Local Relapse Research Articles

Case Report: Remarkable breakthrough: successful treatment of a rare intracranial mesenchymal, FET::CREB fusion-positive tumor treated with patient-tailored multimodal therapy

BackgroundIntracranial mesenchymal tumors are a rare type of neoplasm (0.3% of all soft tissue tumors) characterized by a fusion of a FET family gene (usually EWSR1, rarely FUS) to CREB family genes (CREB1, ATF1, and CREM) with a slow-growing and favorable prognosis. Mesenchymal tumors are most frequently localized in the subcutaneous tissue (typically in the limbs and hands) of young adults and have rarely been diagnosed in the central nervous system. Surgery is the gold standard treatment; adjuvant radiation therapy and chemotherapy with sarcoma-based regimens have been used in rare cases when complete surgical excision was not recommended. In terms of prognosis, these tumors show a tendency for local relapse. The longest patient outcomes reported in the literature are five years.Case descriptionThis case describes a 27-year-old woman with unconventional extracranial metastatic sites of myxoid intracranial mesenchymal tumor FET::CREB fusion-positive and high expression of PD-1 (40%) and PD-L1 (30%). Based on clinical, molecular, and histological characteristics, she underwent various local and systemic therapies, including surgery, proton beam therapy, the use of immune checkpoint inhibitors, and chemotherapy. These treatments led to a complete remission of the disease after eight years from tumor diagnosis.ConclusionsOur case sheds light on the importance of precision medicine and tailored therapy to explore new treatment opportunities for rare or unknown tumor entities.

Surgical Strategy for Recurrent Giant Cell Tumor in the Thoracolumbar Spine.

Recurrent giant cell tumor (RGCT) of the spine represents a clinical challenge for surgeons, and the treatment strategy remains controversial. This study aims to describe the long-term follow-up outcomes and compare the efficacy of en bloc spondylectomy versus piecemeal spondylectomy in treating RGCT of the thoracolumbar spine. A total of 32 patients with RGCT of the thoracolumbar spine treated from June 2012 to June 2019 were retrospectively reviewed. A total of 15 patients received total en bloc spondylectomy (TES) with wide or marginal margin while 17 patients received total piecemeal spondylectomy (TPS) with intralesional margin. Postoperative Eastern Cooperative Oncology Group Performance Score (ECOG-PS), Frankel classification and recurrence-free survival (RFS) were evaluated after surgery. Survival curves were estimated by the Kaplan-Meier method and differences were analyzed with the log-rank test. Multivariate analysis was performed with Cox regression to identify the independent prognostic factors affecting RFS. During a median follow-up of 41.9 ± 17.5 months, all patients with compromised neurologic functions exhibit significant improvement, with the mean ECOG-PS decreasing from 1.5 ± 1.3 to 0.13 ± 0.3 (p < 0.05). Among the 17 patients treated with TPS, eight patients developed local recurrence after a median time of 15.9 ± 6.4 months and four patients died from progressive disease. On the other hand, local recurrence were well managed with TES, since only one out of 15 patients experienced local relapse and all patients are alive with satisfied function at the latest follow-up. The median RFS for patients receiving TES and TPS are 75.0 months (95% CI: 67.5-82.5 m) and 38.3 months (95% CI: 27.3-49.3 m) respectively (p = 0.008). Multivariate analysis shows that the Ki67 index (p = 0.016), resection mode (p = 0.022), and denosumab (p = 0.039) are independent risk factors affecting RFS. TES with wide/marginal margin should be offered to patients with RGCT whenever feasible, given its long-term benefits in local control and symptom alleviation. Additionally, patients with lower Ki67 index and application of denosumab tend to have a better prognosis.

Ultra Low Dose 4 Gy Radiation for Definitive Therapy of Gastric MALT Lymphoma

Introduction Definitive treatment for early-stage gastric MALT (mucosa-associated lymphoid tissue) lymphoma typically includes radiation therapy (RT) to doses of 24-30 Gy. Given the favorable prognosis of this disease, there is considerable interest in decreasing the toxicity profile of treatment. We prospectively investigated outcomes using a response-adapted (RA) approach giving an initial 4 Gy (ultra-low dose (ULD)) RT with an additional 20 Gy only for incomplete response (Figure 1). We hypothesized that this RA-approach would maintain excellent outcomes with limited toxicity. Methods We performed a single-arm prospective trial of ULD RT in 24 patients (age ≥18 years) with newly diagnosed or relapsed stage I-IV H. pylori (HP) negative gastric MALT lymphoma (NCT03680586). Patients with residual lymphoma after HP eradication were eligible. Patients with bulky disease (&amp;gt;10 cm) were excluded. Patients were treated with 4 Gy in 2 fractions and assessed with endoscopy and imaging at 3-4 months post-RT. Patients with a complete response (CR) assessed by endoscopy with biopsies and imaging were observed. Patients with a partial response (PR) by endoscopic, pathologic or radiographic evaluations were re-evaluated in 6-9 months. Biopsy-confirmed residual disease at the second timepoint (9-13 months) or stable disease (SD)/progressive disease (PD) at any time point prompted treatment with an additional 20 Gy in 10 fractions. Systemic therapy was permitted if clinically indicated. Results We enrolled 24 patients from 2019-2021. Median age was 67 (range 40-85) with 15 female patients (63%). Patients had stage I (n=20, 83%), II (n=1, 4%), and IV (n=3, 13%) disease. Of 15 tested patients, 4 were positive for t(11;18). Patients had pre-treatment imaging with fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) (n=21), contrasted CT (n=2), and contrasted magnetic resonance imaging (MRI) (n=1). Eight patients had prior treatment including systemic therapy (n=2, 8%) or antibiotics for HP positive (n=3, 13%) or HP negative (n=3, 13%) disease. Of 3 patients with prior HP positive disease, residual lymphoma was documented after eradication at 18 months (PR), 11 months (SD), and 8 months (disease relapse after CR) post-diagnosis. Median follow-up for the entire cohort was 34 months (95% CI 22-40) based on the reverse Kaplan-Meier estimator. Sixteen patients had a CR at first evaluation (3-4 months) after 4 Gy, and an additional 4 patients had disease conversion to CR at second evaluation (9-13 months), for a total of 20 patients (83%) who had a CR to 4 Gy at a median time of 4 months (range 3-12). No patients had positive imaging findings with a pathologic CR. One local relapse occurred 14 months post-treatment after a CR to 4 Gy. This patient received 20 Gy and again experienced a CR. Four patients received an additional 20 Gy for SD/PD or residual disease after 4 Gy. Two patients received 20 Gy for symptomatic SD at 3-4 months, both with a CR following RA therapy. Two patients received 20 Gy for residual disease at 10 and 13 months. One patient had a CR and one is pending last follow-up. Two of the 4 patients (50%) with a positive t(11;18) required an additional 20 Gy RT compared with 3 of 11 (27%) patients without the translocation (p=0.56) The rate of 3-year LC for 23 patients who had complete follow-up was 100%, with 19 of 24 patients (79%) with a CR at last follow-up after only the initial 4 Gy. One patient with stage IV disease experienced distant relapse with diffuse large B cell lymphoma and is in CR after systemic therapy. No additional patients received systemic therapy after RT. RT was well tolerated with no grade 3 or higher acute or late toxicities. Conclusions Most patients with gastric MALT lymphoma experienced a CR after only 4 Gy RT; for those requiring an additional 20 Gy with completed follow-up, all experienced a CR. This strategy could be considered to select only those patients who benefit from longer RT courses and spare most patients from unnecessary treatment toxicity. It is important to allow adequate time for response with this indolent disease. Additional follow-up is required to confirm long-term excellent outcomes with RA ULD treatment.

Upfront Radiation Therapy (RT) for Post-Stem Cell Transplant Multiple Myeloma (MM) Patients with Oligo-Relapse/Progressive Disease: Factors Associated with Favorable Outcomes

Introduction: Relapsed or refractory disease post-stem cell transplant (SCT) for Multiple Myeloma (MM) can be clinically challenging. For localized relapses, radiation therapy (RT) can represent an attractive treatment modality. However, data on outcomes with RT remains scarce. We investigated the impact of RT as a treatment modality in the setting of oligo-relapse and oligo-progressive plasmacytomas after SCT and explored prognostic factors associated with favorable long-term outcome Methods: In this single-institution retrospective analysis, we identified 31 MM patients who underwent upfront RT for oligo-relapse or oligo-progressive MM after SCT between 2000 and 2021. Patients were excluded if they had received systemic therapy for evidence of concurrent biochemical relapse prior to RT start. The treatment responses to stem cell transplantation (SCT) and RT were assessed following the response criteria established by the International Myeloma Working Group (IMWG), which includes the categories: complete response (CR), very good partial response (VGPR), partial response (PR), minimal response (MR), stable disease (SD) and progressive disease (PD). Additionally, we utilized the R-ISS staging system to classify patients into Standard-Risk (R-ISS I), Intermediate-Risk (R-ISS II), and High-Risk (R-ISS III) groups, to allow for a comprehensive evaluation of treatment efficacy and outcomes. Results: Disease and treatment characteristics for the cohort are summarized inFigure 1. Of the 27 patients with imaging available prior to SCT, 67% (18) were assessed with PET, 22% (6) with skeletal survey, 3.7% (1) with MRI/CT, 3.7% with CT, and 3.7% (1) with x-ray. Following SCT, 48% (13) of patients were noted to have radiographic progression, 23% (7) had sCR, 23% (7) had a CR, 10% had a serologic CR, and 45% (14) had a VGPR. Among the 18 patients with radiographic evaluation (in addition to bone marrow biopsy and/or labs) post-SCT, 67% (12) were in radiographic CR at time of re-staging. Median times from SCT to new site of oligo-relapsed disease (20, 64.5%) and pre-existing but inactive sites of oligo-relapsed MM (4, 12.9%) were 31 months (3.2-117.5) and 9 months (3.4-15.9), respectively. Oligo-progressive MM, defined as active sites of disease both pre- and post-SCT were present in 22.6% (7) of patients. Prior to RT, 94% (29) had PET/CT imaging, with a median SUV of 4.4 (2.6-7.2) for target lesions. Solitary bone (77%) and extramedullary (23%) disease were treated to median dose of 30 Gy (8-49 Gy). At first disease response assessment post-RT, 77% (24) of which was done with PET/CT imaging , 42% (13) achieved CR. Among the 18 patients that did not achieve CR, 15 subsequently achieved CR at a median time of 7 months (1.7-44.5). A majority of patients (87%) received systemic therapy post-RT, with a median number of lines of therapy post-RT of 3 (1-17). The remaining 13% (4) of patients did not receive additional systemic therapy post-RT and did not experience progression. Median overall survival for the full cohort was 38 months (3.5-37.9). Conclusions: Utilizing modern systemic therapies in combination with post-transplant RT for patients with limited refractory or relapsed MM is a promising therapeutic approach. For those that remain refractory or relapse in a single site RT local control merits consideration supported by our report. Further investigation to identify patients at highest risk of progression and who may therefore benefit most from RT would be valuable. We plan to conduct additional analyses on the radiographic characteristics that may portend high risk disease, with the ultimate goal of developing well-defined criteria for giving RT earlier.

Salvage pleurectomy/decortication following immunotherapy for malignant pleural mesothelioma.

Salvage surgery following immunotherapy is a promising treatment option for advanced malignant tumour. However, only a few cases of salvage surgery for malignant pleural mesothelioma (MPM) have been reported. This retrospective study was conducted to assess the feasibility of salvage surgery following immunotherapy for initially unresectabele MPM. Among 61 patients who received pleurectomy/decortication (P/D) for MPM, 7 patients received salvage P/D after immunotherapy. Surgical indication of salvage P/D was conversion to resectability in 5 patients and local relapse in 2 patients, and macroscopic complete resection was achieved in all patients. Although salvage P/D was associated with longer operation time (median, 507 min), higher intraoperative blood loss (median, 2573 mL) and higher morbidity (≥ grade 3, 29%), no patient died after surgery. Radiographic response to immunotherapy was well correlated with pathologic response, as all 4 patients with partial response showed significant pathologic response (viable cells, ≤50%). With the median postoperative follow-up duration of 9.0 months, all patients were alive mostly without tumour recurrence as local recurrence developed in 1 patient. To conclude, salvage P/D after immunotherapy may be a feasible treatment option for selected patients with advanced MPM, which should be validated in future multi-institutional studies. In addition, a long-term follow-up is essential to reveal the clinical benefit achieved with salvage P/D following immunotherapy.

Curative carbon ion radiotherapy in a head and neck mucosal melanoma series: Facing the future within multidisciplinarity

PurposeTo evaluate efficacy and toxicity of carbon ion radiotherapy (CIRT) in locally advanced head and neck mucosal melanoma (HNMM) patients treated at our Institute. Materials and MethodsBetween June 2013 and June 2020, 40 HNMM patients were treated with CIRT. Prescription dose was 65.6-68.8 Gy relative biological effectiveness [RBE] in 16 fractions. Twelve (30%) patients received only biopsy, 28 (70%) surgical resection before CIRT. Immunotherapy was administered before and/or after CIRT in 45% of patients, mainly for distant progression (89%). ResultsMedian follow-up was 18 months. 2-year Local Relapse Free Survival (LRFS), Overall Survival (OS), Progression Free Survival (PFS) and Distant Metastasis Free Survival (DMFS) were 84.5%, 58.6%, 33.2% and 37.3%, respectively. At univariate analysis, LRFS was significantly better for non-recurrent status, < 2 surgeries before CIRT and treatment started < 9 months from the initial diagnosis, with no significant differences for operated versus unresected patients. After relapse, immunotherapy provided longer median OS (17 months vs 3.6, p-value<0.001). Late toxicity ≥ G3 (graded with CTCAE 5.0 scale) was reported in 10% of patients. ConclusionCIRT in advanced HNMM patients is safe and locally effective. Prospective trials are warranted to assess the role of targeted/immune- systemic therapy to improve OS.

NIMG-05. CHARACTERIZATION OF LONG-TERM METABOLIC CHANGES OF BRAIN METASTASES AFTER TREATMENT WITH STEREOTACTIC RADIOSURGERY USING SERIAL FET PET IMAGING

Abstract BACKGROUND In the present study, we characterized the long-term metabolic changes of brain metastases after treatment with stereotactic radiosurgery (SRS) by serial PET imaging using the radiolabeled amino acid O-(2-[18F]-fluoroethyl)-L-tyrosine (FET). We hypothesized that this approach is of considerable clinical value in differentiating between radiation-induced changes and local brain metastasis relapse. Patients and METHODS From 2010-2020, we retrospectively identified patients with brain metastases from solid extracranial primary tumors who (i) were treated with SRS with or without concurrent immunotherapy using checkpoint inhibitors, (ii) had equivocal MRI findings after SRS, and (iii) subsequently underwent two or more additional FET PET scans during follow-up for long-term evaluation. Mean tumor-to-brain ratios (TBR) were obtained. Diagnostic performances were calculated using receiver operating characteristic curve analyses. Diagnoses were confirmed by neuropathological evaluation (29%) or clinicoradiologically (71%). RESULTS We identified 14 patients with 42 FET PET scans (median number, 3; range, 2-4). Concurrent to SRS, 4 patients (29%) were treated with checkpoint inhibitors. Following SRS, equivocal MRI findings occurred after a median time of 7 months (range, 2-62 months). Subsequently, FET PET scans were acquired over a median 16 months (range, 7-99 months). Nine patients (64%) had radiation-induced changes, and five had local brain metastases relapse. TBRs calculated from the last available FET PET scan showed the highest accuracy (93%) in identifying radiation-induced changes (threshold, 1.95; P=0.011). In lesions consistent with local brain metastases relapse, TBR increased considerably over time (median increase, 17%; range, 11% - 32%). In contrast, in lesions considered as radiation-induced changes, TBR remained stable or even decreased (median change, -4%; range, -44% - 11%). The TBR evolution over time significantly differed between the two groups (P=0.011). CONCLUSIONS Serial FET PET imaging has a high diagnostic accuracy for characterizing long-term changes of brain metastases after treatment with stereotactic radiosurgery.

EXTH-66. SINGLE-CELL SPATIOTEMPORAL GENOMICS REVEALS CLONAL EVOLUTION AND THERAPEUTIC TARGET IN RECURRENT DISSEMINATED MEDULLOBLASTOMA

Abstract Despite the cellular heterogeneity observed in single-cell studies of medulloblastoma, limited knowledge exists regarding the genetic features and spatiotemporal states of specific cell populations following tumor relapse and dissemination, leading to a lack of effective treatment strategies. In this study, we conducted single-cell transcriptomic, chromatin accessibility, and spatial transcriptomic analyses on 15 primary and recurrent Group 3 medulloblastomas, along with two PDX models (including a lung metastasis model). Subsequently, we deconvoluted our findings with our RNA-seq cohort to further validate cell cluster-specific gene expression associated with relapse and its prognostic significance. We analyzed malignant cells, including cancer stem cells (MB-CSCs), proliferating cells, and differentiated cell populations, and examined gene expression features closely associated with clinical prognosis. To elucidate the origin and maturation process of these malignant cells accurately, we compared tumor cell profiles with early human cerebellar cell-types. Furthermore, we described the spatiotemporal transitions from MB-CSCs to terminal states, with a particular emphasis on the extensive spatial heterogeneity within the tumor during the processes of primary, local relapse, and dissemination. Through computational non-negative matrix factorization (cNMF) analysis, we identified a group of tumor cells in recurrent Group 3 medulloblastoma with high cellular plasticity (HCP), demonstrating strong stemness and proliferative capabilities, as well as the ability to differentiate into multiple functional tumor cell subgroups. This cell population exhibited elevated expression of PTPRZ1, which phosphorylates downstream molecules to promote tumor progression. Through single-cell transcriptomic and chromatin accessibility analyses, we validated the expression of PTPRZ1 in human samples, PDX samples, and transgenic mouse samples. In vitro and in vivo inhibition of PTPRZ1 function using small molecule inhibitors effectively suppressed tumor proliferation and metastatic activity. By employing single-cell spatiotemporal genomics, we elucidated the evolutionary states and subclonal events of primary and recurrent medulloblastoma, and identified PTPRZ1 as a target for effectively inhibiting tumor progression.

RADT-34. CLINICAL OUTCOMES OF LOCALISED AND METASTATIC CENTRAL NERVOUS SYSTEM HAEMANGIOPERICYTOMAS/SOLITARY FIBROUS TUMOURS – A SINGLE INSTITUTION EXPERIENCE

Abstract BACKGROUND/OBJECTIVE Central nervous system (CNS) haemangiopericytomas (HPC) or solitary fibrous tumours (SFT) are rare aggressive tumours. Surgery is the primary modality of treatment, however, often followed by postoperative radiotherapy due to high tendency for local recurrence. Although rare, extracranial metastases to several sites have been described. We aim to report our institutional experience in managing these rare tumours. METHODS Patients with central nervous system HPC/SFT who underwent surgical resection from 2012 to 2022 were included in the study. Data collected included patient demographics, tumour characteristics, treatment details (including primary surgery, radiotherapy and treatment for relapse) and clinical outcomes. RESULTS Five patients were included in this study. All were women and their mean age at diagnosis was 43 years. Four patients presented with intracranial disease and one with cervico-thoracic spine disease. All patients had undergone primary surgery and gross total resection was achieved in two patients. Two patients had grade 1, one with grade 2 and two with grade 3 HPC. Four patients received radiotherapy (median dose 60Gy) and one was on imaging surveillance after surgery. Three patients had relapsed – one with locoregional relapse only, one with distant (liver and bone) relapse and other with locoregional and distant (lung and bone). Time to relapse were 192, 39 and 120 months respectively. Stereotactic radiotherapy was used to treat local relapse in posterior fossa and dura of cervical spine, and metastatic relapse in lung with a stable radiological response. One patient with a painful destructive bone metastases was treated with palliative radiotherapy with good pain control. Four patients were alive at the time of the study, and one was lost to follow up. CONCLUSION We present our institutional experience in management of localised and metastatic HPC/SFT. Stereotactic radiotherapy could be considered an effective treatment modality for small volume relapse of HPC.

Prognosis of Adrenal Oncocytic Neoplasms (AONs): Literature Review of 287 Cases and Presentation of the Oldest Patient.

The adrenocortical oncocytic neoplasms (AONs) are rare tumors of the adrenal gland, classified as oncocytoma (AO), oncocytic neoplasm of uncertain malignant potential (AONUMP) and oncocytic carcinoma (AOC). The aim of this study was to perform a review of the literature, in order to evaluate the prognosis of these rare cancers. We also reported the oldest patient with AON. A comprehensive literature review using as key words "adrenal oncocytoma", "adrenal oncocytic neoplasm", and "adrenal oncocytic carcinoma" was performed. We report the case of an 88-year-old woman receiving a left open adrenalectomy for an AON (15 × 10 × 8 cm). The considerable size and weight together with the presence of necrosis were indicative for a lesion with an uncertain potential for malignancy, according to Weiss modified criteria. After two years, the patient was free from any sign of recurrence. Only 287 AONs were detected in the scientific literature, exploring OVID, MEDLINE, PubMed and SCOPUS as dataset. These tumors are usually incidentalomas with an unpredictable malignant potential. Surgical resection remains the mainstay of treatment for AON. AO and AONUMP have an excellent prognosis and a low mortality rate, with only three cases of recurrence reported in the literature and one metastatic case four years after first adrenal surgery. In contrast, AOC carries a high risk of local relapses, distant metastasis, and a significantly higher mortality rate (30%). Surgical resection remains the primary treatment for adrenal oncocytic neoplasms.

Chimeric Antigen Receptor-T Cell Therapy Decreases Distant Metastasis and Inhibits Local Recurrence Post-surgery in Mice.

Distant metastasis and primary tumor relapse are the two main hurdles to the success of surgical treatment for cancer patients. Circulating tumor cells (CTCs) and incomplete surgical resection are the primary cause of distant metastasis and local recurrence of tumors, respectively. Chimeric antigen receptor (CAR)-modified T cells target residual carcinomas and CTCs hold the potential to inhibit primary recurrence and reduce tumor metastasis, but the experimental evidence is lacking. Here, we developed a surgery-induced tumor metastasis model in immunocompetent mice to investigate the efficacy of CAR-T cells therapy in preventing metastasis and local recurrence. We observed that subcutaneous tumor resection has induced a large number of CTCs intravasated into circulation. EpCAM-specific CAR-T was effective in clearing CTCs following surgical removal of the tumor. This resulted in less pulmonary metastasis and longer survival in mice when compared to mice treated with surgery followed by Mock-T cells infusion. In addition, the local relapse was obviously inhibited at the surgical site followed by EpCAM-CAR-T cell treatment. This study demonstrated that CAR-T cell therapy can be an adjuvant treatment following surgery to prevent tumor metastasis and inhibit primary tumor relapse for cancer patients.

P027 - Stereotactic re-irradiation for local relapse after prostate/prostate-bed radiotherapy

P027 - Stereotactic re-irradiation for local relapse after prostate/prostate-bed radiotherapy

Impact of Surveillance Imaging in Detecting Local and Metastatic Lung Recurrences Among Patients with Sarcomas of the Extremities: A Systematic Review and Meta-analysis.

The surveillance guidelines following treatment completion for patients with high-grade sarcomas of the extremities are based largely upon expert opinions and consensus. In the current meta-analysis, we aim to study the utility of surveillance imaging to diagnose local and metastatic pulmonary relapses among patients with extremity soft tissue sarcomas and primary bone sarcomas. A meta-analysis was performed to assess the sensitivity, specificity and diagnostic odds ratio (DOR) of surveillance imaging to diagnose local and metastatic pulmonary relapse among patients with sarcoma of the extremities. In addition, impact of surveillance imaging on overall survival was assessed. Heterogeneity among eligible studies was evaluated by I2 statistics. Sensitivity analysis was assessed using influence plots and Baujat plots. Ten studies including 2160 patients with sarcoma were found eligible. For diagnoses of local recurrence based on surveillance imaging (nine studies, 1917 patients), the estimated sensitivity, specificity, and DOR were 13.6%, 99.5%, and 78.15, respectively. Only 16.7% of local recurrences were diagnosed based on imaging. For diagnoses of metastatic pulmonary recurrence (eight studies; 1868 patients), estimated sensitivity, specificity, and DOR were 76.1%, 99.3%, and 1059.9, respectively. A sensitivity analysis showed significant heterogeneity among included studies. None of the included studies showed an overall-survival benefit with the use of surveillance imaging. The current meta-analysis challenges the notion of routine use of imaging to detect local relapse, while favoring chest imaging, using either chest radiography or computed tomography scan, for surveillance. Further studies are required to study the ideal surveillance strategy including timing and imaging modality.

Comparison of early and late 68Ga-FAPI-46-PET in 33 patients with possible recurrence of pancreatic ductal adenocarcinomas

Positron emission tomography with 68Gallium (68Ga) labeled inhibitors of fibroblast activation protein (68Ga-FAPI-PET) is a promising imaging technique for patients with recurrent pancreatic ductal adenocarcinomas (PDAC). To date, it is not clear if different acquisition timepoints for 68Ga-FAPI-PET may result in comparable imaging information and if repetitive 68Ga-FAPI-PET imaging may add diagnostic value to single timepoint acquisition for recurrent PDAC. Here we analyzed retrospectively early (20 min p.i.) and late (60 min p.i.) 68Ga-FAPI-PET imaging using FAPI-46 of 33 patients with possible recurrence of PDAC concerning detection rates and uptake over time of local recurrences, metastases, inflammatory lesions of the pancreas, cholestatic lesions of the liver and reactive tissue. 33 patients with histologically confirmed PDAC after complete or partial resection of the pancreas and possible recurrence were examined by 68Ga-FAPI-46-PET acquired 20- and 60-min post injection (p.i.) of the radiotracer. FAPI-positive lesions were classified as local recurrences, metastases, inflammatory lesions of the pancreas (ILP), cholestatic lesions of the liver and reactive tissue based on histology, PET- and CT-morphology and clinical information. Lesions were contoured, and standardized uptake values (SUVmax and SUVmean) and target-to-background ratios (TBR) were analyzed for both acquisition timepoints. In total, 152 FAPI-positive lesions (22 local relapses, 47 metastases, 26 inflammatory lesions of the pancreas, 28 reactive tissues, and 29 cholestatic lesions) were detected. Detection rates for the early and late acquisition of 68Ga-FAPI-46-PET were almost identical except cholestatic lesions, which showed a higher detection rate at early imaging. SUV parameters and TBRs of ILP significantly decreased over time. Cholestatic lesions showed a tendency towards decreasing uptake. All other types of lesions showed relatively stable uptake over time. Early and late acquisition of 68Ga-FAPI-PET results in comparable imaging information in patients with possible recurrence of PDAC. Two timepoint imaging offers additional diagnostic potential concerning differential diagnoses.

Self-sufficient nanoparticles with dual-enzyme activity trigger radical storms and activate cascade-amplified antitumor immunologic responses

Radiotherapy (RT) can potentially induce systemic immune responses by initiating immunogenic cell death (ICD) of tumor cells. However, RT-induced antitumor immunologic responses are sporadic and insufficient against cancer metastases. Herein, we construct multifunctional self-sufficient nanoparticles (MARS) with dual-enzyme activity (GOx and peroxidase-like) to trigger radical storms and activate the cascade-amplified systemic immune responses to suppress both local tumors and metastatic relapse. In addition to limiting the Warburg effect to actualize starvation therapy, MARS catalyzes glucose to produce hydrogen peroxide (H2O2), which is then used in the Cu+-mediated Fenton-like reaction and RT sensitization. RT and chemodynamic therapy produce reactive oxygen species in the form of radical storms, which have a robust ICD impact on mobilizing the immune system. Thus, when MARS is combined with RT, potent systemic antitumor immunity can be generated by activating antigen-presenting cells, promoting dendritic cells maturation, increasing the infiltration of cytotoxic T lymphocytes, and reprogramming the immunosuppressive tumor microenvironment. Furthermore, the synergistic therapy of RT and MARS effectively suppresses local tumor growth, increases mouse longevity, and results in a 90% reduction in lung metastasis and postoperative recurrence. Overall, we provide a viable approach to treating cancer by inducing radical storms and activating cascade-amplified systemic immunity.

Oncological Skull Base Reconstruction with Microvascular Tissue Transplantation in Advanced Relapsed Cases

Introduction: Tumors involving the skull base are real challenges to reconstructive surgeons. Many articles have been published about these reconstructions, especially in primary cases. In tumor relapses after previous surgeries or irradiation, the surgical options for reconstruction are extremely narrowed and is our opinion that microvascular autologous tissue transplantation is specially indicated in those patients, even though it requires a technically demanding procedure. Materials and Methods: We analyzed retrospectively all patients treated at our institution between March 2014 and December 2018 and that met all the inclusion criteria: 1) oncological surgery for a tumor involving the skull base; 2) previous surgical treatment for that tumor; 3) cranial base bone resection; 4) dural exposure or defect; 5) reconstruction done with a free flap. The patient's age, comorbidities, number of previous surgeries and/or irradiation, oncological excisional procedures, type of defect, type of reconstruction, postoperative complications and mortality were reviewed. Results: Fifteen flaps were used in the 14 patients that met all the inclusion criteria. The used flaps were: Anterolateral Thigh (ALT) perforator or chimeric ALT/Vastus Lateralis (VL) (n=6), profunda artery perforator (n=3), muscular Rectus Abdominis (n=2), Vertical Rectus Abdominis Myocutaneous (VRAM) (n=2), chimeric osteomuscular scapular tip/Latissimus Dorsi (LD) (n=1) and radial forearm (n=1). Dural defects were reconstructed with Pericranial or fascia Lata grafts in 7 patients. No total flap failures or vascular thrombotic events were noted and just one case of partial flap necrosis was registered (treated conservatively). There was one case of cerebrospinal fluid leakage, one diffuse cerebral edema and one donor site wound dehiscence, all successfully treated with conservative measures. The only complication that required a second operation was a cranioplasty prosthetic exposure that required a second free flap. One patient had a tracheostomy bleeding followed by a pneumothorax and died 8 weeks postoperatively with a nosocomial pneumonia. In the follow-up period, one patient died 19 months postoperatively with a local relapse and another with a metastatic disease (at month 15). Conclusion: Secondary or multiple relapsed cases in the skull base require reconstructions that are technically demanding and the defects are often extensive. The surgical options are extremely reduced by previous treatments and if the basic concepts of cranial base reconstruction were strictly respected, the microsurgical free flaps can offer the best chance to avoid severe complications. However, it is not without some postoperative complications and mortality can be significant in the follow-up because of the advanced stage of the oncologic disease.

Intracranial hemangiopericytoma: long-term surgical outcomes

BACKGROUND: According to 2021 WHS Classification, intracranial hemangiopericytomas or solitary fibrous tumors are rare meningeal neoplasms involving blood vessels and soft tissues. Such neoplasms are commonly classified as malignant due to their aggressive growth, metastasizing beyond the cranial cavity, and frequent recurrencies. Since these tumors rarely occur in neurosurgical patients, publications in Russian do not cover big cohorts of patients whose conditions would be assessed during both early and late observation periods.&#x0D; AIM: The present study analyzed our experience in surgical treatment of hemangiopericytomas and its long-term results.&#x0D; METHODS: The study was arranged as a single-center, pro-and retrospective trial that included hemangiopericytomas patients (n=17), whose tumors of different grades of malignancy (13) were operated at the Federal Neurosurgical Center in Novosibirsk from 2013 to 2021. The follow-up estimates included survivability; physical status (Karnofskys Scale); radicality; metastatic foci; need for postoperative chemo-and radiation therapy; adjuvant therapy effect on patients survivability, and delaying time to relapse.&#x0D; RESULTS: In total, 17 patients were included. 11 of them underwent total hemangiopericytomas removal (65%), and 6 subtotal removal (35%). Their survivability within the first year after the operation was 100%. As for the 5-year follow up, only 8 patients out of 17 were available, their mean observation time comprising 64.7 months. The 5-year survivability was 75% (6 out of 8 patients). A relapse occured in 3 out of 17 (17.5%). The mean delaying time comprised 67 months. 6 out of 17 patients (35%) underwent radiation therapy. Among the patients with total and subtotal removals who underwent postoperative radiation treatment neither a relapse nor tumor growth nor metastases were found.&#x0D; CONCLUSION: Intracranial hemangiopericytoma is a rare malignant space-occupying neoplasm. Considering our experience and published data, its treatment requires aggressive tactics that includes a radical removal of the tumor followed by early irradiation of the tumors residual volume or bed either in a proton accelerator or a gamma-knife facility notwithstanding its malignancy grade. It is also recommended to extend the follow-up period for such patients to 1015 years that should include annual cancer screening to detect local relapses and metastases.

Detection and Differentiation of Local Recurrence of Soft Tissue Sarcoma against the Background of Postoperative Changes Using Echography

Introduction: Early detection of relapses of soft tissue sarcoma can reduce the risk of reoperation and improve oncological outcomes.Material and methods: A multimodal ultrasound examination of 108 soft tissue sites of different localizations was performed, in which earlier (with an interval of 12–62 months after the previous operation) malignant tumors of different histological affiliation were removed.Results: In 37 (34.3 %) observations against the background of postoperative changes, local relapses of neoplasms were revealed. Echographic symptoms that allow differentiating tumor growth and imitating its non-tumor changes have been determined.Conclusions: The most reliable manifestation of the recurrence of the tumor process is a local, uneven strengthening of the vascular pattern directly behind the contour of the neoplasm in its immediate tissue environment.

An Analysis of Patients Treated with Stereotactic Body Radiotherapy for Metastatic Urinary Tract Tumors to Identify Predictors of Response.

To identify selection criteria linked to outcomes in patients treated with stereotactic body radiotherapy (SBRT) for metastatic tumors of the urinary tract (UT). Single institution retrospective analysis of SBRT treated patients for oligometastatic/progressive UT tumors from 2006-2022. Charts were queried for M1 status at diagnosis or during disease course, treatment details (surgery, SBRT, systemic therapy), metabolic status (diabetes [DM], BMI) and outcomes. A linear quadratic formula was used to calculate the biologically effective dose (BED) using an α/β of 10 for tumor. Descriptive statistics portrayed the cohort, and analyses were done at patient and site level. Time-to-event analyses, including overall survival (OS) and progression-free survival (PFS) from SBRT, were assessed by the Kaplan-Meier method. Cox regression was used for univariable (UVA) and multivariable analyses (MVA) to identify predictors of outcomes. A total of 35 patients were treated at 44 metastatic sites, including: bone (25%), node (36.4%), lung (20.5%), soft tissue (13.6%) and liver (4.5%). Most were male (74.3%) with a median age of 70 (range: 51-89), without DM (60%) having a median BMI of 29.8, and ECOG <2 (97.1%) at time of SBRT. Six (17.1%) patients were M1 at diagnosis. Of the 29 non-M1 patients, 86.2% received definitive local therapy (LT), 58.6% had at least T3/N+ disease, 75.8% received systemic therapy with a median of 2 agents (range: 1-6) prior to SBRT. Sixteen (45.7%) received immunotherapy (IO) with most receiving this before (75%) and after (56.2%) SBRT. Six patients had positive PD-L1 status (n = 10). The median RT dose, fractionation and BED was 40 Gy (range: 14-46), 5 fractions, and 72 (range: 28-132), respectively. At a median follow-up of 34.8, the median OS was 18.4 m (range: 9.3-27.4) with a 2-year OS of 35.9%. At patient level, 62.8% recurred after SBRT. The median PFS after SBRT was 5.3 m (range: 1.8-8.7) with a 2-yr PFS of 29.3%. Patient-level PFS was improved with LT (6.7 vs 1.4 m; p = 0.001) and DM (NR vs 2.9 m; p = 0.015), whereas improved OS was related with LT (18.9 vs 6.6 m; p = 0.03), DM (p = 0.04), ECOG (p = 0.004), and no relapse after SBRT (NR vs 9.8 m; p <0.001). Exposure to < 3 systemic agents prior to SBRT portended better PFS (6.7 vs 2.6 m; p = 0.04) without any impact by IO. At site level, 20.4% of sites had local relapse with 4 being the first event. Site was related with PFS (p = 0.009) with order of increased relapse risk being liver > bone > soft tissue > node > lung. No dosimetric feature was related with recurrence risk. On MVA, both DM (p = 0.02) and LT (p = 0.002) were predictive for PFS. Only recurrence after SBRT predicted for OS on MVA (HR: 6.7, 95% CI: 1.4-31; p = 0.014). In the IO subset, median PFS was 5.3 m and OS was 9.4 m, with no difference seen with IO-SBRT sequence or PDL1 status. Optimized selection criteria for metastasis-directed therapy in patients with UT tumors is unclear, notably with IO. Future studies may benefit by assessing circulating tumor markers prior to SBRT.

Oncology

The October 2023 Oncology Roundup360 looks at: Are pathological fractures in patients with osteosarcoma associated with worse survival outcomes?; Spotting the difference: how secondary osteosarcoma manifests in retinoblastoma survivors versus conventional cases; Accuracy of MRI scans in predicting intra-articular joint involvement in high-grade sarcomas around the knee; Endoprosthetic reconstruction for lower extremity soft-tissue sarcomas with bone involvement; Local relapse of soft-tissue sarcoma of the extremities or trunk wall operated on with wide margins without radiation therapy; 3D-printed, custom-made prostheses in patients who had resection of tumours of the hand and foot; Long-term follow-up for low-grade chondrosarcoma; Evaluation of local recurrence and diagnostic discordance in chondrosarcoma patients undergoing preoperative biopsy; Radiological scoring and resection grade for intraosseous chondrosarcoma.