Stereotactic Body Radiation Therapy for Oligometastatic Ovarian Cancer: A Step Toward a Drug Holiday

Lazzari, Roberta; Ronchi, Sara; Gandini, Sara; Surgo, A.; Volpe, Stefania; Piperno, Gaia; Comi, S.; Pansini, F.; Fodor, C.; Orecchia, Roberto; Tomao, Federica; Parma, Gabriella; Colombo, Nicoletta; Jereczek‐Fossa, Barbara Alicja

doi:10.1016/j.ijrobp.2018.03.058

Cited by 66 publications

(70 citation statements)

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“…As far as the primary endpoint is concerned, we documented a rate of 65.2% CR of irradiated lesions; despite the limits inherent to the heterogeneity over time of frequency and type of imaging for assessment of clinical response, our finding well matches with data of some OC SBRT series . The 100% rate of CR reported by Trippa et al is likely to be ascribed to the small sample size and/or the inclusion of only lymph node disease, which is recognized as presenting a higher response to SBRT compared with parenchymal lesions . A comprehensive summary of the literature focused on SBRT in ovarian cancer is reported in supplemental online Table 2.…”

Section: Discussionsupporting

confidence: 81%

“…The independent favorable role of younger age and lower tumor volume (PTV) in predicting CR has been already reported by other studies . Conversely, lymph node lesions showed a higher responsiveness compared with parenchymal disease, and this behavior was confirmed in all settings originated from the combinations of variables identified by the multivariate analysis; similar findings have been mentioned in the literature, but these are few , and a comprehensive evaluation of this issue is lacking. In the context of the personalized medicine, further insights on intrinsic biomolecular features of lymph node and parenchymal lesions would be of interest considering that in our series this variable has emerged as the most powerful independent predictor of CR.…”

Section: Discussionsupporting

confidence: 54%

“…In addition, SBRT has been attempted even in unexpected settings, such as OC, which has been considered for years as not susceptible to benefit of a local treatment because of common documentation of diffuse abdominal disease . There are only a few studies focusing on the role of SBRT in patients with metastatic, persistent, recurrent (MPR)‐OC ; in addition, the relatively small size of some series and adoption of several SBRT schedules did not allow definition of the optimal total dose, dose per fraction, and referral dose point, as for other solid tumors .…”

Section: Introductionmentioning

confidence: 99%

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A Large, Multicenter, Retrospective Study on Efficacy and Safety of Stereotactic Body Radiotherapy (SBRT) in Oligometastatic Ovarian Cancer (MITO RT1 Study): A Collaboration of MITO, AIRO GYN, and MaNGO Groups

et al. 2019

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Background. Recent studies have reported improvement of outcomes (progression-free survival, overall survival, and prolongation of androgen deprivation treatment-free survival) with stereotactic body radiotherapy (SBRT) in nonsmall cell lung cancer and prostate cancer. The aim of this retrospective, multicenter study (MITO RT-01) was to define activity and safety of SBRT in a very large, real-world data set of patients with metastatic, persistent, and recurrent ovarian cancer (MPR-OC).Materials and Methods. The endpoints of the study were the rate of complete response (CR) to SBRT and the 24-month actuarial local control (LC) rate on "per-lesion" basis. The secondary endpoints were acute and late toxicities and the 24-month actuarial late toxicity-free survival. Objective response rate (ORR) included CR and partial response (PR). Clinical benefit (CB) included ORR and stable disease (SD). Toxicity was evaluated by the Radiation Therapy Oncology Group (RTOG) and the The Oncologist 2020;25:e311-e320 www.TheOncologist.com Radiation Oncology(EORTC) and Common Terminology Criteria for Adverse Events (CTCAE) scales, according to center policy. Logistic and Cox regression were used for the uni-and multivariate analysis of factors predicting clinical CR and actuarial outcomes. Results. CR, PR, and SD were observed in 291 (65.2%), 106 (23.8%), and 33 (7.4%) lesions, giving a rate of CB of 96.4%. Patient aged ≤60 years, planning target volume (PTV) ≤18 cm 3 , lymph node disease, and biologically effective dose α/β10 > 70 Gy were associated with higher chance of CR in the multivariate analysis. With a median follow-up of 22 months (range, 3-120), the 24-month actuarial LC rate was 81.9%. Achievement of CR and total dose >25 Gy were associated with better LC rate in the multivariate analysis. Mild toxicity was experienced in 54 (20.7%) patients; of 63 side effects, 48 were grade 1, and 15 were grade 2. The 24-month late toxicity-free survival rate was 95.1%.Conclusions. This study confirms the activity and safety of SBRT in patients with MPR-OC and identifies clinical and treatment parameters able to predict CR and LC rate. The Oncologist 2020;25:e311-e320Implications for Practice: This study aimed to define activity and safety of stereotactic body radiotherapy (SBRT) in a very large, real life data set of patients with metastatic, persistent, recurrent ovarian cancer (MPR-OC). Patient age <60 years, PTV <18 cm 3 , lymph node disease, and biologically effective dose α/β10 >70 Gy were associated with higher chance of complete response (CR). Achievement of CR and total dose >25 Gy were associated with better local control (LC) rate. Mild toxicity was experienced in 20.7% of patients. In conclusion, this study confirms the activity and safety of SBRT in MPR-OC patients and identifies clinical and treatment parameters able to predict CR and LC rate.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionsupporting

confidence: 54%

Section: Introductionmentioning

confidence: 99%

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A Large, Multicenter, Retrospective Study on Efficacy and Safety of Stereotactic Body Radiotherapy (SBRT) in Oligometastatic Ovarian Cancer (MITO RT1 Study): A Collaboration of MITO, AIRO GYN, and MaNGO Groups

et al. 2019

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“…In this context, radiotherapy can enhance the immune response against EOC and the effects of immunotherapy. Recently, some authors have demonstrated a role of radiotherapy alone in oligometastatic EOC [68][69][70], and some clinical studies are evaluating the efficacy and safety of checkpoints combined with radiotherapy. The most effective radiotherapy dosage and fractionation to obtain the activation of the immune response are still to be defined.…”

Section: Radiotherapy and Immune Checkpoint Inhibitormentioning

confidence: 99%

Immune Checkpoint Inhibitors in Epithelial Ovarian Cancer: An Overview on Efficacy and Future Perspectives

et al. 2020

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Epithelial ovarian cancer (EOC) is the leading cause of death among gynecological cancers. Despite improvements in medical treatments, the prognosis for EOC remains poor, and there is an urgent need for new therapeutic strategies. Immune checkpoint inhibitors (CPIs) have dramatically improved survival of several cancers and are under evaluation in OC. Unfortunately, CPIs have shown globally unsatisfactory results. The aim of this manuscript is to critically review the results from early-phase trials with CPIs in terms of safety and activity, discuss the possible reasons for disappointing results and the new therapeutic approaches to improve patient outcomes. However, despite the success of immunotherapy in other malignancies such as in melanoma, non-small cell lung cancer (NSCLC) and urothelial cancers [25,26], the use of antibodies inhibiting the immune checkpoint programmed cell death (PD-1) or its ligand (PD-L1) obtained modest results in EOC so far, with median response rates of 10% up to 15% [18][19][20]27].Interestingly, the combination of the anti-PD1 nivolumab and the anti-lymphocyte-associated protein 4 (anti-CTLA4) ipilimumab showed promising results in platinum-resistant EOC at six-month interim analyses with an overall response rate (ORR) of 34% (doubling the results of nivolumab monotherapy). However, final results are still awaited [28].As a consequence, no immunotherapeutic agent has obtained regulatory approval for EOC thus far. PD1/PD-L1

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“…In 69.5% of patients, no acute or late toxicities were observed. 23% of patients experienced acute grade 1 or 2 GI (gastrointestinal) toxicity, 28% of patients experienced grade 1 or 2 GI toxicity, or grade 1 genitourinary toxicity [13].…”

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confidence: 99%

Rethinking the Role of Radiation Therapy in the Management of Epithelial Ovarian Cancer

Jacobson

Galvan-Turner

2020

Diagnostics

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Radiation has been relegated to a palliative role in the management of epithelial ovarian cancer (EOC). Contemporary radiation techniques, including intensity modulated radiation therapy (IMRT), stereotactic body radiation therapy (SBRT), and image-guided radiation therapy, enable conformal treatment that controls local disease with minimal morbidity. Recent studies from multiple institutions support the role of radiation in the ablative treatment of oligometastatic disease and control of locally recurrent and metastatic disease. Effective local treatment with radiation complements the role of systemic therapy in the management of EOC; reduces symptoms and disease burden, and may contribute to a prolonged drug free interval.

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Stereotactic Body Radiation Therapy for Oligometastatic Ovarian Cancer: A Step Toward a Drug Holiday

Abstract: SBRT for oligometastatic ovarian cancer showed good local control and a good toxicity profile. It might be an appealing alternative to other invasive local therapies to delay systemic therapy in the case of chemorefractory disease or intolerance to systemic agents.

Cited by 66 publications

References 33 publications

A Large, Multicenter, Retrospective Study on Efficacy and Safety of Stereotactic Body Radiotherapy (SBRT) in Oligometastatic Ovarian Cancer (MITO RT1 Study): A Collaboration of MITO, AIRO GYN, and MaNGO Groups

A Large, Multicenter, Retrospective Study on Efficacy and Safety of Stereotactic Body Radiotherapy (SBRT) in Oligometastatic Ovarian Cancer (MITO RT1 Study): A Collaboration of MITO, AIRO GYN, and MaNGO Groups

Immune Checkpoint Inhibitors in Epithelial Ovarian Cancer: An Overview on Efficacy and Future Perspectives

Rethinking the Role of Radiation Therapy in the Management of Epithelial Ovarian Cancer

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