Local Progression-free Survival Research Articles

MRI- Versus CT-Guided Renal Tumor Cryoablation: Is There a Difference?

To compare procedure-related variables, safety, renal function, and oncologic outcomes in patients undergoing percutaneous cryoablation (CA) of renal tumors with MRI- or CT-guidance. Patient, tumour, procedure, and follow-up data were collected and analysed. MRI and CT groups were matched using a coarsened exact approach according to patient'sgender and age, tumour grade, size and location. P < 0.05 was considered statistically significant. Two-hundred fifty-three patients (266 tumors) were retrospectively selected. Following the coarsened exact matching 46 patients (46 tumors) in the MRI group and 42 patients (42 tumors) in the CT group were matched. There were no significant baseline differences between the two populations except for the duration of follow-up (P = 0.002) and renal function (P = 0.002). On average MRI-guided CA lasted 21min longer than CT-guided ones (P = 0.005). Following CA, complication rates (6.5% for MRI vs 14.3% for CT; P = 0.30) and GFR decline (mean - 13.1 ± 15.8%; range - 64.5-15.0 for MRI; mean - 8.1 ± 14.8%; range - 52.5-20.4; for CT; P = 0.13) were similar in both groups. The 5-year local progression-free, cancer-specific and overall survivals in the MRI and CT groups were 94.0% (95% CI 86.3%-100.0%) and 90.8% (95% CI 81.3%-100.0%; P = 0.55), 100.0% (95% CI 100.0%-100.0%) and 100.0% (95% CI 100.0%-100.0%; P = 1), and 83.7% (95% CI 64.0%-100.0%) and 76.2% (95% CI 62.0%-93.6%; P = 0.41), respectively. Apart from increased procedural times associated with MRI-guided CA of renal tumors compared to CT-guidance, both modalities demonstrate similar safety, GFR decline and oncologic outcomes.

Fractionated stereotactic radiotherapy of brain metastases: results of a retrospective study

BackgroundLasting local control of brain metastases following stereotactic radiotherapy is becoming increasingly relevant since systemic treatment constantly improves the prognosis of patients with extracranial metastases.Methods73 patients with 103 brain metastases received hypofractionated stereotactic radiotherapy (FSRT) in 6 fractions of 5 Gy between January 2017 and December 2021 at the University Hospital Regensburg, Germany. The study retrospectively evaluated local progression free survival (LPFS), overall survival (OS) and distant brain progression free survival (DPFS) of patients without prior radiotherapy of the brain. Response rate and brain radiation necrosis were reported. Cox proportional hazard models evaluated prognostic factors of OS and LPFS.ResultsThe median patient age was 61.0 years (Interquartile range, IQR 51.0, 67.5). The most common tumor types were malignant melanoma (34.2%) and non-small cell lung adenocarcinoma (26.0%). The median gross tumor volume (GTV) was 0.9 cm³ (IQR 0.4, 3.6). The median follow-up time of all patients was 36.3 months (95%CI 29.1, 43.4). The median OS was 17.4 months (95%CI 9.9, 24.9). Overall survival rates at 6-, 12-, 18-, 24-, and 30 months were 81.9%, 59.1%, 49.0%, 41.3%, and 37.2%, retrospectively. The mean LPFS was 38.1 months (95%CI 31.4, 44.9), while the median LPFS has not been reached. LPFS rates at 6-, 12-, 18-, 24- and 30 months were 78.9%, 68.7%, 64.3%, 61.6% and 58.7%, retrospectively. Median DPFS of all patients was 7.7 months (95%CI 6.1, 9.3). Six, 12-, 18-, 24- and 30 months DPFS rates were 62.1%, 36.3%, 31.1%, 24.8% and 21.7%. Five brain metastases (4.8%) developed brain radiation necrosis. In multivariate analysis, the number of brain metastases negatively affected LPFS. Non-melanoma and non-renal cell cancer was associated with a higher chance of LPFS in comparison to other cancer. A GTV > 1.5 cm³ translated into a higher risk of death compared to a GTV ≤ 1.5 cm³ and Karnofsky performance score was predictive of OS.ConclusionsFSRT in 6 fractions of 5 Gy seems to be an effective treatment with an acceptable local control for patients with brain metastases although melanoma and renal cell cancer seem to have a worse local control in comparison to other cancer.Trial registrationThis study is retrospectively registered.

Treatment of spontaneous canine mast cell tumors by electrochemotherapy combined with IL-12 gene electrotransfer: Comparison of intratumoral and peritumoral application of IL-12

The combined treatment of electrochemotherapy (ECT) and interleukin-12 (IL-12) gene electrotransfer (GET) has already been used in clinical studies in dogs to treat various histological types of spontaneous tumors. The results of these studies show that the treatment is safe and effective. However, in these clinical studies, the routes of administration of IL-12 GET were either intratumoral (i.t.) or peritumoral (peri.t.). Therefore, the objective of this clinical trial was to compare the two IL-12 GET routes of administration in combination with ECT and their contribution to the enhanced ECT response. Seventy-seven dogs with spontaneous mast cell tumors (MCTs) were divided into three groups: one treated with a combination of ECT + GET peri. t. (29 dogs), the second with the combination of ECT + GET i.t. (30 dogs), and the third with ECT alone (18 dogs). In addition, immunohistochemical studies of tumor samples before treatment and flow cytometry of peripheral blood mononuclear cells (PBMCs) before and after treatment were performed to determine any immunological aspects of the treatment. The results showed that local tumor control was significantly better in the ECT + GET i.t. group (p < 0.050) than in the ECT + GET peri.t. or ECT groups. In addition, disease-free interval (DFI) and progression-free survival (PFS) were significantly longer in the ECT + GET i.t. group than in the other two groups (p < 0.050). The data on local tumor response, DFI, and PFS were consistent with immunological tests, as we detected an increased percentage of antitumor immune cells in the blood after treatment in the ECT + GET i.t. group, which also indicated the induction of a systemic immune response. In addition, we did not observe any unwanted severe or long-lasting side effects. Finally, due to the more pronounced local response after ECT + GET i.t., we suggest that treatment response assessment should be performed at least two months after treatment, which meets the iRECIST criteria.

Intratumoral injection of oncolytic virus (H101) in combination with concurrent chemoradiotherapy for locally advanced cervical cancer

ObjectivesTo evaluate the efficacy of primary tumor bulk reduction and the safety of concurrent chemoradiotherapy in combination with H101, a type of oncolytic virus, for the treatment of locally advanced...

PSMA-PET/CT-Based Stereotactic Body Radiotherapy (SBRT) in the Treatment of Uncomplicated Non-Spinal Bone Oligometastases from Prostate Cancer

Background and purpose: Stereotactic body radiotherapy (SBRT) has a consolidated role in the treatment of bone oligometastases from prostate cancer (PCa). While the evidence for spinal oligometastases SBRT was robust, its role in non-spinal-bone metastases (NSBM) is not standardized. In fact, there was no clear consensus about dose and target definition in this setting. The aim of our study was to evaluate efficacy, toxicity, and the pattern of relapse in SBRT delivered to NSBM from PCa. Materials and methods: From 2016 to 2021, we treated a series of oligo-NSBM from PCa with 68Ga-PSMA PET/CT-guided SBRT. The primary endpoint was local progression-free survival (LPFS). The secondary endpoints were toxicity, the pattern of intraosseous relapse, distant progression-free survival (DPFS), polimetastases-free survival (PMFS), and overall survival (OS). Results: a total of 150 NSBM in 95 patients were treated with 30–35 Gy in five fractions. With a median follow-up of 26 months, 1- and 3 years LPFS was 96.3% and 89%, respectively. A biologically effective dose (BED) ≥ 198 Gy was correlated with improved LPFS (p = 0.007). Intraosseous relapse occurred in eight (5.3%) cases. Oligorecurrent disease was associated with a better PMFS compared to de novo oligometastatic disease (p = 0.001) and oligoprogressive patients (p = 0.007). No grade ≥ 3 toxicity occurred. Conclusion: SBRT is a safe and effective tool for NSBM from PCa in the oligometastatic setting. Intraosseous relapse was a relatively rare event. Predictive factors of the improved outcomes were defined.

Feasibility of additional radiotherapy in patients with advanced hepatocellular carcinoma treated with atezolizumab plus bevacizumab.

Radiotherapy (RT) is an effective local treatment for hepatocellular carcinoma (HCC). However, whether additional RT is safe and effective in patients with advanced HCC receiving atezolizumab plus bevacizumab remains unclear. This retrospective cohort study aimed to evaluate the feasibility of additional RT in these patients. Between March and October 2021, we retrospectively analyzed seven patients with advanced HCC who received RT during treatment with atezolizumab plus bevacizumab. The median prescribed RT dose was 35 Gy (range, 33-66). Freedom from local progression (FFLP), progression-free survival (PFS), and overall survival (OS) after RT were analyzed. The median follow-up duration after RT was 14.2 months (range, 10.0-18.6). Of the seven patients, disease progression was noted in six (85.7%), the sites of disease progression were local in two (28.6%), intrahepatic in four (57.1%), and extrahepatic in four (57.1%). The median time of FFLP was not reached, and PFS and OS times were 4.0 (95% confidence interval [CI], 3.6-4.5) and 14.8% (95% CI, 12.5-17.2) months, respectively. The 1-year FFLP, PFS, and OS rates were 60% (95% CI, 43.8-76.2), 0%, and 85.7% (95% CI, 75.9-95.5), respectively. Grade 3 or higher hematologic adverse events (AEs) were not observed, but grade 3 nonhematologic AEs unrelated to RT were observed in one patient. The addition of RT may be feasible in patients with advanced HCC treated with atezolizumab plus bevacizumab. However, further studies are required to validate these findings.

Boron Neutron Capture Therapy Followed by Image-Guided Intensity-Modulated Radiotherapy for Locally Recurrent Head and Neck Cancer: A Prospective Phase I/II Trial.

This trial investigated the efficacy and safety of salvage boron neutron capture therapy (BNCT) combined with image-guided intensity-modulated radiotherapy (IG-IMRT) for recurrent head and neck cancer after prior radiotherapy (RT). BNCT was administered using an intravenous boronophenylalanine-fructose complex (500 mg/kg) in a single fraction; multifractionated IG-IMRT was administered 28 days after BNCT. For BNCT, the mucosa served as the dose-limiting organ. For IG-IMRT, the clinical target volume (CTV) and the planning target volume (PTV) were generated according to the post-BNCT gross tumor volume (GTV) with chosen margins. This trial enrolled 14 patients, and 12 patients received combined treatment. The median BNCT average dose for the GTV was 21.6 Gy-Eq, and the median IG-IMRT dose for the PTV was 46.8 Gy/26 fractions. After a median (range) follow-up period of 11.8 (3.6 to 53.2) months, five patients had a complete response and four had a partial response. One patient had grade 4 laryngeal edema; another patient had a grade 4 hemorrhage. Most tumor progression occurred within or adjacent to the CTV. The 1-year overall survival and local progression-free survival rates were 56% and 21%, respectively. Despite the high response rate (64%) of this trial, there was a high incidence of in-field and marginal failure with this approach. Future studies combining BNCT with modalities other than radiation may be tried.

Individualized Concurrent Chemotherapy for Patients with Stage III-IVa Nasopharyngeal Carcinoma Receiving Neoadjuvant Chemotherapy Combined with Definitive Intensity-Modulated Radiotherapy.

This retrospective study aimed to re-evaluate the effect of concurrent chemotherapy in patients with locally advanced nasopharyngeal carcinoma (NPC) in the era of intensity-modulated radiotherapy (IMRT). A total of 498 patients who received neoadjuvant chemotherapy (NCT) combined with concurrent chemoradiotherapy (CCRT) or IMRT were retrospectively reviewed. The distribution of baseline characteristics was balanced using propensity score matching. Additionally, the results of NCT+IMRT and NCT+CCRT were compared using Kaplan-Meier survival analysis, and differences in survival rates were analyzed using the log rank test. There were no significant differences in overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and local progression-free survival (LRFS) between the two groups. Patients were further categorized into risk subgroups based on pretreatment Epstein-Barr virus (EBV) DNA cutoff values using receiver operating characteristic curve analysis. There were no statistically significant differences in OS, PFS, DMFS, and LRFS between patients who received NCT+CCRT and NCT+IMRT in the high-risk group. In the low-risk group, although there were no differences between NCT+CCRT and NCT+IMRT in OS, PFS, and LRFS, patients who received NCT+CCRT had better DMFS than those who received NCT+IMRT. Pretreatment EBV DNA level can be used to individualize concurrent chemotherapy for patients with locally advanced NPC. Patients with low pretreatment EBV DNA levels may benefit from concurrent chemotherapy, whereas those with high levels may not. Other treatment modalities need to be explored for high-risk patients to improve their prognosis.

Role of Surgery in Metastatic Breast Cancer: Insights from a Narrative Review.

Metastatic breast cancer is difficult to cure and has a worse prognosis with higher rates of mortality. Recently, breast surgery is believed to improve the survival rates among these women, but due to limited evidence, definite conclusions cannot be made. Therefore, we undertook this narrative review to synthesize the evidence from existing studies to assess the effectiveness of locoregional surgery and surgery of metastatic sites in improving the outcomes among women diagnosed with metastatic cancer disease along with the summary of current treatment guidelines. We reviewed PubMed and Embase and included both observational studies and randomized controlled trials (RCTs) that were published in English between 2000 and 2021. Outcomes were either survival, quality of life, toxicity related to local treatment assessed by mortality at the end of one month, progression-free survival, and breast cancer-specific survival. The main effect size assessed was hazard ratio with their 95% CIs. After literature search, we found 8 observational studies and 3 RCTs. The findings of the observational studies revealed that breast cancer surgery improves survival from 30% to 50% among women. However, findings from RCTs were mixed for local and distant progression survival. Surgery improved the local progression-free survival but worsened the distant progression-free survival. Besides, there was no effect of breast surgery on quality of life. Regarding the surgery of metastatic site, studies are complex with mixed findings and variation in survival depending upon the type of metastatic site and response to initial systematic therapy and other factors. Based on the existing mixed evidence, it is not possible to make firm and definite conclusions about the effectiveness of breast surgery in improving the survival or quality of life among women with metastatic breast cancer. In future, more RCTs are required with a larger sample size to confirm the findings of observational studies.

Correlations between pathogenic variants in DNA repair genes and anticancer treatment efficacy in stage IV non-small cell lung cancer: A large real-world cohort and review of the literature.

Mutations in genes involved in DNA damage repair (DDR), a hallmark of cancer, are associated with increased cancer cell sensitivity to certain therapies. This study sought to evaluate the association of DDR pathogenic variants with treatment efficacy in patients with advanced non-small cell lung cancer (NSCLC). A retrospective cohort of consecutive patients with advanced NSCLC attending a tertiary medical center who underwent next-generation sequencing in 01/2015-8/2020 were clustered according to DDR gene status and compared for overall response rate (ORR), progression-free survival (PFS) (patients receiving systemic therapy), local PFS (patients receiving definitive radiotherapy), and overall survival (OS) using log-rank and Cox regression analyses. Of 225 patients with a clear tumor status, 42 had a pathogenic/likely pathogenic DDR variant (pDDR), and 183 had no DDR variant (wtDDR). Overall survival was similar in the two groups (24.2 vs. 23.1 months, p = 0.63). The pDDR group had a higher median local PFS after radiotherapy (median 45 months vs. 9.9 months, respectively; p = 0.044), a higher ORR (88.9% vs. 36.2%, p = 0.04), and a longer median PFS (not reached vs. 6.0 months, p = 0.01) in patients treated with immune checkpoint blockade. There was no difference in ORR, median PFS, and median OS in patients treated with platinum-based chemotherapy. Our retrospective data suggest that in patients with stage 4 NSCLC, pathogenic variants in DDR pathway genes may be associated with higher efficacy of radiotherapy and immune checkpoint inhibitors (ICIs). This should be further explored prospectively.

Magnetic resonance-guided stereotactic body radiation therapy (MRgSBRT) for oligometastatic patients: a single-center experience.

Stereotactic body radiotherapy is increasingly used for the treatment of oligometastatic disease. Magnetic resonance-guided stereotactic radiotherapy (MRgSBRT) offers the opportunity to perform dose escalation protocols while reducing the unnecessary irradiation of the surrounding organs at risk. The aim of this retrospective, monoinstitutional study is to evaluate the feasibility and clinical benefit (CB) of MRgSBRT in the setting of oligometastatic patients. Data from oligometastatic patients treated with MRgSBRT were collected. The primary objectives were to define the 12-month progression-free survival (PFS) and local progression-free survival (LPFS) and 24-month overall survival (OS) rate. The objective response rate (ORR) included complete response (CR) and partial response (PR). CB was defined as the achievement of ORR and stable disease (SD). Toxicities were also assessed according to the CTCAE version 5.0 scale. From February 2017 to March 2021, 59 consecutive patients with a total of 80 lesions were treated by MRgSBRT on a 0.35T hybrid unit. CR and PR as well as SD were observed in 30 (37.5%), 7 (8.75%), and 17 (21.25%) lesions, respectively. Furthermore, CB was evaluated at a rate of 67.5% with an ORR of 46.25%. Median follow-up time was 14months (range: 3-46months). The 12-month LPFS and PFS rates were 70% and 23%, while 24-month OS rate was 93%. No acute toxicity was reported, whereas late pulmonary fibrosis G1 was observed in 9 patients (15.25%). MRgSBRT was well tolerated by patients with reported low toxicity levels and a satisfying CB.

Stereotactic body radiotherapy for mediastinal lymph node with CyberKnife®: Efficacy and toxicity

PuprposeStereotactic body radiotherapy is more and more used for treatment of oligometastatic mediastinal lymph nodes. The objective of this single-centre study was to evaluate its efficacy in patients with either a locoregional recurrence of a pulmonary or oesophageal cancer or with distant metastases of extrathoracic tumours. Patients and methodsPatients with oligometastatic mediastinal lymph nodes treated with CyberKnife from June 2010 to September 2020 were screened. The primary endpoint was to assess local progression free survival and induced toxicity. Secondary endpoints were overall survival and progression free survival. The delay before introduction of systemic treatment in the subgroup of patients who did not receive systemic therapy for previous progression was also evaluated. ResultsFifty patients were included: 15 with a locoregional progression of a thoracic primary tumour (87% pulmonary) and 35 with mediastinal metastasis of especially renal tumour (29%). Median follow-up was 27 months (6–110 months). Local progression free survival at 6, 12 and 18 months was respectively 94, 88 and 72%. The rate of local progression was significantly lower in patients who received 36Gy in six fractions (66% of the cohort) versus other treatment schemes. Two grade 1 acute oesophagitis and one late grade 2 pulmonary fibrosis were described. Overall survival at 12, 18 and 24 months was respectively 94, 85 and 82%. Median progression free survival was 13 months. Twenty-one patients were treated by stereotactic body irradiation alone without previous history of systemic treatment. Among this subgroup, 11 patients (52%) received a systemic treatment following stereotactic body radiotherapy with a median introduction time of 17 months (5–52 months) and 24% did not progress. ConclusionStereotactic body irradiation as treatment of oligometastatic mediastinal lymph nodes is a well-tolerated targeted irradiation that leads to a high control rate and delay the introduction of systemic therapy in selected patients.

Stereotactic body radiation therapy (SBRT) for spinal metastases: 12years of a single center experience.

To assess the clinical outcomes of patients with spine metastases treated with SBRT at our institution. Patients with spine metastases treated with SBRT (1 fraction/18Gy or 5 fractions/7Gy) during the last 12years have been analyzed. All patients were simulated supine in a vacuum cushion or with a shoulder mask. CT scans and MRI image registration were performed. Contouring was based on International Spine-Radiosurgery-Consortium-Consensus-Guidelines. Highly conformal-techniques (IMRT/VMAT) were used for treatment planning. Intra and interfraction (CBCT or X-Ray-ExacTrac) verification were mandatory. From February 2010 to January 2022, 129 patients with spinal metastases were treated with SBRT [1 fraction/18Gy (75%) or 5 fractions/7Gy] (25%). For patients with painful metastases (74/129:57%), 100% experienced an improvement in pain after SBRT. With a median follow-up of 14.2months (average 22.9; range 0.5-140) 6 patients (4.6%) experienced local relapse. Local progression-free survival was different, considering metastases's location (p < 0.04). The 1, 2 and 3years overall survival (OS) were 91.2%, 85.1% and 83.2%, respectively. Overall survival was significantly better for patients with spine metastases of breast and prostate cancers compared to other tumors (p < 0.05) and significantly worse when visceral metastases were present (p < 0.05), when patients were metastatic de novo (p < 0.05), and in those patients receiving single fraction SBRT (p: 0.01). According to our experience, SBRT for patients with spinal metastases was effective in terms of local control and useful to reach pain relief. Regarding the intent of the treatment, an adequate selection of patients is essential to propose this ablative approach.

Safety and Efficacy Results From iSABR, a Phase 1 Study of Stereotactic ABlative Radiotherapy in Combination With Durvalumab for Early-Stage Medically Inoperable Non-Small Cell Lung Cancer

To determine the safety and tolerability of combining stereotactic ablative radiotherapy (SABR) and durvalumab with respect to rates of Grade ≥3 non-hematological toxicity in medically inoperable patients with early-stage non-small cell lung cancer (NSCLC). This was a prospective multicenter trial designed as a phase II study with phase I safety lead-in enrolling from 2017- 2020. Patients with biopsy-proven clinical stage I or IIA NSCLC (per AJCC 7th edition) and were medically inoperable or refused surgery, received 1 cycle of durvalumab followed by SABR or hypofractionated radiation (54 Gy in 3 fractions [fx], 50 Gy in 4 fx, or 65 Gy in 10 fx), then up to 4 additional cycles of durvalumab (1500 mg q4 weeks). Incidence of treatment-related Grade ≥3 toxicities were tabulated. Local control (LC), progression-free survival (PFS), overall survival (OS), and lung cancer specific mortality (LCSM) were assessed using the Kaplan-Meier method. 18 patients received combination SABR and durvalumab. With a median age of 79 years, 61.1% were male, 72.2% cT1, and 27.8% cT2. 88.9% of patients were treated to 54 Gy in 3 fx and 77.8% received all 5 cycles of durvalumab. The 1- and 2-year LC rates were 100% and 93.8%, 1- and 2-year PFS rates 94.4% and 83.3%, and 1- and 2-year OS rates 94.4% and 88.9%, respectively. The 2-year cumulative incidence for LCSM was 5.6%. Patients with acute and late Grade ≥3 treatment-related toxicities included pulmonary (27.8%, 5/18), cardiac (5.6%, 1/18), and GI (0%). One Grade 5 event in the setting of previously undiagnosed interstitial lung disease (ILD) was observed. For early-stage NSCLC, combination SABR and durvalumab resulted in excellent disease specific outcomes. Safety appeared acceptable per protocol, but 5/18 patients experienced Grade ≥3 pulmonary toxicity including one Grade 5 event in a patient with ILD. Results support ongoing phase III trials determining the benefit of SABR and immune check point inhibitors in this population.

Predictive power of deep-learning segmentation based prognostication model in non-small cell lung cancer.

The study aims to create a model to predict survival outcomes for non-small cell lung cancer (NSCLC) after treatment with stereotactic body radiotherapy (SBRT) using deep-learning segmentation based prognostication (DESEP). The DESEP model was trained using imaging from 108 patients with NSCLC with various clinical stages and treatment histories. The model generated predictions based on unsupervised features learned by a deep-segmentation network from computed tomography imaging to categorize patients into high and low risk groups for overall survival (DESEP-predicted-OS), disease specific survival (DESEP-predicted-DSS), and local progression free survival (DESEP-predicted-LPFS). Serial assessments were also performed using auto-segmentation based volumetric RECISTv1.1 and computer-based unidimensional RECISTv1.1 patients was performed. There was a concordance between the DESEP-predicted-LPFS risk category and manually calculated RECISTv1.1 (φ=0.544, p=0.001). Neither the auto-segmentation based volumetric RECISTv1.1 nor the computer-based unidimensional RECISTv1.1 correlated with manual RECISTv1.1 (p=0.081 and p=0.144, respectively). While manual RECISTv1.1 correlated with LPFS (HR=6.97,3.51-13.85, c=0.70, p<0.001), it could not provide insight regarding DSS (p=0.942) or OS (p=0.662). In contrast, the DESEP-predicted methods were predictive of LPFS (HR=3.58, 1.66-7.18, c=0.60, p<0.001), OS (HR=6.31, 3.65-10.93, c=0.71, p<0.001) and DSS (HR=9.25, 4.50-19.02, c=0.69, p<0.001). The promising results of the DESEP model were reproduced for the independent, external datasets of Stanford University, classifying survival and 'dead' group in their Kaplan-Meyer curves (p = 0.019). Deep-learning segmentation based prognostication can predict LPFS as well as OS, and DSS after SBRT for NSCLC. It can be used in conjunction with current standard of care, manual RECISTv1.1 to provide additional insights regarding DSS and OS in NSCLC patients receiving SBRT. While current standard of care, manual RECISTv1.1 correlated with local progression free survival (LPFS) (HR=6.97,3.51-13.85, c=0.70, p<0.001), it could not provide insight regarding disease specific survival (DSS) (p=0.942) or overall survival (OS) (p=0.662). In contrast, the deep-learning segmentation based prognostication (DESEP)-predicted methods were predictive of LPFS (HR=3.58, 1.66-7.18, c=0.60, p<0.001), OS (HR=6.31, 3.65-10.93, c=0.71, p<0.001) and DSS (HR=9.25, 4.50-19.02, c=0.69, p<0.001). DESEP can be used in conjunction with current standard of care, manual RECISTv1.1 to provide additional insights regarding DSS and OS in NSCLC patients.

Abstract 5122: Electrochemotherapy and IL-12 gene electrotransfer in treatment of mast cell tumors in companion dogs

Abstract When cells or tissues are exposed to an electric field, structural changes can be induced in the cell membrane, allowing molecules to flow into the cells. This condition is useful for delivering cytotoxic drugs whose transport into cells is impeded, such as bleomycin and cisplatin. This is referred to as electrochemotherapy (ECT). When DNA or RNA molecules are transported into cells, the approach is called gene electrotransfer (GET). ECT is an effective local treatment for tumors, but it lacks the systemic component of treatment that is essential for fighting metastatic disease. Cancer progression and metastasis are closely related to an inadequate antitumor immune response. Therefore, the antitumor efficacy of interleukin 12 (IL -12), a cytokine that stimulates the innate and adaptive immune response, has been tested in preclinical studies using plasmid DNA encoding IL -12 delivered into the tumor by gene electrotransfer (IL -12 GET). In addition, the combined treatment of ECT and IL -12 GET has already been shown to be effective in the treatment of mouse tumors and has been used in clinical trials in companion dogs to treat various histological types of spontaneous tumors. The results of these studies showed that the treatment is safe and effective. However, in these clinical trials, IL -12 GET was administered by different routes, either intratumorally (i.t.) or peritumorally (peri.t.). Therefore, the aim of this study was to compare the two IL -12 GET routes of administration in combination with ECT and to determine their contribution to the enhanced response to ECT. In the clinical trial, 59 dogs with spontaneous mast cell tumors (MCT) were divided into two groups: one group was treated with the combination of ECT and GET peri.t. (29 dogs) and the other with the combination of ECT + GET i.t. (30 dogs). The efficacy of the treatment was compared with the group of 18 dogs treated with ECT alone. In addition, immunohistochemical studies of tumor samples before treatment and flow cytometric studies of PMBC before and after treatment were performed to determine immunological aspects of the treatment. The results of this study showed that local tumor control was significantly better in the ECT + GET i.t. group (p &amp;lt; 0.05) than in the ECT + GET peri.t. and ECT groups. In addition, the disease-free interval (DFI) and progression-free survival (PFS) were significantly longer in the ECT + GET i.t. group than in the other two groups (p &amp;lt; 0.05). The data on local tumor response, DFI and PFS were consistent with immunological studies, as we detected increased infiltration of antitumor immune cells after treatment in the ECT + GET i.t. group, also suggesting a systemic effect. Citation Format: Maja Cemazar, Ursa Lampreht Tratar, Nina Milevoj, Katarina Znidar, Katja Ursic Valentinuzzi, Andreja Brozic, Gregor Sersa, Natasa Tozon. Electrochemotherapy and IL-12 gene electrotransfer in treatment of mast cell tumors in companion dogs. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5122.

Synchronous computed tomography-guided percutaneous biopsy and microwave ablation for highly suspicious malignant lung ground-glass opacities adjacent to mediastinum

Background This retrospective study aimed to assess the safety and efficacy of synchronous biopsy and microwave ablation (MWA) for highly suspected malignant lung ground-glass opacities (GGOs) adjacent to the mediastinum (distance ≤10 mm). Materials and methods Ninety patients with 98 GGOs (diameter range, 6–30 mm), located within 10 mm of the mediastinum, underwent synchronous biopsy and MWA at a single institution from 1 May 2020, to 31 October 2021 and were enrolled in this study. Synchronous biopsy and MWA involving the completion of the biopsy and MWA in a single procedure was performed. Safety, technical success rate, and local progression-free survival (LPFS) were evaluated. The risk factors for local progression were calculated using the Mann–Whitney U test. Results The technical success rate was 97.96% (96/98 patients). The LPFS rates at 3, 6, and 12 months were 95.0%, 90.0%, and 82.0%, respectively. The diagnostic rate of biopsy-proven malignancy was 72.45% (n = 71/98). Invasion of lesions into the mediastinum was a risk factor for local progression (p = 0.0077). The 30-day mortality rate was 0. The major complications were pneumothorax (13.27%), ventricular arrhythmias (3.06%), pleural effusion (1.02%), hemoptysis (1.02%), and infection (1.02%). Minor complications included pneumothorax (30.61%), pleural effusion (24.49%), hemoptysis (18.37%), ventricular arrhythmias (11.22%), structural changes in adjacent organs (3.06%), and infection (3.06%). Conclusions Synchronous biopsy and MWA was effective for treating GGOs adjacent to the mediastinum without severe complications (Society of Interventional Radiology classification E or F). Invasion of lesions into the mediastinum was identified as a risk factor for local progression.

Long-term follow-up results of spine tumor treatment using high-dose radiotherapy after 3-dimensional-printed vertebral bodies implantation.

To investigate the long-term safety and efficacy of high-dose radiotherapy after 3D-printed vertebral body implantation in the treatment of spinal tumors. Thirty-three participants were recruited between July 2017 and August 2019. 3D-printed vertebral bodies were implanted in each participant, followed by postoperative robotic stereotactic radiosurgery at a dose of 35-40 Gy/5f. The tolerance of the 3D-printed vertebral body and the participant to the high-dose radiotherapy were evaluated. In addition, the local control of tumor and the local progression-free survival of the study participants following 3D-printed vertebral body implantation and high-dose radiotherapy were measured as indexes of effectiveness. Of the 33 participants included in the study, 30, including three participants (10%) with esophagitis of grade 3 or above and two participants (6.7%) with advanced radiation nerve injury, successfully underwent postoperative high-dose radiotherapy. The median follow-up was 26.7 months, and IQR was 15.9 months. Most participants had primary bone tumors with 27 cases (81.8%), and the rest had bone metastases in six cases (18.2%). After high-dose radiotherapy, the 3D-printed vertebrae maintained good vertebral stability and exhibited histocompatibility, without implant fractures. The local control rates were 100%, 88%, and 85% 6 months, 1 year, and 2 years after high-dose radiotherapy, respectively. Tumors recurred in four participants (12.1%) during the follow-up period. The median local progression-free survival after treatment was 25.7 months, with a range of 9.6-33.0 months. High-dose radiotherapy for spinal tumors after 3D-printed vertebral body implantation is feasible, elicits low toxicity, and yields satisfactory tumor control.

Longer Survival and Preserved Liver Function after Proton Beam Therapy for Patients with Unresectable Hepatocellular Carcinoma

Proton beam therapy (PBT) has been recently reported to achieve excellent tumor control with minimal toxicity in patients with unresectable hepatocellular carcinoma (HCC). Radiofrequency ablation (RFA) combined with transcatheter arterial chemoembolization (TACE) was investigated for larger HCC. This study was designed to evaluate the therapeutic effect of PBT on unresectable HCC in comparison with TACE combined with RFA. We retrospectively analyzed 70 patients with HCC which was difficult to control by surgical resection or RFA monotherapy, 24 patients treated with PBT and 46 patients with TACE plus RFA. The therapeutic effects were assessed as local progression-free survival (PFS) and overall survival (OS). The local PFS was more than 65% in 60 months for PBT and TACE plus RFA. The patients treated with PBT showed 82% OS at 60 months post-treatment. In contrast, those treated with TACE plus RFA showed 28% OS. When comparing the changes of ALBI scores in patients with different severities of chronic liver disease, the scores of PBT-treated patients were maintained at the baseline; however, those of TACE plus RFA-treated patients worsened after the treatments. The results indicated that PBT may show better benefits than TACE plus RFA therapy in terms of OS in patients with unresectable HCC by sparing the non-tumor liver tissues.

Efficacy of concurrent radiotherapy in patients with locally advanced rectal cancer and synchronous metastasis receiving systemic therapy.

Neoadjuvant chemoradiotherapy followed by total mesorectal excision is the standard treatment for patients with nonmetastatic locally advanced rectal cancer (LARC). However, for patients with LARC and synchronous metastasis, the optimal treatment strategy and sequence remain inconclusive. In the present study, we evaluated the efficacy and safety of concurrent radiotherapy in patients with de novo metastatic rectal cancer who received chemotherapy and targeted therapy. We retrospectively reviewed the data of 63 patients with LARC and synchronous metastasis who received intensive therapy at the study hospital between April 2015 and November 2018. The included patients were divided into two groups: RT-CT, those who received systemic chemotherapy with targeted therapy and concurrent radiotherapy (for primary rectal cancer), and CT, those who received only systemic chemotherapy with targeted therapy. Treatment response was better in the RT-CT group than in the CT group. The rate of primary tumor resection (PTR) was higher in the RT-CT group than in the CT group (71.4% and 42.9%, respectively; P = .0286). The RT-CT group exhibited considerably longer local recurrence-free survival (P = .0453) and progression-free survival (PFS; from 13.3 to 22.5 months) than did the CT group (P = .0091); however, the groups did not differ in terms of overall survival (OS; P = .49). Adverse events were almost similar between the groups, except frequent diarrhea, the prevalence of which was higher in the RT-CT group than in the CT group (59.5% and 23.8%, respectively; P = .0075). In the era of biologics, radiotherapy may increase the resectability of primary rectal tumors, reducing the risk of locoregional failure and prolonging PFS. Concurrent pelvic radiotherapy may not substantially improve OS, which is indicated by metastasis. Hence, the resection of the distant metastases may be essential for improving long-term OS. To further determine the efficacy of concurrent radiotherapy, additional prospective, randomized studies must combine preoperative pelvic radiotherapy with PTR and metastectomy to treat patients with stage IV LARC.