Search

Aims: To investigate whether the addition of radiotherapy could be an appropriate option to delay the time-to-next systemic treatment (TTNsT) in patients with oligoprogressive solid tumors who had acquired or innate resistance to immune checkpoint inhibitors (ICIs). Material and methods: Patients with oligoprogressive disease treated with ICIs and radiotherapy at our Institute from January 2019 to June 2023 were retrospectively identified. Patients were stratified as primary or secondary immunorefractory according to the time of onset of ICI resistance. TTNsT and Time-To-Resistance (TTR) were the primary outcomes. Secondary outcomes included: post-radiotherapy first progression-free survival (pR-PFS), Local Control (LC), Overall Survival (OS), and treatment-related toxicities. In addition, out-of-field effects (such as the abscopal effect) of radiotherapy have been hypothesized. The survival rates were analyzed using the Kaplan–Meier method and long-rank test. Results: 40 out of 105 screened patients with oligoprogressive disease met the inclusion criteria. Of these, 28 had an acquired drug resistance while 12 had an innate drug resistance. Radiotherapy was offered as a local treatment approach in all patients. RT techniques were classified into three regimens: standard palliative hypofractionated radiotherapy (hypo-RT), stereotactic radiotherapy (SRS/SBRT), and lattice radiotherapy (LRT). After a median follow-up of 22.5 months, the median TTR was 4 months (range 3–4) in patients with innate resistance vs 14 months (range 7–36) in patients with acquired resistance. Median TTNsT among patients with acquired and those with innate resistance was not reached (NR) vs 24 months (range 7–72). Overall, only six patients suffered from a local failure. Although out-of-field effects of radiotherapy were hypothesized, we were unable to record them as they did not occur during the observation period. Regardless of the radiation dose, there was no observable ≥ Grade 2 acute or late treatment-related toxicity. Conclusion: Our preliminary results seem to confirm that the integration of radiotherapy and ICIs may allow for the continuation of systemic therapy beyond progression, which can have a subsequent benefit in terms of survival outcomes even in patients with innate resistance. [ABSTRACT FROM AUTHOR]

Abstract Aims To investigate whether the addition of radiotherapy could be an appropriate option to delay the time-to-next systemic treatment (TTNsT) in patients with oligoprogressive solid tumors who had acquired or innate resistance to immune checkpoint inhibitors (ICIs). Material and methods Patients with oligoprogressive disease treated with ICIs and radiotherapy at our Institute from January 2019 to June 2023 were retrospectively identified. Patients were stratified as primary or secondary immunorefractory according to the time of onset of ICI resistance. TTNsT and Time-To-Resistance (TTR) were the primary outcomes. Secondary outcomes included: post-radiotherapy first progression-free survival (pR-PFS), Local Control (LC), Overall Survival (OS), and treatment-related toxicities. In addition, out-of-field effects (such as the abscopal effect) of radiotherapy have been hypothesized. The survival rates were analyzed using the Kaplan–Meier method and long-rank test. Results 40 out of 105 screened patients with oligoprogressive disease met the inclusion criteria. Of these, 28 had an acquired drug resistance while 12 had an innate drug resistance. Radiotherapy was offered as a local treatment approach in all patients. RT techniques were classified into three regimens: standard palliative hypofractionated radiotherapy (hypo-RT), stereotactic radiotherapy (SRS/SBRT), and lattice radiotherapy (LRT). After a median follow-up of 22.5 months, the median TTR was 4 months (range 3–4) in patients with innate resistance vs 14 months (range 7–36) in patients with acquired resistance. Median TTNsT among patients with acquired and those with innate resistance was not reached (NR) vs 24 months (range 7–72). Overall, only six patients suffered from a local failure. Although out-of-field effects of radiotherapy were hypothesized, we were unable to record them as they did not occur during the observation period. Regardless of the radiation dose, there was no observable ≥ Grade 2 acute or late treatment-related toxicity. Conclusion Our preliminary results seem to confirm that the integration of radiotherapy and ICIs may allow for the continuation of systemic therapy beyond progression, which can have a subsequent benefit in terms of survival outcomes even in patients with innate resistance.

Abstract Background Standard treatment options for patients with metastatic urothelial cancer (mUC) include systemic platinum-based chemotherapy, immunotherapy, antibody-drug-conjugates, and targeted therapy. Oligometastatic disease (OMD) may be an intermediate state between localized and generalized cancer. The best treatment strategy for OMD and oligoprogressive (OPD) disease is poorly studied in mUC but local stereotactic body radiation therapy (SBRT) could be an option to avoid or delay systemic treatment. The aim of this study was to assess the efficacy and feasibility of SBRT given in a real-world patient population. Methods All patients with mUC treated with SBRT at Karolinska University Hospital, Stockholm, Sweden between 2009 and 2022 were included in this study. Baseline clinical characteristics, treatment data, SBRT dosimetry data and treatment outcome were collected retrospectively. The study endpoints were local control rate (LCR), progression-free-survival (PFS), overall survival (OS) and feasibility of SBRT. Results In total 39 patients were treated with SBRT. The median follow-up was 25.6 months. The LCR was 82%. PFS and OS were 4.1 and 26.2 months, respectively. Treatment was well tolerated; all patients but one (treatment related pain) completed the planned SBRT. Number of metastases irradiated with SBRT was significantly associated with outcome; patients with only one irradiated lesion had more favourable PFS compared to individuals with 2 or more metastases (HR 4.12, 95% CI: 1.81–9.38, p = 0.001). A subgroup of patients (15%) achieved a sustained long-term survival benefit and never required systemic treatments after SBRT. Conclusions SBRT was well tolerated and associated with high LCR. A subpopulation of patients with single metastatic lesion achieved long-term OS and never required subsequent systemic treatment after SBRT. Prospective randomized studies are warranted to discover treatment predictive biomarkers and to investigate the role of SBRT in oligometastatic UC.

Background: Standard treatment options for patients with metastatic urothelial cancer (mUC) include systemic platinum-based chemotherapy, immunotherapy, antibody-drug-conjugates, and targeted therapy. Oligometastatic disease (OMD) may be an intermediate state between localized and generalized cancer. The best treatment strategy for OMD and oligoprogressive (OPD) disease is poorly studied in mUC but local stereotactic body radiation therapy (SBRT) could be an option to avoid or delay systemic treatment. The aim of this study was to assess the efficacy and feasibility of SBRT given in a real-world patient population. Methods: All patients with mUC treated with SBRT at Karolinska University Hospital, Stockholm, Sweden between 2009 and 2022 were included in this study. Baseline clinical characteristics, treatment data, SBRT dosimetry data and treatment outcome were collected retrospectively. The study endpoints were local control rate (LCR), progression-free-survival (PFS), overall survival (OS) and feasibility of SBRT. Results: In total 39 patients were treated with SBRT. The median follow-up was 25.6 months. The LCR was 82%. PFS and OS were 4.1 and 26.2 months, respectively. Treatment was well tolerated; all patients but one (treatment related pain) completed the planned SBRT. Number of metastases irradiated with SBRT was significantly associated with outcome; patients with only one irradiated lesion had more favourable PFS compared to individuals with 2 or more metastases (HR 4.12, 95% CI: 1.81–9.38, p = 0.001). A subgroup of patients (15%) achieved a sustained long-term survival benefit and never required systemic treatments after SBRT. Conclusions: SBRT was well tolerated and associated with high LCR. A subpopulation of patients with single metastatic lesion achieved long-term OS and never required subsequent systemic treatment after SBRT. Prospective randomized studies are warranted to discover treatment predictive biomarkers and to investigate the role of SBRT in oligometastatic UC. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the ability of radiotherapy (RT) to prolong progression-free survival (PFS) and to report treatment-related toxicities among oligoprogressive metastatic Merkel cell carcinoma (mMCC) patients on avelumab. Methods: We retrospectively collected clinical data on mMCC patients who underwent radiotherapy for limited progression on avelumab. Patients were categorized as primary or secondary immune refractory depending on the time of onset of resistance to immunotherapy (at the first or subsequent follow-up visits after avelumab initiation). Pre- and post-RT PFS were calculated. Overall survival (OS) from the first progression treated with RT was also reported. Radiological responses and toxicities were evaluated according to the irRECIST criteria and RTOG scoring system, respectively. Results: Eight patients, including five females, with a median age of 75 years, met our inclusion criteria. The median gross tumor and clinical target volumes at first progression on avelumab were 29.85 cc and 236.7 cc, respectively. The treatment sites included lymph node, skin, brain, and spine metastases. Four patients received more than one course of RT. Most patients were treated with palliative radiation doses (mainly 30 Gy in 3 Gy/day fractions). Two patients were treated with stereotactic RT. Five/eight patients were primary immune refractory. The objective response rate at the first post-RT assessment was 75%, whereas no local failure was reported. The median pre-RT PFS was 3 months. The pre-RT PFS was 37.5% at 6 months and 12.5% at 1 year. The median post-RT PFS was not reached. The post-RT PFS was 60% at 6 months and 1 year. The post-RT OS was 85.7% at 1 year and 64.3% at 2 years. No relevant treatment-related toxicity was observed. After a median follow-up of 18.5 months, 6/8 patients are still alive and continuing on avelumab therapy. Conclusions: Adding radiotherapy to mMCC patients with limited progression on avelumab seems to be safe and effective in prolonging the successful use of immunotherapy, regardless of the type of immune refractoriness. [ABSTRACT FROM AUTHOR]

Tanju Berber,1 Abdullah Sakin2 1Department of Radiation Oncology, Okmeydani Training and Research Hospital, Istanbul, Turkey; 2Department of Medical Oncology, Medipol University, Bahçelievler Medipol Hospital, Istanbul, TurkeyCorrespondence: Tanju Berber, Department of Radiation Oncology, Okmeydani Training and Research Hospital, Istanbul, 34307, Turkey, Tel +0905324111202, Email tanjuberber@hotmail.comAim: To extend the survival of patients by providing local control of metastases in oligoresistance/oligoprogressive disease.Methods: We retrospectively evaluated the efficacy of stereotactic body radiotherapy (SBRT) applied to 30 lesions in the lungs of 19 patients who were considered inoperable by the tumor board upon the development of oligoresistance/oligoprogressive lung metastasis while undergoing chemotherapy between January 2016 and December 2017. Each patient had one to five metastases in their lungs. The median SBRT biologic effective dose at α/β of 10 (BED10) was 180.0 (IQR: 115.5– 180.0) Gy.Results: We obtained effective, low-toxicity results. The rates of local control were 89.4%, 84.2%, and 78.9% for the 1st, 2nd, and 3rd years, respectively. The median local control time was 4 (IQR: 3– 6) months. The median overall survival (OS) was 36.3 (IQR: 29.7– 42.9) months. The rates of OS for the 1st, 2nd, and 3rd years were 89.5%, 73.7%, and 61.4%, respectively. Despite the nonoccurrence of grade 4– 5 toxicity in the lungs, six (31.6%) patients had grade 1– 3 pulmonary pneumonia, one patient had a grade 4 skin ulceration, and two patients had increased chronic obstructive pulmonary disease in the follow-up period.Discussion: In patients with oligometastatic lung tumors, SBRT is very effective in terms of progression-free survival and OS.Keywords: lung metastasis, stereotactic body radiation therapy, stereotactic ablative radiotherapy, oligometastatic, oligoprogressive, oligoresistance, pallation

Renal cell carcinoma (RCC) is the most common type of kidney cancer, accounting for most renal cancers. Oligoprogressive RCC (OP-RCC) describes metastatic RCC wherein one or a few metastatic sites continue to progress, while the majority of metastatic sites are stable on systemic therapy. Treatment options for the primary site for OP-RCC include cytoreductive nephrectomy, stereotactic body radiation therapy (SBRT), or ablative techniques, although there is no currently agreed-upon standard for treatment. This report describes a 76-year-old male with OP-RCC who was treated with salvage SBRT after failing cytoablation therapy. A review of the current literature on SBRT as a treatment option for OP-RCC is presented and discussed. This case demonstrates that SBRT may be a viable salvage treatment option for patients with OP-RCC that provides good local disease control while preserving long-term renal function., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Heger et al.)

Objectives: stereotactic body radiation therapy (SBRT) use has increased overtime for the management of metastatic renal cell carcinoma (mRCC) patients, with a likely good control of irradiated lesions. We planned a retrospective multicenter Italian study, with the aim of investigating the outcome of treatment with SBRT for non-brain secondary lesions in mRCC patients. Methods: all consecutive metastatic non-brain lesions from mRCC that underwent SBRT at nine Italian institutions from January 2015 to June 2017 were considered. The primary endpoint of the study was the lesion-PFS, calculated from SBRT initiation to the local progression of the irradiated lesion. Results: 57 extracranial metastatic lesions from 48 patients with primary mRCC were treated with SBRT. At the median follow-up of 26.4 months, the median lesion-PFS was not reached (43 censored); 72.4% of lesions were progression-free at 40 months, with significantly better lesion-PFS for small metastatic lesions (

Patrick J Richard, Ramesh Rengan Department of Radiation Oncology, University of Washington, Seattle, WA, USA Abstract: The oligometastatic disease theory was initially described in 1995 by Hellman and Weichselbaum. Since then, much work has been performed to investigate its existence in many solid tumors. This has led to subclassifications of stage IV cancer, which could redefine our treatment approaches and the therapeutic outcomes for this historically “incurable” entity. With a high incidence of stage IV disease, non-small-cell lung cancer (NSCLC) remains a difficult cancer to treat and cure. Recent work has proven the existence of an oligometastatic state in NSCLC in terms of properly selecting patients who may benefit from aggressive therapy and experience long-term overall survival. This review discusses the current treatment approaches used in oligometastatic NSCLC and provides the evidence and rationale for each approach. The prognostic factors of many trials are discussed, which can be used to properly select patients for aggressive treatment regimens. Future advances in both molecular profiling of NSCLC to find targetable mutations and investigating patient selection may increase the number of patients diagnosed with oligometastatic NSCLC. As this disease entity increases, it is of utmost importance for oncologists treating NSCLC to be aware of the current treatment strategies that exist and the potential advantages/disadvantages of each. Keywords: oligometastatic, non-small-cell lung cancer, oligoprogressive, treatment

Objectives: stereotactic body radiation therapy (SBRT) use has increased overtime for the management of metastatic renal cell carcinoma (mRCC) patients, with a likely good control of irradiated lesions. We planned a retrospective multicenter Italian study, with the aim of investigating the outcome of treatment with SBRT for non-brain secondary lesions in mRCC patients., Methods: all consecutive metastatic non-brain lesions from mRCC that underwent SBRT at nine Italian institutions from January 2015 to June 2017 were considered. The primary endpoint of the study was the lesion-PFS, calculated from SBRT initiation to the local progression of the irradiated lesion., Results: 57 extracranial metastatic lesions from 48 patients with primary mRCC were treated with SBRT. At the median follow-up of 26.4 months, the median lesion-PFS was not reached (43 censored); 72.4% of lesions were progression-free at 40 months, with significantly better lesion-PFS for small metastatic lesions (<14 mm). SBRT was safe and the 1-year local disease control was 87.7%. After SBRT, 18 patients (37.5%) permanently interrupted systemic therapy., Conclusions: consistently with the previous literature, our findings support the use of SBRT in selected mRCC patients., Competing Interests: Declaration of Competing Interest M. Bersanelli received research funding from Seqirus, Pfizer, Bristol-Myers Squibb (BMS) and Novartis and honoraria for advisory role and as speaker at scientific events from BMS, Novartis, Pierre-Fabre and Pfizer. S. Buti received research funding from Novartis and honoraria for advisory role and as speaker at scientific events from Pfizer, BMS, IPSEN, Pierre-Fabre, Merck Sharp & Dohme (MSD), AstraZeneca. G. Procopio received honoraria for advisory role from Bayer, BMS, Ipsen, MSD, Novartis, Pfizer. All other authors declared no conflict of interest., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Stage IV non-small cell lung cancer (NSCLC) exists on a spectrum, with a subset of patients presenting with oligometastatic disease involving only a limited number of distant sites. For these patients, local consolidative therapy (LCT) has been demonstrated to improve outcomes through ablation or cytoreduction of metastatic disease, as shown in an increasing number of randomized controlled trials. In particular, stereotactic ablative body radiation (SABR) has emerged as a feasible treatment modality for elimination of oligometastatic sites. This focused review examines the underlying biologic mechanisms and clinical data in support of SABR in the setting of oligometastatic NSCLC. Following a comprehensive evaluation of the pertinent retrospective, prospective, and anticipated trials to date, we summarize the evidence regarding patient selection, treatment safety, and technical considerations to provide guidance of this approach for clinicians., Competing Interests: Conflicts of Interest: Note that portions of this review have been previously published in the textbook Adult Chest Surgery, 3rd Edition, “The Role of Surgery in Oligometastatic Disease.”

Oligometastatic disease is defined as an intermediate state between localized and widespread metastatic disease. Given that in the oligometastatic state gross tumors represent the full extent of disease, there may be a role for curative local therapy despite metastatic disease. As nearly 60% of patients with non-small cell lung cancer (NSCLC) present with metastatic disease and another 45% of patients with initially localized disease will ultimately develop distant metastases, NSCLC represents a prime disease for aggressive intervention. In this review, the definition, prognostic factors, patient selection, rationale and evidence for treatment of oligoprogressive and oligometastatic NSCLC is discussed, including recent prospective trials and future directions., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.