RF (Grades 2-3; 8.3%). In univariate analysis, only poor Karnofsky Performance Status and previous acute radiation pneumonitis were associated with RF (p < 0.05). Dosimetric factors (mean lung dose, percentage of lung volume receiving more than 10, 20, 30, 40, and 50 Gy) were highly correlated with RF (p < 0.001). In multivariate analysis, previous acute radiation pneumonitis and dosimetric parameters were significantly correlated with RF occurrence. It was not significantly correlated either with cytokines at baseline or with their variation during 3D-RT.
This study confirms the importance of dosimetric parameters to limit the risk of RF. Contrary to acute radiation pneumonitis, RF was not correlated to cytokine variations during 3D-RT.
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