Whether Primary Bone-Only Oligometastatic Nasopharyngeal Carcinoma Patients Benefit From Radiotherapy to the Bones on the Basis of Palliative Chemotherapy Plus Locoregional Radiotherapy?-A Large-Cohort Retrospective Study.

OBJECTIVES: Whether to perform local radiotherapy on metastatic bone for primary bone-only oligometastatic nasopharyngeal carcinoma (NPC) patients remains unclear. Therefore, we analyzed the treatment methods and their survival and developed a prognostic model to predict outcomes and guide personalized treatment. MATERIALS AND METHODS: We studied 308 primary bone-only oligometastatic NPC patients who were treated with either palliative chemotherapy (PCT) alone, PCT combined with locoregional radiotherapy (LRRT), or PCT, LRRT, and radiotherapy to metastatic bones (bRT). The primary endpoint was overall survival (OS). Cox regression was utilized to identify independent prognostic factors, leading to the construction of a nomogram model. Patients were stratified into two risk groups based on median prognostic scores, and treatment modalities were compared using log-rank test while employing the inverse probability of treatment weighting (IPTW) to balance baseline characteristics and adjust for sample size differences between risk groups. RESULTS: The best OS was observed in the group treated with PCT, LRRT, and bRT (HR = 0.60, 95% CI: 0.45-0.81, p = 0.002). Multivariable analysis revealed that age, N stage, pre-treatment levels of LDH, and EBV DNA were independent prognostic factors for OS. In total, 155 patients were in low-risk group while 153 were in high-risk group. Before and after IPTW, the high-risk group benefited from the PCT, LRRT, and bRT regimen (adjusted HR = 0.53, 95% CI: 0.42-0.67, p < 0.001; unadjusted HR = 0.59, 95% CI: 0.42-0.83, p = 0.007), while the low-risk group did not (adjusted HR = 0.79, 95% CI: 0.56-1.11, p = 0.345; unadjusted HR = 0.65, 95% CI: 0.37-1.14, p = 0.309). CONCLUSION: Best outcomes of the whole cohort were seen with PCT + LRRT + bRT. Our study identified age, N stage, pre-treatment LDH levels, and EBV DNA levels as independent prognostic factors for OS. The high-risk group demonstrated a longer OS when treated with PCT + LRRT + bRT, whereas the low-risk group did not benefit from the combinatorial treatment.

Stereotactic Ablative Radiotherapy for Oligometastatic Pericolonic Soft Tissue Metastases Using Daily Cone-Beam Computed Tomography-Guided Online Adaptive Radiotherapy.

A 74-year-old woman with pathologic T4a N1 M0 adenocarcinoma of the cecum, initially treated with right hemicolectomy, developed rising serum carcinoembryonic antigen levels while receiving adjuvant chemotherapy. Re-staging investigations demonstrated two soft tissue metastases in the right abdomen comprised of a retrocolic lesion immediately posterior to the colon and a retroperitoneal lesion with no other sites of metastases. The patient was treated with stereotactic ablative radiotherapy (SABR) to a dose of 40 Gy in five daily fractions to both pericolonic soft tissue metastases simultaneously. A standard volumetric modulated arc therapy (VMAT) plan had suboptimal dose coverage of the retrocolic metastasis adjacent to the colon, so cone-beam computed tomography (CBCT)-guided online adaptive radiotherapy (ART) was employed to maximize radiation dose to the tumors due to the radioresistant histology. An intensity-modulated radiotherapy (IMRT) plan was created using artificial intelligence tools integrated with the treatment unit. Median contouring and plan creation for each fraction was 21.5 minutes (range 14.9-28.1). For the retrocolic metastasis, compared to the standard VMAT plan, the CBCT-guided online ART plan improved coverage of the gross target volume by the prescription dose from 80.0% to 99.7%. SABR to pericolonic soft tissue metastases was feasible using CBCT-guided online ART and can significantly improve target volume coverage when targets are adjacent to mobile normal organs, which may be particularly important for radioresistant histologies for local control.

Stereotactic Body Radiotherapy for Renal Cell Carcinoma-A Review of Use in the Primary, Cytoreductive and Oligometastatic Settings.

Renal cell carcinoma (RCC) has been increasing in incidence by around 1.5% per year for several years. However, the mortality rate has been decreasing by 1.6% per year, and this can be attributed to stage migration and improvements in treatment. One treatment modality that has emerged in recent years is stereotactic body radiotherapy (SBRT), which is an advanced radiotherapy technique that allows the delivery of high-dose radiation to the tumor while minimizing doses to the organs at risk. SBRT has developed a role in the treatment of early-stage, oligometastatic and oligoprogressive RCC. In localized disease, phase II trials and meta-analyses have shown that SBRT provides a very high probability of long-term local control with a low risk of severe late toxicity. In oligometastatic (OMD) RCC, the same level of evidence has similarly shown good local control and minimal toxicity. SBRT could also delay the necessity to start or switch systemic treatments. Medical societies have started to incorporate SBRT in their guidelines in the treatment of localized disease and OMD. A possible future role of SBRT involves cytoreduction. It is theorized that SBRT can lower tumor burden and enhance immune-related response, but it cannot be recommended until the results of the phase II trials are published.

Outcomes and failure patterns after chemoradiotherapy for locally advanced rectal cancer with positive lateral pelvic lymph nodes: a propensity score-matched analysis.

PURPOSE: This study aimed to use propensity score matching (PSM) to explore the long-term outcomes and failure patterns in locally advanced rectal cancer (LARC) patients with positive versus negative lateral pelvic lymph node (LPLN). MATERIALS AND METHODS: Patients with LARC were retrospectively divided into LPLN-positive and LPLN-negative groups. Clinical characteristics were compared between the groups using the chi-square test. PSM was applied to balance these differences. Progression-free survival (PFS) and overall survival (OS), and local-regional recurrence (LRR) and distant metastasis (DM) rates were compared between the groups using the Kaplan-Meier method and log-rank tests. RESULTS: A total of 651 LARC patients were included, 160 (24.6%) of whom had positive LPLN and 491 (75.4%) had negative LPLN. Before PSM, the LPLN-positive group had higher rates of lower location (53.1% vs. 43.0%, P = 0.025), T4 stage (37.5% vs. 23.2%, P = 0.002), mesorectal fascia (MRF)-positive (53.9% vs. 35.4%, P < 0.001) and extramural venous invasion (EMVI)-positive (51.2% vs. 27.2%, P < 0.001) disease than the LPLN-negative group. After PSM, there were 114 patients for each group along with the balanced clinical factors, and both groups had comparable surgery, pathologic complete response (pCR), and ypN stage rates. The median follow-up was 45.9 months, 3-year OS (88.3% vs. 92.1%, P = 0.276) and LRR (5.7% vs. 2.8%, P = 0.172) rates were comparable between LPLN-positive and LPLN-negative groups. Meanwhile, despite no statistical difference, 3-year PFS (78.8% vs. 85.9%, P = 0.065) and DM (20.4% vs. 13.3%, P = 0.061) rates slightly differed between the groups. 45 patients were diagnosed with DM, 11 (39.3%) LPLN-positive and 3 (17.6%) LPLN-negative patients were diagnosed with oligometastases (P = 0.109). CONCLUSIONS: Our study indicates that for LPLN-positive patients, there is a tendency of worse PFS and DM than LPLN-negative patients, and for this group patients, large samples are needed to further confirm our conclusion.

A Case Report of Long-Term Survival Achieved by Nivolumab and Hyperthermia With Multiple Local Therapies for the Peritoneal Dissemination of Gastric Cancer.

A 60-year-old male with recurrent metastatic gastric cancer achieved long-term survival with nivolumab, hyperthermia, and local multisite therapy. The patient had a history of multiple relapses despite receiving standard treatment. After the failure of multiple lines of chemotherapy, nivolumab and hyperthermia were initiated. During this combination therapy, local treatments including surgery and radiation therapy were administered to treat the progressive disease. Remarkably, the patient achieved more than five years of overall survival time after starting nivolumab and external repeated hyperthermia with local therapies and has shown no measurable disease on imaging for the past 24 months. This case suggests that a combination of nivolumab, hyperthermia, and local therapies may offer a potential therapeutic strategy for patients with advanced gastric cancer.

Single-Isocenter, Multiple-Target Abdominal Cone-Beam Computed Tomography (CBCT)-Guided Online Adaptive Stereotactic Body Radiotherapy (SBRT).

Stereotactic body radiotherapy (SBRT) is increasingly being prescribed for treating patients with multiple metastases, especially in the setting of oligometastatic disease. Treating multiple targets presents unique challenges in radiotherapy planning and delivery, including practical considerations relating to treatment time, resource allocation, and treatment planning complexity. Treating targets in a common isocenter reduces the time required for treatment and simplifies planning, but historically, it has often not been feasible due to inter- and intra-fractional variation in relative target positions. With online adaptation, individual targets can be re-contoured on each treatment fraction to obviate inter-fractional variation, and with appropriate margin selection intra-fractional motion can be managed. In this case report, we describe single-isocenter, multiple-target treatment via online adaptation of a 93-year-old man with a history of metastatic hepatocellular carcinoma. He initially presented with a 9.1 cm liver mass, suspicious lung lesions, and an enlarged porta hepatis lymph node, which were biopsy proven to be hepatocellular carcinoma. Following 18 months of systemic immunotherapy, he demonstrated a favorable response, including a reduction in primary liver mass to 5.1 cm and resolution of pulmonary lesions; however, recent serial imaging demonstrated oligoprogression of two peripancreatic lymph node conglomerates that were biopsy proven to be poorly differentiated carcinoma. The patient was offered adaptive SBRT to a dose of 35-40 Gy in five fractions as a consolidative approach for treating both the primary liver mass and oligoprogressive lymph nodes. He tolerated treatment without any grade 2 or higher acute toxicity and had stable disease on three-month post-treatment imaging. By leveraging online adaptation, especially for the daily re-definition of target volumes, we were able to treat three targets in the abdomen accurately in a common isocenter. Treating in this manner vastly shortened and simplified the patient's radiation course. Quantitative evaluation of re-contoured targets and post-treatment imaging highlighted the value of online adaption with careful margin specification and alignment instructions.

Predictive Value of the Prostate-specific Antigen Doubling Time for the Effectiveness of Metastasis-directed Radiotherapy in Patients With Oligometastases After Radical Treatment for Non-metastatic Prostate Cancer.

Background/Aim: Data on metastasis-directed radiotherapy (MDRT) are limited, particularly regarding its association with the prostate-specific antigen (PSA) doubling time (PSADT). The present study evaluated the oncological outcomes of MDRT on the basis of the PSADT in oligo-recurrent prostate cancer patients. Patients and Methods: We retrospectively reviewed clinical data of 35 MDRTs for 29 patients at the Kitasato University Hospital, targeting oligometastatic prostate cancer developed after radical treatment for non-metastatic prostate cancer. Thirty-five MDRTs were classified into the PSADT >3 months (n=25) or PSADT ≤3 months group (n=10). Statistical analyses were performed to compare associations between the two PSADT groups and oncological outcomes such as progression-free survival (PFS) and PSA response after MDRT. Results: There were no significant differences between the two groups in terms of the clinicopathological features. Kaplan-Meier analysis showed that PFS was significantly better in the PSADT >3 months group than in the PSADT ≤3 months group [median: 13.3 versus (vs.) 2.6 months, p=0.046]. Regarding castration sensitivity, the predictive role of PSADT >3 months was maintained in 21 patients who received MDRT without prior salvage hormone therapy (median PFS: 12.7 vs. 2.6 months, p=0.024). In the castration-resistant setting (n=14), the frequency of a decrease in serum PSA levels after MDRT by 90% was 54.5% (median PFS: 23.1 months). Conclusion: MDRT can provide benefit especially for patients with PSADT ≥3 months who had oligo-recurrence after the radical treatment for non-metastatic prostate cancer.

Stereotactic body radiation therapy in non-liver colorectal metastases: a scoping review.

Background: In oligometastatic colorectal cancer (CRC), stereotactic body radiation therapy (SBRT) represents a valid non-invasive local ablative treatment with high rates of local control (LC) and a low toxicity profile. This literature review was performed to evaluate the clinical benefit and toxicity of SBRT on non-liver metastases in CRC oligometastatic patients. Methods: After searching PubMed, Medscape and Embase databases, 18 retrospective studies focused on body oligometastases excluding bone metastases were included in the analysis. Results: A total of 1,450 patients with 3,227 lung metastases and 53 patients with 66 nodes lesions were analyzed. BED10 ranged from 76 to 180 Gy. In the lung group, the LC rate was 62-91%, 54-81% and 56-77% after 1, 3 and 5 years, respectively. In the nodes group, the 3-year LC rate was 65-75%. The 1-, 3- and 5-year OS rates were 73-100%, 51-64% and 34-43%, respectively for the lung group, and 63-81% at 3 years for the nodes group. Conclusions: In CRC patients with non-liver oligometastases, the use of SBRT is effective and safe reaching high LC and survival, with few severe side effects. However, prospective randomized studies are needed to validate the results. These studies will also be useful for identifying any predictive factors that allow us to select the subgroup of patients who benefit from SBRT.

Automated single-isocenter stereotactic body radiotherapy for multiple metastases from breast cancer: A case study.

Oligometastatic breast cancer patients can today could benefit from a multimodal approach, combining systemic therapy with metastasis-directed treatment using stereotactic body radiotherapy (SBRT). However, the possibility to synchronously treat multiple lesions is still challenging, needing the ability to generate complex dose distributions with steep dose gradients outside the lesions and major sparing of surrounding organs at risk and accurately track and reproduce the patient's position before and during radiation therapy. We report the case of an oligometastatic patient from left breast cancer, which occurred after a full course of whole breast radiotherapy, treated using the potential of modern technology including single-isocenter setup, plan automation, breath-hold technique and surface guided tracking and reproducibility of patient's position before and during radiation therapy. A 44-year-old female patient with a history of left breast cancer, specifically a luminal-B-like invasive ductal carcinoma with Her2 overexpression, was admitted to our department. The patient previously underwent a left mastectomy (pT2N0M0), 4 cycles of adjuvant chemotherapy, adjuvant radiotherapy on the chest wall and lymph nodes drainage, and 5 years of hormonal therapy. A chest wall ultrasound and positron emission tomography revealed the presence of new lesions in the area of the surgical scar from the previous mastectomy, internal mammary, axillary and retropectoral levels. The 3 lesions were simultaneously treated with a mono-isocentric VMAT plan using SBRT technique with a total dose of 30 Gy delivered in 5 fractions. Due to the technical challenges, this treatment was supported by the use of planning automation, breath-hold technique and surface-guided radiation therapy to improve the accuracy of the dose delivery. Two different plans were generated and compared to pursue the best dosimetric result, including a summed plan obtained from 3 individual SBRT plans for each lesion with a separate isocenter placed in each of them (MIP), and a single-isocenter SBRT plan able to treat multiple lesions synchronously (SIP). Because of the advantages in terms of dosimetry and dose delivery efficiency, the patient was successfully treated with the SIP plan. The treatment time was reduced to about 4.5 minutes, allowing the comfortably use of breath-hold technique. After treatment, the condition of the patient was normal, and no toxicities have been observed in follow-up. SBRT with mono isocentric VMAT planning represents the recommended approach to simultaneously treat multiple lesions in close proximity in the thoracic district.

MCT4 is an independent prognostic factor and affects immune cell infiltration in patients with colorectal liver oligometastases.

BACKGROUND: Monocarboxylate transporter 4 (MCT4) is a novel biomarker related to the level of immune cell infiltration, but its impact on tumor immune microenvironment (TIME) of colorectal liver oligometastases (CLO) remains unclear. The aim of this study was to assess MCT4 expression in primary tumor and liver oligometastases, investigate its impact on immune cell infiltration and its prognostic value for CLO patients undergoing liver resection. METHODS: We retrospectively selected 135 CLO patients who underwent curative liver resection between June 1999 and December 2016, and samples included 74 primary tumor tissues and 122 liver metastases. Immunohistochemistry (IHC) was performed to detect MCT4 expression in paraffin-embedded specimens and tyramine signal amplification (TSA) was used to detect the density of tumor-infiltrating lymphocytes, including CD3 + , CD8 + and Foxp3 + . Recurrence-free survival (RFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and log-rank test, and independent prognostic factors were identified with Cox regression modeling. RESULTS: Survival analysis indicated that CLO patients with low MCT4 expression had better 3-year RFS and 3-year OS rates than those with high MCT4 expression. Multivariate analysis indicated that high MCT4 expression was independently associated with poor RFS and OS. High MCT4 expression was associated with a lower number of intratumoral CD3 + /CD8 + T cells and was associated with higher Foxp3 + T cells infiltration. Patients with low MCT4 expression and high levels of differential immune infiltration had longer survival. CONCLUSIONS: MCT4 overexpression was associated with an unfavorable prognosis in patients with CLO and MCT4 expression level had an impact on intratumoral immune infiltration degree. A novel parameter that combined MCT4 expression level and differential immune infiltration level was constructed to stratify patients with CLO into different risk groups.

Oligometastatic Urothelial Cancer and Stereotactic Body Radiotherapy: A Systematic Review and an Updated Insight of Current Evidence and Future Directions.

BACKGROUND: Stereotactic body radiation therapy (SBRT) is the most commonly used metastasis-directed therapy (MDT) for oligometastatic urothelial carcinoma (omUC). Despite efforts in defining this disease entity, open questions remain concerning the role of MDT and the use of biomarkers, imaging, and its combination with systemic therapies. The aim of the present systematic review is to provide an updated overview of the current clinical evidence on SBRT for omUC in terms of survival and local control benefits. We also aim to provide updates on controversial areas and future directions in this emerging field. METHODS: With a systematic approach, following PRISMA recommendations, we searched two databases to identify and select articles published up until March 2024 reporting the use of SBRT for omUC with or without concomitant systemic therapies. Prospective randomized or non-randomized studies as well as retrospective studies were included. RESULTS: Eight studies were selected for data extraction and 293 omUC patients treated with SBRT were collectively analyzed. In metachronous omUC patients, SBRT delivered with ablative doses (BED10 ≥ 78 Gy) was associated with a 2-year overall survival (OS) rate of 50.7% (95% CI 35.1-64.4%). The use of sub-ablative SBRT doses (BED10 = 43.2 Gy) in combination with immunotherapy did not demonstrate significant clinical outcome improvement in two prospective studies. The overall tolerance was good, with only one study reporting toxicity of grade 3 in up to 18% of the patients treated with SBRT in combination with immunotherapy. CONCLUSIONS: SBRT is an effective and widely available MDT option in omUC, although this is based on a limited number of studies. Despite the attempt to use SBRT as an immune response trigger in combination with immunotherapy, no significant improvement in survival outcomes has been observed. The integration of new systemic agents with MDT will likely define a new scenario for the treatment of omUC. The review protocol was registered in PROSPERO, ID: CRD42024522381.

A randomized phase III trial of stereotactic ablative radiotherapy for patients with up to 10 oligometastases and a synchronous primary tumor (SABR-SYNC): study protocol.

BACKGROUND: Emerging randomized data, mostly from phase II trials, have suggested that patients with oligometastatic cancers may benefit from ablative treatments such as stereotactic ablative radiotherapy (SABR). However, phase III data testing this paradigm are lacking, and many studies have examined SABR in the setting of metachronous oligometastatic disease. The goal of the SABR-SYNC trial is to assess the effect of SABR in patients with oligometastatic cancers and a synchronous primary tumor. METHODS: One hundred and eighty patients will be randomized in a 1:2 ratio between standard of care (SOC) palliative-intent treatments vs. SOC + ablative therapy (SABR preferred) to all sites of known disease. Randomization will be stratified based on histology and number of metastases at enrollment. SABR may be delivered in 1-, 3- and 5-fraction regimens, with recommended doses of 20 Gy, 30 Gy, and 35 Gy, respectively. Non-SABR local modalities (e.g. surgery, thermal ablation, conventional radiation) may be used for treatment of the primary or metastases at the discretion of the treating physicians, if those modalities are clinically preferred. The primary endpoint is overall survival, and secondary endpoints include progression-free survival, time to development of new metastatic lesions, time to initiation of next systemic therapy, quality of life, and toxicity. Translational endpoints include assessment of circulating tumor DNA and immunological predictors of outcomes. DISCUSSION: SABR-SYNC will provide phase III data to assess the impact of SABR on overall survival in a population of patients with synchronous oligometastases. The translational component will attempt to identify novel prognostic and predictive biomarkers to aid in clinical decision making. TRIAL REGISTRATION: Clinicaltrials.gov NCT05717166 (registration date: Feb. 8, 2023).

Efficacy and prognostic factors of stereotactic body radiotherapy combined with immunotherapy for pulmonary oligometastases: a preliminary retrospective cohort study.

Background: Stereotactic body radiotherapy (SBRT) combined immunotherapy has a synergistic effect on patients with stage IV tumors. However, the efficacy and prognostic factors analysis of SBRT combined immunotherapy for patients with pulmonary oligometastases have rarely been reported in the studies. The purpose of this study is to explore the efficacy and prognostic factors analysis of SBRT combined immunotherapy for patients with oligometastatic lung tumors. Methods: A retrospective analysis was conducted on 43 patients with advanced tumors who received SBRT combined with immunotherapy for pulmonary oligometastases from October 2018 to October 2021. Local control (LC), progression-free survival (PFS), and overall survival (OS) were assessed using the Kaplan-Meier method. Univariate and multivariate analyses of OS were performed using the Cox regression model, and the P value <0.05 was considered statistically significant. The receiver operating characteristic (ROC) curve of neutrophil-to-lymphocyte ratio (NLR) after SBRT was generated. Spearman correlation analysis was used to determine the relationship of planning target volume (PTV) with absolute lymphocyte count (ALC) before and after SBRT and with neutrophil count (NE) after SBRT. Additionally, linear regression was used to examine the relationship between ALC after SBRT and clinical factors. Results: A total of 43 patients with pulmonary oligometastases receiving SBRT combined with immunotherapy were included in the study. The change in NLR after SBRT was statistically significant (P<0.001). At 1 and 2 years, respectively, the LC rates were 90.3% and 87.5%, the OS rates were 83.46% and 60.99%, and the PFS rates were 69.92% and 54.25%, with a median PFS of 27.00 (17.84-36.13) months. Univariate and multivariate Cox regression analyses showed that a shorter interval between radiotherapy and immunization [≤21 days; hazard ratio (HR) =1.10, 95% confidence interval (CI): 0.06-0.89; P=0.02] and a low NLR after SBRT (HR =0.24, 95% CI: 1.01-1.9; P=0.03) were associated with improved OS. The ROC curve identified 4.12 as the cutoff value for predicting OS based on NLR after SBRT. NLR after SBRT ≤4.12 significantly extended OS compared to NLR after SBRT >4.12 (log-rank P=0.001). Spearman correlation analysis and linear regression analysis showed that PTV was negatively correlated with ALC after SBRT. Conclusions: Our preliminary research shows that SBRT combined with immunotherapy has a good effect, and NLR after SBRT is a poor prognostic factor for OS. Larger PTV volume is associated with decreased ALC after SBRT.

Stereotactic body radiotherapy for spinal oligometastases: a survey on patterns of practice on behalf of the Italian Association of Clinical Oncology and Radiotherapy (AIRO).

BACKGROUND: The Study Group for the Biology and Treatment of the OligoMetastatic Disease on behalf of the Italian Association of Radiotherapy and Clinical Oncology (AIRO) has conducted a national survey with the aim to depict the current patterns of practice of stereotactic body radiotherapy (SBRT) for spinal oligometastases. METHODS: The Surveymonkey platform was used to send a 28-items questionnaire focused on demographic, clinical and technical aspects related to SBRT for spinal oligometastases. All the AIRO members were invited to fill the questionnaire. Data were then centralized to a single center for analysis and interpretation. RESULTS: 53 radiation oncologists from 47 centers fulfilled the survey. A complete agreement was observed in proposing SBRT for spinal oligometastases, with the majority considering up to 3 concurrent spine oligometastases feasible for SBRT (73.5%), regardless of spine site (70%), vertebral segment (85%) and morphological features of the lesion (71.7%). Regarding dose prescription, fractionated regimens resulted as the preferred option, either in 3 (58.4%) or five sessions (34%), with a substantial agreement in applying a PTV-margin larger than 1 mm (almost 90% of participants), and ideally using both MRI and PET imaging to improve target volume and organs-at-risk delineation (67.9%). CONCLUSIONS: This national italian survey illustrates the patterns of practice and the main issues for the indication of SBRT for spinal oligometastases. A substantial agreement in the numerical cut-off and vertebral segment involved for SBRT indication was reported, with a slight heterogeneity in terms of dose prescription and fractionation schemes.

Acute toxicity in patients with oligometastatic cancer following metastasis-directed stereotactic body radiotherapy: An interim analysis of the E2-RADIatE OligoCare cohort.

AIM: To evaluate acute toxicity at 6 months after stereotactic body radiotherapy (SBRT) in patients with oligometastatic cancer within the OligoCare cohort. MATERIAL AND METHODS: OligoCare is a prospective, registry-based, single-arm, observational study that aims to report prospective real-world data of patients with oligometastases from solid cancer treated with SBRT (NCT03818503). Primary tumor included non-small cell lung cancer (NSCLC), breast cancer (BC), colorectal cancer (CRC), and prostate cancer (PC). This analysis addresses a secondary endpoint of the trial, acute toxicity within 6 months after SBRT. RESULTS: Out of 1,597registered patients, 1'468 patients were evaluated for acute toxicity. Globally, 290 (20 %) had NSCLC primary disease, 227 (16 %) had BC, 293 (20 %) had CRC, and 658 (45 %) had PC. Concomitant systemic treatment was administered in 527 (35.9 %) patients. According to the EORTC/ESTRO oligometastatic disease (OMD) classification, 828 (56 %) patients had de novo OMD, 464 (32 %) repeat OMD, and 176 (12 %) induced OMD. Acute grade ≥ 3 SBRT related adverse events were reported in 8 (0.5 %) patients, including 2 (0.1 %) fatal AEs. In particular, 6 (0.4 %) grade 3 events were: 1 empyema, 1 pneumonia, 1 radiation pneumonitis, 1 radiation skin injury, 1 decreased appetite, and 1 bone pain. Among those 2 occurred in NSCLC patients, 2 in BC patients, and 1 in CRC and PC patients each. The two (0.1 %) grade 5 toxicity were represented by: pneumonitis and cerebral hemorrhage. CONCLUSION: OligoCare is the largest prospective registry cohort on oligometastatic disease. Acute toxicity within 6 months was low, confirming the safety of SBRT in the treatment of oligometastases.

A novel prognostic score (HAMP) for head and neck cancer patients with single and multiple SBRT-treated lung metastases derived from retrospective analyses of survival outcome.

BACKGROUND: We report on the characterization and introduction of a novel prognostic score for patients undergoing stereotactic body radiotherapy (SBRT) for the treatment of single and multiple pulmonary metastases (PMs) derived from head and neck cancer (HNC). METHODS: In this retrospective study, we examined selected factors associated with progression-free survival (PFS) and overall survival (OS) among 59 patients with HNC treated with SBRT for a total of 118 PMs, between 2009 and 2023. Factors related to survival were included in the prognostic scoring system. RESULTS: Prognostic factors including histology, age, number of metastases, and performance status at first SBRT were weighted differently depending on the strength of correlation to PFS and OS. Total prognostic scores (HAMP) ranged from 13 to 24 points, with a cut-off total score of ≤18 scoring points for patients in a high-risk (HR) subcohort, and of ≥19 scoring points for patients in a low-risk group (LR). Median PFS (23.8 vs. 5.5 months, p < 0.001) and OS (61.3 vs. 16.4 months, p < 0.001) were significantly longer in the low-risk group compared to the high-risk group. CONCLUSION: The HAMP score might be a convenient tool to facilitate individualized treatment decisions and appropriate follow-up. The accuracy and reliability of the score requires further evaluation in prospective studies.

Stereotactic body radiation therapy for the primary tumor and oligometastases versus the primary tumor alone in patients with metastatic pancreatic cancer.

BACKGROUND: Local therapies may benefit patients with oligometastatic cancer. However, there were limited data about pancreatic cancer. Here, we compared the efficacy and safety of stereotactic body radiation therapy (SBRT) to the primary tumor and all oligometastases with SBRT to the primary tumor alone in patients with metastatic pancreatic cancer. METHODS: A retrospective review of patients with synchronous oligometastatic pancreatic cancer (up to 5 lesions) receiving SBRT to all lesions (including all oligometastases and the primary tumor) were performed. Another comparable group of patients with similar baseline characteristics, including metastatic burden, SBRT doses, and chemotherapy regimens, receiving SBRT to the primary tumor alone were identified. The primary endpoint was overall survival (OS). The secondary endpoints were progression frees survival (PFS), polyprogression free survival (PPFS) and adverse events. RESULTS: There were 59 and 158 patients receiving SBRT to all lesions and to the primary tumor alone. The median OS of patients with SBRT to all lesions and the primary tumor alone was 10.9 months (95% CI 10.2-11.6 months) and 9.3 months (95% CI 8.8-9.8 months) (P < 0.001). The median PFS of two groups was 6.5 months (95% CI 5.6-7.4 months) and 4.1 months (95% CI 3.8-4.4 months) (P < 0.001). The median PPFS of two groups was 9.8 months (95% CI 8.9-10.7 months) and 7.8 months (95% CI 7.2-8.4 months) (P < 0.001). Additionally, 14 (23.7%) and 32 (20.2%) patients in two groups had grade 3 or 4 treatment-related toxicity. CONCLUSIONS: SBRT to all oligometastases and the primary tumor in patients with pancreatic cancer may improve survival, which needs prospective verification.

The Landscape of Stereotactic Ablative Radiotherapy (SABR) for Renal Cell Cancer (RCC).

Renal cell cancer (RCC) has traditionally been considered radioresistant. Because of this, conventional radiotherapy (RT) has been predominantly relegated to the palliation of symptomatic metastatic disease. The implementation of stereotactic ablative radiotherapy (SABR) has made it possible to deliver higher ablative doses safely, shifting the renal radioresistance paradigm. SABR has increasingly been adopted into the multidisciplinary framework for the treatment of locally recurrent, oligoprogressive, and oligometastatic disease. Furthermore, there is growing evidence of SABR as a non-invasive definitive therapy in patients with primary RCC who are medically inoperable or who decline surgery, unsuited to invasive ablation (surgery or percutaneous techniques), or at high-risk of requiring post-operative dialysis. Encouraging outcomes have even been reported in cases of solitary kidney or pre-existing chronic disease (poor eGFR), with a high likelihood of preserving renal function. A review of clinical evidence supporting the use of ablative radiotherapy (SABR) in primary, recurrent, and metastatic RCC has been conducted. Given the potential immunogenic effect of the high RT doses, we also explore emerging opportunities to combine SABR with systemic treatments. In addition, we explore future directions and ongoing clinical trials in the evolving landscape of this disease.

Trial Protocol of a Phase II Study of mFOLFOXIRI after Metastasectomy in Patients with Oligometastatic Colorectal Cancer (FANTASTIC Study).

Background: The survival benefit of adjuvant chemotherapy after surgical resection of oligometastases from colorectal cancer (CRC) remains unclear. The prognostic role of circulating-tumor DNA (ctDNA) was reported recently and a risk stratification strategy based on monitoring minimal/molecular residual disease (MRD) has been proposed, however, which drug regimen is most effective for ctDNA-positive patients is unknown. Methods/Design: Oligometastatic CRC patients planning to undergo surgery were registered in this study. After metastasectomy, the registered patients were enrolled in the treatment arm, in which 8 courses of modified-FOLFOXIRI (mFOLFOXIRI; irinotecan 150 mg/m2, oxaliplatin 85 mg/m2, l-leucovorin (l-LV) 200 mg/m2, and 46-h continuous infusion of 5-fluorouracil (5-FU) 2400 mg/m2 every 2 weeks) followed by 4 courses of 5-FU/l-LV are administered. The patients who did not meet the eligibility criteria for the treatment arm or did not consent to mFOLFOXIRI enrolled in the observation arm in which standard of care treatment is provided. Prospective blood collections for retrospective ctDNA analysis are scheduled pre-surgery, and at 28 days, 4 and 7 months after surgery. The primary endpoint is treatment compliance at 8 courses of mFOLFOXIRI and the key secondary endpoints are the ctDNA-positivity rate and survival outcomes in ctDNA-positive and -negative groups. A total of 85 patients will be enrolled from 11 institutions. First patient-in was on July 2020. Accrual completed in February 2024. Discussion: This study will potentially identify a better treatment strategy for patients with resectable oligometastatic CRC having postsurgical ctDNA positivity, compared to the current standard of care approaches.