Oligometastatic adrenocortical carcinoma: definition and treatment

IBS23.01 Radiotherapy of OMD in Daily Clinical Practice

OUTCOMES OF IMAGE-GUIDED THERMAL ABLATION (IGTA) AND STEREOTACTIC BODY RADIOTHERAPY (SBRT) FOR PATIENTS WITH PULMONARY METASTASES: A SYSTEMATIC REVIEW AND META-ANALYSIS

Systemic therapy with or without local intervention for oligometastatic oesophageal squamous cell carcinoma (ESO-Shanghai 13): an open-label, randomised, phase 2 trial

Local control treatment for pulmonary metastases of colorectal cancer.

Cytoreduction and the Optimization Of Immune Checkpoint Inhibition with Radiation Therapy

Stereotactic Body Radiation Therapy Versus Conventional Radiotherapy for Hepatic Metastasis from Colorectal Carcinoma

Background: The term oligoprogression (OP) refers to a clinical scenario in which patients with diffuse metastatic disease on systemic therapy have a limited number of metastases that have progressed or are new whereas the majority of metastases are stable or improved. OP disease is increasingly being encountered in clinical practice due to improvements in systemic therapy. Treating OP disease with local ablative therapies may therefore prolong the time to more diffuse progression necessitating a change in systemic therapy and may therefore lead to improved overall survival in these patients. Only one study has evaluated the role of SBRT in patients with OP MBC. This trial accrued 47 patients with OP MBC, with 2/3 having triple negative disease. There was no difference in PFS between patients that received SBRT versus those that did not (4.2 months vs. 4.4 months, p=0.2). Whether ablative therapies are beneficial in subtypes of breast cancer that have many effective systemic therapies available, such as ER+ breast cancer, remains an open question and an unmet clinical need. Trial Design: Phase II study for patients with OP ER+ MBC (1-4 new and/or progressing metastatic lesions). Eligible patients will receive stereotactic body radiation therapy (SBRT) to the OP lesions. SBRT will be delivered to each lesion in 3-5 fractions. Each patient’s systemic therapy regimen will be held during study therapy and will resume upon completion of study therapy. Patients will then be restaged at 12 weeks post-SBSRT. Patients that have at least stable disease at that time point will continue on their systemic therapy and then be re-staged 12 weeks later (24 weeks after SBRT). This study will also study the role of ER-targeted positron emission tomography (PET) imaging with 16α-18F-Fluoro-17β-Fluroestradiol (FES) in the OP ER+ patient population with FES PET scans obtained at baseline, and at each of the 2 follow-up imaging timepoints. A key secondary hypothesis is that the use of FES PET in addition to standard imaging at baseline and in follow-up will help confirm patients have OP disease and will help assess for new lesions on subsequent restaging. Eligibility: Key inclusion criteria: age≥18 yo; histologically confirmed ER+/HER2- metastatic breast cancer; the presence of metastatic breast cancer at the time of study entry with progression in 1-4 lesions (including new lesions); SBRT must be feasible for all progressing lesions. Key Exclusion Criteria: >2 lines of systemic therapy for metastatic disease; intracranial disease progression Primary Objective: To determine whether using SBRT to treat OP lesions allows ER+ breast cancer patients to continue on their current systemic therapy for at least 24 weeks post SBRT. Select Secondary Objectives: To assess whether FES-PET increases the number of lesions found prior to SBRT; To determine the impact of SBRT on patient quality of life; time to next line systemic therapy; PFS Statistical Methods Simon 2 stage optimal design with α=0.05 and 1-β=0.80. The null hypothesis is that the proportion of patients that remain on their original systemic therapy ≥24 weeks (2 restaging scans) post-treatment is 20%. The alternative hypothesis is that the proportion of patients that remain on their original systemic therapy after 2 restaging scans is 50%. In stage 1, 8 patients that proceed to SBRT will be enrolled. The study will be terminated if only 0 or 1 subjects remain on original systemic therapy after 2 restaging scans. However, if ≥2 patients remain on original systemic therapy after 2 restaging, then an additional 10 patients would be enrolled for a total of 18 patients. The null hypothesis will be rejected if ≥6 patients remain on their original systemic therapy after 2 restaging scans.Contact Information: Jose G. Bazan (jbazan@coh.org) Funding Source: City of Hope Comprehensive Cancer Center and GE Healthcare Citation Format: Jose Bazan, Joanne Mortimer, Yun Rose Li, Rebecca Nelson, Sharon Yim. Stereotactic Body Radiation Therapy and FES PET/CT Imaging for the Treatment of Oligoprogressive Estrogen Receptor Positive Metastatic Breast Cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P3-10-30.

Background: The term oligoprogression (OP) refers to a clinical scenario in which patients with diffuse metastatic disease on systemic therapy have a limited number of metastases that have progressed or are new whereas the majority of metastases are stable or improved. OP disease is increasingly being encountered in clinical practice due to improvements in systemic therapy. Treating OP disease with local ablative therapies may therefore prolong the time to more diffuse progression necessitating a change in systemic therapy and may therefore lead to improved overall survival in these patients. Only one study has evaluated the role of SBRT in patients with OP MBC. This trial accrued 47 patients with OP MBC, with 2/3 having triple negative disease. There was no difference in PFS between patients that received SBRT versus those that did not (4.2 months vs. 4.4 months, p=0.2). Whether ablative therapies are beneficial in subtypes of breast cancer that have many effective systemic therapies available, such as ER+ breast cancer, remains an open question and an unmet clinical need. Design: Phase II study for patients with OP ER+ MBC (1-4 new and/or progressing metastatic lesions). Eligible patients will receive stereotactic body radiation therapy (SBRT) to the OP lesions. SBRT will be delivered to each lesion in 3-5 fractions. Each patient’s systemic therapy regimen will be held during study therapy and will resume upon completion of study therapy. Patients will then be restaged at 12 weeks post-SBSRT. Patients that have at least stable disease at that time point will continue on their systemic therapy and then be re-staged 12 weeks later (24 weeks after SBRT). This study will also study the role of ER-targeted positron emission tomography (PET) imaging with 16α-18F-Fluoro-17β-Fluroestradiol (FES) in the OP ER+ patient population with FES PET scans obtained at baseline, and at each of the 2 follow-up imaging timepoints. A key secondary hypothesis is that the use of FES PET in addition to standard imaging at baseline and in follow-up will help confirm patients have OP disease and will help assess for new lesions on subsequent restaging. Eligibility: Key inclusion criteria: age≥18 yo; histologically confirmed ER+/HER2- metastatic breast cancer; the presence of metastatic breast cancer at the time of study entry with progression in 1-4 lesions (including new lesions); SBRT must be feasible for all progressing lesions. Key Exclusion Criteria: >2 lines of systemic therapy for metastatic disease; intracranial disease progression Objective: To determine whether using SBRT to treat OP lesions allows ER+ breast cancer patients to continue on their current systemic therapy for at least 24 weeks post SBRT. Objective: To assess whether FES-PET increases the number of lesions found prior to SBRT; To determine the impact of SBRT on patient quality of life; time to next line systemic therapy; PFS Statistical Methods Simon 2 stage optimal design with α=0.05 and 1-β=0.80. The null hypothesis is that the proportion of patients that remain on their original systemic therapy ≥24 weeks (2 restaging scans) post-treatment is 20%. The alternative hypothesis is that the proportion of patients that remain on their original systemic therapy after 2 restaging scans is 50%. In stage 1, 8 patients that proceed to SBRT will be enrolled. The study will be terminated if only 0 or 1 subjects remain on original systemic therapy after 2 restaging scans. However, if ≥2 patients remain on original systemic therapy after 2 restaging, then an additional 10 patients would be enrolled for a total of 18 patients. The null hypothesis will be rejected if ≥6 patients remain on their original systemic therapy after 2 restaging scans. Contact Information: Jose G. Bazan (jbazan@coh.org) Funding Source: City of Hope Comprehensive Cancer Center Citation Format: Jose Bazan, Joanne Mortimer, Yun-Rose Li. A Phase II Trial of Stereotactic Body Radiation Therapy and Fluoroestradiol Positron Emission Tomography in Patients with Oligoprogressive Estrogen Receptor Positive Metastatic Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-19-05.

Treatment of Oligometastatic Non-Small Cell Lung Cancer: An ASTRO/ESTRO Clinical Practice Guideline

The purpose of the present study was to evaluate outcomes with a combination of stereotactic body radiation therapy (SBRT) for patients with hepatocellular carcinoma (HCC). The present retrospective study included 46 patients with 1-3 liver lesions with portal vein tumor thrombosis (PVTT) in 27 treated with definitive, consolidative, or salvage SBRT. The patients had Barcelona Clinic Liver Cancer (BCLC) stage A, B, or C disease (n = 44) with new, residual, progressive, or recurrent lesions with prior liver-directed and/or systemic therapy (n = 37). The median combined maximum diameter of the lesions was 7.48 cm (range, 1.55-16.5 cm). The dose fractionation for SBRT was 24-50 Gy in 5-8 fractions (median = 30 Gy in 6 fractions) with volumetric modulated arc technique on linear accelerator. Systemic treatment with sorafenib, lenvatinib, and/or nivolumab was given in 35 patients. Liver-directed interventional treatment after SBRT was given in 10 patients. Treatment response was evaluated as per mRECIST with or without Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST), and Kaplan-Meier survival analysis was performed. Patient-reported relief in symptoms was observed in 59.4% after SBRT. Of 46, 27 (58.7%) had decreased serum tumor markers with AFP and/or PIVKA-II at 3 months after SBRT with systemic treatment. The median overall survival (OS) was 21.4 months (95% CI: 14.3-28.5 months) after the index cancer diagnosis. The 6-month, 1-year, 2-year, and 3-year OS rates after diagnosis were 84.8%, 60.6%, 44.7%, and 28.2%, respectively. The median OS was 25.3 months versus 10.9 months in patients without versus with PVTT, respectively. Early response at 3-4 months after SBRT with systemic therapy (complete or partial (n = 29) versus stable or progressive (n = 17)) showed an independent association with OS (P ≤ 0.001, hazard ratio (HR) 3.88, 95% CI: 1.94-7.77). The estimated 1-year and 2-year local control rates in all patients were 94.1% and 89.6% after SBRT with systemic therapy. One patient had conversion surgery. Grade 3 hepatic toxicity during SBRT was 10.9%. Liver dysfunction with a Child-Pugh score of 2 or more points within 3 months after SBRT with systemic therapy was noted in 27.3% of patients. Late gastrointestinal toxicity was observed in 1 patient (2.17%). The present study suggested that a combination of radiotherapy with other liver-directed and/or systemic treatments is associated with favorable disease control and prolongation of survival in patients with early to advanced-stage HCC.

BackgroundLocoregional recurrence after nephrectomy for localized renal cell carcinoma (RCC) is rare with diverse manifestations. The selection criteria and efficacy of different treatments are unanswered. The objective was to compare different treatment modalities and present data on stereotactic body radiotherapy (SBRT) for recurrent RCC.Materials and MethodsPatients with locoregional recurrence after nephrectomy without distant metastasis were identified from institutional big data intelligence platform between 2001 and 2020. Patients receiving local therapy (surgery or SBRT) or systemic therapy alone (targeted therapy or PD‐1 inhibitors) were divided into two groups. Progression‐free survival (PFS) and overall survival (OS) were analyzed using Kaplan–Meier method, Cox regression model. Patients were matched with propensity score matching.ResultsAmong 106 patients, 33 (31.1%) received systemic therapy alone and 73 (68.9%) received local therapy. Local therapy was surgery in 34 patients (32.1%) and SBRT in 39 (36.8%) patients. Patients treated with systemic therapy alone had more non‐clear cell type (p = 0.044), more advanced T stage (p = 0.006), higher number (p = 0.043) but smaller size of lesions (p = 0.042). Patients receiving local therapy had significantly longer PFS than systemic therapy (19.7 vs. 7.5 months, p = 0.001). After matching, the PFS in the local therapy group remained higher (23.9 vs. 7.5 months, p = 0.001). The 2‐year OS of the local therapy group and systemic therapy group was 91.6% and 71.8%, respectively (p = 0.084). Local therapy was associated with better PFS (HR 0.37; p = 0.0003) and OS (HR 0.23; p = 0.002) in multivariate analysis. Grade 2 or higher toxicities related to local therapy occurred in nine patients.ConclusionsLocal therapy could delay disease progression compared with systemic therapy alone. SBRT is safe and effective for locally recurrent RCC.

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

Surgery and radiotherapy have been used as adjunctive treatments for women with Stage IV breast cancer and a low volume of disease, for many years. This encompasses patients with intact or recurrent disease at the primary site, as well as those with oligometastatic distant disease. The evidence to support local therapy (LT) approaches in this group of patients is largely retrospective, although randomized trials are ongoing. For patients with an intact primary tumor, over 20 retrospective analyses suggest that women undergoing primary site LT (PSLT) experience longer survival than those whose primary tumor receives no LT, with one meta-analysis of these data reporting a hazard ratio (HR) of 0.69 (95%CI 0.63, 0.77). However, a concern about selection bias as the explanation for this apparent benefit has led to several randomized trials. Two of these were reported recently, with mixed results. The design and the results of the two completed trials were different. In Mumbai, India (NCT00193778), initial therapy consisted of chemotherapy followed by randomization to PSLT or not; results showed no overall survival difference, but local control was improved in the PSLT arm. In Turkey, MF07-01 randomized Stage IV patients to PSLT or not, followed by usual systemic therapy; results suggest an improvement in overall survival at 5 years for women in the PSLT arm. Two other randomized trials are ongoing, both designed with initial systemic therapy. In the meantime, existing data do not clearly support the use of PSLT as a means of improved survival, but the local control advantage was clear in both trials, and therefore PSLT may be offered to women whose primary tumors do not respond well to systemic therapy. For women with oligometastatic disease, the data supporting LT measures is again retrospective, and consists of small, highly selected series. However, interest in LT approaches spans back many decades, and studies suggest that various strategies of surgery, radiotherapy, and more recently stereotactic body radiotherapy (SBRT), are associated with prolonged survival. The distant sites that have been subjected to these approaches include isolated metastases in lung, liver, bone, and brain. For isolated lung lesions in particular, resection also allows a clear distinction between primary and metastatic disease, since a large fraction of solitary lung lesions may in fact be primary lung tumors. In the liver, small retrospective series of highly selected patients undergoing resection suggest that longer-than-expected median survival can be observed in patients with limited disease and a long disease-free interval. Minimally invasive ablation techniques are being used with similar intent. For osseous sites, retrospective analyses of high-dose radiotherapy with ablative intent reflect similar caveats and similar results to the data on lung and liver. An important ongoing trial (NCT02364557) is randomizing women with a controlled primary tumor site and ≤2 metastatic lesions that are amenable to treatment with SBRT or surgery, to usual care or usual care with the addition LT to distant sites that must be separated by a distance of >5 cm. These ongoing studies will bring much-needed clarity to the role pf LT approaches to both the primary site and limited distant disease. Citation Format: Khan SA. Local therapy of limited disease in ABC: what is the evidence? [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr ES11-2.

Whether local therapy in the setting of metastatic cancer can affect overall survival is a matter of debate in oncologic practice. For a cancer to metastasize, it should be microscopically present in the systemic circulation, rightfully justifying the need for systemic treatment, and perhaps questioning the utility of local therapy. Nevertheless, it has been demonstrated that the reduction of disease burden through local treatment in some disease settings does improve overall survival and can lead to long-term disease control; examples include the use of radical nephrectomy in patients with diffuse renal cell carcinoma, surgical extirpation of hepatic metastases from colorectal cancer and resection of lung metastases from a variety of primary tumor sites. In the article by Iyengar et al that accompanies this editorial, the authors highlight the importance of local therapy in previously treated metastatic non–small-cell lung cancer (NSCLC). These investigators illustrate dramatic survival outcomes using stereotactic body radiation therapy (SBRT) combined with erlotinib in 24 patients who had six or fewer sites of extracranial disease and for whom platinum-based therapy had failed. With a progression-free survival of nearly 15 months and an overall survival of 20 months (improved from traditional survival rates of 2 to 4 months and 6 to 9 months, respectively), the results seem unexpected at first glance. However, when considered in the context of oligometastatic NSCLC treated with aggressive thoracic radiotherapy, these results may not be surprising, given that other series evaluating one to two sites of extrathoracic metastases have similarly revealed prolonged median survival rates of 20 to 28 months. Likewise, there are series that have incorporated a variety of primary tumor sites (ie, breast or renal) that demonstrate remarkable survival results with SBRT for five or fewer sites of metastases. Yet the single-arm nature of these studies, none of which were randomized, confounds interpretation of these results because of potential selection bias. Selecting patients who could tolerate at least one regimen of chemotherapy and were eligible for SBRT, focal and intensified radiation therapy, to all sites of disease, implies the absence of negative prognostic factors such as pleural effusion, active brain metastases, and large tumors. Patients with large tumors ( 6 cm) would have been excluded from SBRT by virtue of the conformality and dose escalation that must be achieved; in addition, tumors of this size generally fare worse. Such criteria may indicate that the favorable selection of patients can positively affect survival measures. A similar phase II study incorporated SBRT and demonstrated a lesser median survival of 14.8 months, but patients did not uniformly receive upfront chemotherapy. Chemotherapy sensitivity may likewise select for favorable disease biology. Iyengar et al used systemic therapy that consisted of erlotinib beginning 1 week before SBRT and continuing during and after SBRT until disease progression or unacceptable toxicity. Because evaluation of epidermal growth factor receptor (EGFR) mutation status was not mandatory for this clinical trial, only 54% of patients had a mutational status determined, and none harbored an EGFR mutation. However, uncertainty exists about the impact of erlotinib on the survival of the remaining patients who did not undergo mutational status determination. Although it is unlikely that targeting the EGFR mutation influenced survival outcomes and that the main source of the survival benefit was SBRT, one cannot discern the relative benefits of SBRT and the possibility that an actionable EGFR mutation affected survival in some proportion of untested patients. The authors point out that there were no significant differences in survivals between the group that had their mutational status determined versus that which did not. This is contrary to RTOG 0324, in which cetuximab was combined with chemoradiotherapy for NSCLC, and approximately 52% of patients had a specimen analysis for EGFR testing. Komaki et al showed here that patients without EGFR immunohistochemistry (IHC) had worse overall and progression-free survival compared with those with IHC data, which suggests the importance of obtaining biopsy samples for mutational analysis. This prospective phase II trial by Iyengar et al took 6 years to reach its accrual goal. The reasons for prolonged accrual at most institutions are complex, but in this situation, it calls into the question the incidence of oligometastatic NSCLC, or more importantly, how oligometastatic disease is defined. Hellman and Weichselbaum coined the term oligometastases in Journal of Clinical Oncology in 1995 to explain a clinically significant state in which there were metastases to a single or limited number of organs, an intermediary state between locally advanced disease and widespread metastatic disease. In a series by Thibault et al, the incidence of patients able to undergo SBRT for oligometastases was 17%. Mehta et al report that 74% of patients JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 32 NUMBER 34 DECEMBER 1 2014

Lung Cancer in the United Kingdom