Radiological Response Research Articles

Sensing Biomolecules Associated with Cells' Radiosusceptibility by Advanced Micro- and Nanospectroscopy Techniques.

Radiotherapy is one of the most common approaches for cancer treatment, especially in the case of peripheral nervous system tumors. As it requires exposure to high doses of ionizing radiation, it is important to look for substances that support efficient reduction of the tumor volume with simultaneous prevention of the surrounding noncancerous cells. Cannabidiol (CBD), which exhibits both anticancer and neuroprotective properties, was applied as a potential modulator of radiological response; however, its influence on cells undergoing irradiation remains elusive. Here, we have applied high-resolution optical spectroscopy techniques to capture biomolecules associated with CBD shielding of normal and damaging cancerous cells upon X-ray exposure. Conventional Raman (RS) and Fourier transformed infrared (FT-IR) spectroscopies provided semiquantitative information mainly about changes in the concentration of total lipids, DNA, cholesteryl esters, and phospholipids in cells. A through assessment of the single cells by atomic force microscopy coupled with infrared spectroscopy (AFM-IR) allowed us to determine not only the alterations in DNA content but also in its conformation due to cell treatment. Pronounced nanoscale changes in cholesteryl ester metabolites, associated with CBD treatment and radiation, were also observed. AFM-IR chemoselective maps of the single cells indicate the modified distribution of cholesteryl esters with 40 nm spatial resolution. Based on the obtained results, we propose a label-free and fast analytical method engaging optical spectroscopy to assess the mechanism of normal and cancerous cell susceptibility to ionizing radiation when pretreated with CBD.

Transarterial Radioembolization Can Downstage Intermediate and Advanced Hepatocellular Carcinoma to Liver Transplantation.

Transarterial radioembolization (TARE) is an effective treatment to control tumor growth and improve survival in hepatocellular carcinoma (HCC). The role of TARE in downstaging patients to liver transplantation (LT) is unclear. The aim of this study was to investigate the downstaging efficacy of TARE for intermediate and advanced HCC. Intention-to-treat analysis with multistate modeling was performed. Patients moved through 5 health states: (1) from TARE to listing, (2) from TARE to death without listing, (3) from listing to LT, (4) from listing to death without LT, and (5) from transplant to death. Factors affecting the chance of death after TARE were considered to stratify outcomes. Two hundred fourteen patients underwent TARE. Of those, 43.9% had radiological response, 29.9% were listed, and 22.8% were transplanted. The probability of being alive without LT was 40.5% 1 y after TARE and 11.5% at 5 y. The chance of being listed was 9.4% at 1 y and 0.9% at 5 y. The probability of dying after TARE without LT was 38% at 1 y and 73% at 5 y. The overall survival of patients receiving LT was 61% at 5 y after transplant. Tumor beyond up-to-seven criteria, alfafetoprotein >400 ng/mL, and albumin-bilirubin ≥2 were associated with death. Three risk groups were associated with different response, chances of being listed, and receiving LT. Median survival was 3 y for low-risk, 1.9 y for intermediate-risk, and 9 mo for high-risk patients (P < 0.001). In intermediate and advanced HCC, TARE allows for a 44% chance of response, 30% downstaging, and 23% probability of permitting LT. Patient's and tumor's characteristics allow for risk stratification and predict survival from TARE.

FP2.1 - The accuracy of radiological staging in rectal cancer patients post-long course chemoradiotherapy treatment

Abstract Aim Accurate post Long-course chemoradiotherapy treatment (LCCRT) allows safe selection of patients to rectal preservation without delaying resection in those with residual cancer. The aim of this study was to assess the accuracy of radiological staging in these patients. Methods Demographic and treatment data from consecutive patients receiving LCCRT for rectal cancer between May 2020 to December 2021 was collected. Local radiological staging post-LCCRT treatment was compared to pathological staging. Where patients had complete radiological response (CRR) and opted for watch and wait (WW) those with demonstrable local recurrence, within 12 months, were assumed to have been under-staged. Results Of 61 patients, 37 underwent surgical resection following LCCRT and 24 watch and wait for CRR. Post-LCCRT imaging was taken at a median of 10.86 weeks (IQR, 8.86- 13.00) post completion of treatment and resections 16.57 weeks (IQR 9.71 – 23.00) post-imaging. Four WW patients were diagnosed with local recurrence at a median of 56.54 weeks of follow-up (IQR, 39.9 – 67.90). The ratio of patients radiologically staged as T0:T1:T2:T3:T4 was 15%: 0%: 28%: 46%: 10%; whilst the pathology specimens demonstrated 20%: 5%: 12%: 49%: 15% respectively. Nodal staging (N0:N1:N2) was 78%: 20%: 2% with histology showing 71%: 24%: 5% respectively. Conclusion In our low-numbered study T-staging of patients with T0 and T1 disease had highest rates of over-staging such that 2 (5%) patients for potential watch and wait were not recognised as CCR by MRI alone. Nodal staging appeared more accurate although a tendency to under-stage N0 disease was seen.

Neoadjuvant immune checkpoint blockade in women with mismatch repair deficient endometrial cancer: a phase I study

Neoadjuvant immune checkpoint blockade (ICB) has shown unprecedented activity in mismatch repair deficient (MMRd) colorectal cancers, but its effectiveness in MMRd endometrial cancer (EC) remains unknown. In this investigator-driven, phase I, feasibility study (NCT04262089), 10 women with MMRd EC of any grade, planned for primary surgery, received two cycles of neoadjuvant pembrolizumab (200 mg IV) every three weeks. A pathologic response (primary objective) was observed in 5/10 patients, with 2 patients showing a major pathologic response. No patient achieved a complete pathologic response. A partial radiologic response (secondary objective) was observed in 3/10 patients, 5/10 patients had stable disease and 2/10 patients were non-evaluable on magnetic resonance imaging. All patients completed treatment without severe toxicity (exploratory objective). At median duration of follow-up of 22.5 months, two non-responders experienced disease recurrence. In-depth analysis of the loco-regional and systemic immune response (predefined exploratory objective) showed that monoclonal T cell expansion significantly correlated with treatment response. Tumour-draining lymph nodes displayed clonal overlap with intra-tumoural T cell expansion. All pre-specified endpoints, efficacy in terms of pathologic response as primary endpoint, radiologic response as secondary outcome and safety and tolerability as exploratory endpoint, were reached. Neoadjuvant ICB with pembrolizumab proved safe and induced pathologic, radiologic, and immunologic responses in MMRd EC, warranting further exploration of extended neoadjuvant treatment.

The Relationship between Treatment Response and Overall Survival in Borderline, Non-Resectable and Resectable Pancreatic Cancer Patients Treated with Neoadjuvant FOLFIRINOX.

Background: The National Comprehensive Cancer Network (NCCN)-recommended treatment for patients with borderline-resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC) involves a combination of neoadjuvant FOLFIRINOX chemotherapy and the curative surgical resection of the tumor. This study seeks to identify the clinical, radiological, laboratory, and pathologic predictors that can anticipate the oncological outcomes of patients. Methods: In this study, we conducted a retrospective analysis of patients who had undergone curative surgical resection for BRPC, LAPC, or resectable disease with high-risk features after receiving neoadjuvant FOLFIRINOX at two institutions. We evaluated by means of multivariate analysis whether clinical and laboratory response, tumor markers, radiological response, and pathologic tumor response grade correlated with overall survival (OS) and disease-free survival (DFS). Results: The study enrolled a total of 70 patients with BRPC, LAPC, and resectable disease with high-risk features who underwent resection after neoadjuvant FOLFIRINOX. Age above 65 years and fewer than nine cycles of chemotherapy (OR 4.2; 95% CI 1.4-12.0; p-value 0.007); locally advanced tumors after neoadjuvant treatment (NAT) (OR 7.0; 95% CI 1.9-25.7; p-value 0.003); and lymph node disease and histological tumor regression grade 2 and 3 (OR 4.3; 95% CI 0.9-19.2; p-value 0.05) were risk factors linked to adverse OS and DFS. The median OS and DFS were 33 (22-43.9) months and 16.5 (11.3-21.6) months, respectively. Conclusions: Classification as a LA tumor after NAT was the only preoperative radiological factor that predicted adverse survival in patients undergoing curative surgery after NAT. Other clinical, biochemical, and radiological measures of response were not found to predict OS. Patient age, the cumulative administration of more than eight cycles of chemotherapy, and a significant pathological response were associated with better OS. The results of this study are important for treatment decision-making and prognostication in patients with BRPC and LAPC.

Evaluating Saudi Arabian nurses' willingness to respond to nuclear and radiological disasters.

We evaluated Saudi Arabian nurses' willingness to engage in nuclear and radiological disaster response. In the face of rising nuclear and radiological threats, it is essential that nurses are fully prepared to handle the health consequences of such emergencies. As frontline responders, nurses play a critical role in managing high-stakes situations, making their readiness a key factor in ensuring public safety during these crises. A cross-sectional survey was conducted among 612 registered nurses in Saudi Arabia. The survey used a structured questionnaire based on the theory of planned behavior, identifying behavioral intentions as the primary outcome and attitudes toward these behaviors, subjective norms, and perceived behavioral control as influencing factors. The data were analyzed using descriptive and inferential statistics. Most respondents lacked specialized training and reported strong behavioral intentions. Attitude and perceived behavioral control were key drivers of these behavioral intentions, with less impact from subjective norms. Behavioral intentions were also shaped by education, the perceived likelihood of nuclear and radiological emergencies in their region, peer influence, perceived self-efficacy, and family concerns. Younger and married nurses showed significantly stronger behavioral intentions. Although most nurses lacked specialized training, their strong engagement intentions and positive responses to active learning and training indicate a desire to close this gap through further education. However, inadequate institutional support, trouble communicating with family, and concerns about personal radiation exposure emerged as potential barriers. Targeted educational initiatives and support systems are needed to enhance nurses' confidence, competence, and willingness to engage in radiological and nuclear emergency scenarios. Policymakers should prioritize the development of specialized training programs and support mechanisms for nurses, ensuring they are adequately prepared to respond effectively to increasing radiological and nuclear threats.

Rationale and Design of the COPERNIC Trial: A Study of On-treatment ctDNA Changes in Chemo-refractory Colorectal Cancer Patients

BackgroundEvidence suggests that ctDNA may be a reliable biomarker to monitor metastatic colorectal cancer (CRC) evolution. Nevertheless, evidence on the potential of liquid biopsy in this setting is still low quality, mostly consisting of retrospective studies. MethodsCOPERNIC is an international, multicenter clinical trial. The pilot study aims to confirm the predictive potential of early on-treatment ctDNA dynamics, and inform the design of a larger ctDNA-driven trial. Advanced CRC patients who are candidates for ≥3rd lines of systemic therapy undergo longitudinal blood sample collection during treatment (day 1, 15 and 29 for 2- or 4-weekly treatment regimens; day 1, 22 and 43 for 3-weekly treatment regimens) and at each imaging assessment. ctDNA analyses are carried out with the FoundationOne Liquid CDx and FoundationOneMonitor assays, and ctDNA changes during treatment are correlated with radiologic response (as assessed every 8-12 weeks by RECIST v1.1). The primary objective is to select the optimal timepoint and cut-off value for early ctDNA changes (at day 15/22) to predict progressive disease as best radiological response with a high positive predictive value. The cut-off value for ctDNA will be defined based on nonparametric ROC-curves with bootstrapping. Based on the expected rate of progressive disease and statistical assumptions, 109 patients are needed to be screened to have 87 assessable patients. COPERNIC is sponsored by the Institut Jules Bordet, and supported by Roche and Foundation Medicine. Recruitment is open in 13 centres across Belgium and France. The study is registered with clinicaltrials.gov (NCT05487248).

Comparison of drug-eluting bead with conventional transcatheter arterial chemoembolization for hepatocellular carcinoma with portal vein tumor thrombus: a randomized clinical trial.

Drug-eluting bead transarterial chemoembolization (DEB-TACE) has shown efficacy for treating hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). However, whether DEB-TACE is superior to conventional TACE (cTACE) remains unclear. This randomized controlled trial aimed to compare the efficacy and safety of DEB-TACE versus cTACE in treating HCC with PVTT. The study was conducted at a tertiary care center in Southeast China. HCC patients with PVTT were randomized at a 1:1 ratio into the DEB-TACE or cTACE groups. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS) and the incidence of adverse events (AEs). An independent review committee assessed the radiologic response according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST). AEs were assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Systemic therapies were not restricted. Between September 2018 and July 2020, 163 patients were randomized to undergo DEB-TACE ( n =82) or cTACE ( n =81). Nine patients were excluded, and 154 patients were included in the final analysis; the median age was 55 years (range, 24-78years), and 140 (90.9%) were male. The median PFS in the DEB-TACE group was 6.0 months (95% CI, 5.0-10.0) versus 4.0 months (95% CI, 3.0-5.0) in the cTACE group (hazard ratio, 0.63; 95% CI, 0.42-0.95; P =0.027). The DEB-TACE group showed a higher response rate [51 (66.2%) vs. 36 (46.8%); P =0.0015] and a longer median OS [12.0 months (95% CI, 9.0-16.0) vs. 8.0 months (95% CI, 7.0-11.0), P =0.039] than the cTACE group. Multivariate analysis showed that the treatment group, ALBI score, distant metastasis and additional TKIs were the four independent prognostic factors correlated with PFS. In addition, the treatment group, PVTT group and combination with surgery were independently associated with OS. AEs were similar in the two groups, and postembolization syndrome was the most frequent AE. DEB-TACE is superior to cTACE in treating HCC patients with PVTT, demonstrating improved PFS and OS with an acceptable safety profile, and may thus emerge as a promising treatment strategy for HCC patients with PVTT. Chinese Clinical Trial Registry ChiCTR1800018035.

A review of sonodynamic therapy for brain tumors.

Sonodynamic therapy (SDT) is gaining attention as a promising new noninvasive brain tumor treatment that targets and selectively kills tumor cells, with limited side effects. This review examines the mechanisms of SDT and ongoing clinical trials looking at optimization of sonication parameters for potential treatment of glioblastoma (GBM) and diffuse intrinsic pontine glioma (DIPG). The results in the first patient with recurrent GBM treated at the Mayo Clinic are briefly discussed. The authors of this literature review used electronic databases including PubMed, EMBASE, and OVID. Articles reporting relevant preclinical and clinical trials were identified by searching for text words/phrases and MeSH terms, including the following: "sonodynamic therapy," "SDT," "focused ultrasound," "5-ALA," "ALA," "brain tumors," "diffuse pontine glioma," "glioblastoma," and "high grade glioma." Preclinical and clinical trials investigating the specific use of SDT in brain tumors were reviewed. In preclinical models of high-grade glioma and GBM, SDT has shown evidence of targeted tumor cell death via the production of reactive oxygen species. Emerging clinical trial results within recurrent GBM and DIPG show evidence of successful treatment response, with minimal side effects experienced by recruited patients. So far, SDT has been shown to be a promising noninvasive cancer treatment that is well tolerated by patients. The authors present pilot data suggesting good radiological response of GBM to a single SDT treatment, with unpublished observation of a lack of off-target effects even after multiple (monthly) sonication outpatient treatments. The scope of the clinical trials of SDT is to investigate whether it can be the means by which the fatal diagnosis of GBM or DIPG is converted into that of a chronic, treatable disease. SDT is safe, repeatable, and better tolerated than both chemotherapy and radiotherapy. It has been shown to have an effect in human cancer therapy, but more clinical trials are needed to establish standardized protocols for sonosensitizer delivery, treatment parameters, and combination therapies. The most appropriate timing of treatment also remains to be determined-whether to prevent recurrence in the postoperative period, or as a salvage option in patients with recurrent GBM for which redo surgery is inappropriate. It is hoped that SDT will also be developed for a wider spectrum of clinical indications, such as metastases, meningioma, and low-grade glioma. Further clinical trials are in preparation.

Therapeutical Usefulness of PD-1/PD-L1 Inhibitors in Aggressive or Metastatic Pituitary Tumours.

Therapeutic options for pituitary neuroendocrine tumours (PitNETs) refractory to temozolomide are scarce. Immune checkpoint inhibitors (ICIs), particularly inhibitors of the programmed cell death-1 (PD-1) pathway and its ligand (PD-L1), have been experimentally used in aggressive or metastatic PitNETs. We aimed to study the therapeutic usefulness of anti-PD-1 drugs in patients with aggressive or metastatic PitNETs. Published cases and case series involving patients with PitNETs treated with PD-1/PD-L1 inhibitors were reviewed. Demographic data, clinical-pathological features, previous therapies, drug dosage and posology, and the best radiological and biochemical responses, as well as survival data, were evaluated. We identified 29 cases of aggressive (n = 13) or metastatic (n = 16) PitNETs treated with PD-1/PD-L1 inhibitors. The hypersecretion of adrenocorticotropic hormone (ACTH) was documented in eighteen cases (62.1%), seven were prolactinomas (24.1%), and four were non-functioning PitNETs. All patients underwent various therapies prior to using ICIs. Overall, a positive radiological response (i.e., partial/complete radiological response and stable disease) was observed in eighteen of twenty-nine cases (62.1%), of which ten and four were ACTH- and prolactin-secreting PitNETs, respectively. Hormonal levels reduced or stabilised after using ICIs in 11 of the 17 functioning PitNET cases with available data (64.7%). The median survival of patients treated with ICIs was 13 months, with a maximum of 42 months in two ACTH-secreting tumours. Among 29 patients with PitNETs treated with PD-1/PD-L1 inhibitors, the positive radiological and biochemical response rates were 62.1% and 64.7%, respectively. Altogether, these data suggest a promising role of ICIs in patients with aggressive or metastatic PitNETs refractory to other treatment modalities.

Neoadjuvant 177Lu-DOTATATE for non-functioning pancreatic neuroendocrine tumours (NEOLUPANET): multicentre phase II study.

Resection of non-functioning pancreatic neuroendocrine tumours (NF-PanNETs) is curative in most patients. The potential benefits of neoadjuvant treatments have, however, never been explored. The primary aim of this study was to evaluate the safety of neoadjuvant 177Lu-labelled DOTA0-octreotate (177Lu-DOTATATE) followed by surgery in patients with NF-PanNETs. NEOLUPANET was a multicentre, single-arm, phase II trial of patients with sporadic, resectable or potentially resectable NF-PanNETs at high-risk of recurrence; those with positive 68Ga-labelled DOTA PET were eligible. All patients were candidates for neoadjuvant 177Lu-DOTATATE followed by surgery. A sample size of 30 patients was calculated to test postoperative complication rates against predefined cut-offs. The primary endpoint was safety, reflected by postoperative morbidity and mortality within 90 days. Secondary endpoints included rate of objective radiological response and quality of life. From March 2020 to February 2023, 31 patients were enrolled, of whom 26 completed 4 cycles of 177Lu-DOTATATE. A partial radiological response was observed in 18 of 31 patients, and 13 patients had stable disease. Disease progression was not observed. Twenty-four R0 resections and 4 R1 resections were performed in 29 patients who underwent surgery. One tumour was unresectable owing to vascular involvement. There was no postoperative death. Postoperative complications occurred in 21 of 29 patients. Severe complications were observed in seven patients. Quality of life remained stable after 177Lu-DOTATATE and decreased after surgery. Neoadjuvant treatment with 177Lu-DOTATATE is safe and effective for patients with NF-PanNETs.

Real-world efficacy and safety of durvalumab-tremelimumab as second-line systemic therapy after atezolizumab-bevacizumab in unresectable hepatocellular carcinoma.

The efficacy and safety of immune-checkpoint inhibitors (ICI) for the treatment of unresectable hepatocellular carcinoma are known. We explored ICI rechallenges with direct switching from 1 ICI regimen to another. This retrospective study included 16 patients who received atezolizumab-bevacizumab (Atezo+Bev) and durvalumab-tremelimumab (Dur+Tre) as the first-line and second-line combination therapy, respectively, at Hiroshima University Hospital. The radiological response and adverse event were evaluated in all patients. Of the 16 patients, 12 were male, and the median age at Atezo+Bev induction was 71 years. The reasons for medication changes were disease progression in 11 patients and adverse events in 5 patients. With Atezo+Bev and Dur+Tre initiation, the Barcelona-Clinic Liver-Cancer stage (A/B/C) progressed in 9/6/3 and 3/4/9 patients and the Child-Pugh classification (A/B/C) progressed in 12/4/0 and 9/6/3 patients, respectively. The disease control rate and overall response rate of Atezo+Bev were 87.5% and 58.3%, respectively, and of Dur+Tre were 62.5% and 0%, respectively. The most common immune-related adverse event in both the Atezo+Bev and Dur+Tre groups was colitis; 3 of the 5 patients with colitis on Atezo+Bev treatment had colitis with Dur+Tre, and 2 had exacerbations. Regarding liver function, ALBI score significantly decreased during Atezo+Bev, but not Dur+Tre, treatment. In patients with colitis following Atezo+Bev, subsequent Dur+Tre treatment may induce colitis recurrence or exacerbation. For immune-related adverse events other than colitis, Dur+Tre could provide relatively safe disease control while maintaining liver function.

Focused ultrasound and concurrent chemotherapy for the treatment of advanced pancreatic cancer: A systematic review.

The combination of focused ultrasound (FUS) and chemotherapy is a novel treatment for pancreatic cancer. This paper reviews the literature on this combined therapy. The medical literature was searched according to PRISMA guidelines. Inclusion criteria were any study of patients with pancreatic cancer undergoing treatment with FUS and chemotherapy. Data extracted included stage, radiologic response, resection rate, survival, and adverse events. The initial search yielded 212 citations; 10 studies met inclusion criteria (9 retrospective cohorts; 1 randomized trial). A total of 631 patients received FUS + chemotherapy; 63.6% being stage 4, and 29.7% stage 3. Patient selection, FUS parameters, and chemotherapy used were all heterogeneous. Overall survival ranged from 7.4 to 21.6 months, radiologic response rate was 44.1%, and 24.4% of stage 3 patients underwent resection. All four studies with a comparison group demonstrated improved survival. FUS + chemotherapy decreased pain in 69.7% of patients. Severe adverse events occurred in 0.65%. The literature on combined FUS and chemotherapy for pancreatic cancer is heterogeneous. There is good evidence that adverse events are low, and that it provides effective palliation. There is evidence to suggest oncologic benefit, however, this is subject to selection bias and prospective trials are needed.

A gut microbiota rheostat forecasts responsiveness to PD-L1 and VEGF blockade in mesothelioma

Malignant mesothelioma is a rare tumour caused by asbestos exposure that originates mainly from the pleural lining or the peritoneum. Treatment options are limited, and the prognosis is dismal. Although immune checkpoint blockade (ICB) can improve survival outcomes, the determinants of responsiveness remain elusive. Here, we report the outcomes of a multi-centre phase II clinical trial (MiST4, NCT03654833) evaluating atezolizumab and bevacizumab (AtzBev) in patients with relapsed mesothelioma. We also use tumour tissue and gut microbiome sequencing, as well as tumour spatial immunophenotyping to identify factors associated with treatment response. MIST4 met its primary endpoint with 50% 12-week disease control, and the treatment was tolerable. Aneuploidy, notably uniparental disomy (UPD), homologous recombination deficiency (HRD), epithelial-mesenchymal transition and inflammation with CD68+ monocytes were identified as tumour-intrinsic resistance factors. The log-ratio of gut-resident microbial genera positively correlated with radiological response to AtzBev and CD8+ T cell infiltration, but was inversely correlated with UPD, HRD and tumour infiltration by CD68+ monocytes. In summary, a model is proposed in which both intrinsic and extrinsic determinants in mesothelioma cooperate to modify the tumour microenvironment and confer clinical sensitivity to AtzBev. Gut microbiota represent a potentially modifiable factor with potential to improve immunotherapy outcomes for individuals with this cancer of unmet need.

Radiological evaluation of response in patients with locally advanced/metastatic soft tissue sarcoma treated with trabectedin.

Background: Trabectedin is an antineoplastic drug approved for patients (pts) with advanced soft tissue sarcomas (STS). Interestingly, the radiological evaluation of response during trabectedin therapy is peculiar. Methods: The aim of this single-center retrospective study is to analyze the concordance of response assessment according to RECIST compared with Choi criteria in patients with STS treated with trabectedin between 2009 and 2020 at Regina Elena National Cancer Institute in Rome. Results: We present the preliminary data collected in the last 2months (mos) on 37pts who received the diagnosis between 2015 and 2020, with a median age of 52.5years (range 32-78). The median number of trabectedin cycles administered was four (range 2-50) for a median follow up of 5.83months (range 1-60). Histological subtypes of STS were five (13.5%) leiomyosarcoma, 14 (37.8%) liposarcoma, nine (24.3%) undifferentiated pleomorphic sarcoma, three (8.1%) synovial sarcoma, and six (16.2%) other rare histological subtypes. Eight pts (21.6%) received trabectedin in the first line setting, 21 (56.8%) in the second line, and seven (18.9%) received it in subsequent lines. One pt received trabectedin as neoadjuvant therapy in a clinical trial (ISG-STS 1001). Median progression-free survival was 3.6months (CI95% 2.7-4.6); median overall survival was 34.3months (CI95% 0-75.4). The radiological responses were evaluated with both RECIST and Choi criteria; responses matched in 33pts (89.2%) but not in four (10.8%). The best responses obtained according to RECIST criteria were two (5.4%) partial response (PR), 13 (35.1%) stable disease (SD), and 22 (59.5%) progressive disease (PD). Instead, two (5.4%), 13 (35.1%), and 22 (59.5%) pts obtained PR, SD, and PD respectively, according to Choi criteria. Cohen's kappa coefficient of concordance was 0.792 (p-value <0.002). A specialized radiologist performed all imaging examinations using a dedicated workstation in the same center. Conclusion: In this first analysis, the concordance between RECIST and Choi assessments demonstrates no statistically significant difference. Responses did not match for four pts. We are expanding the analysis to all pts included in the original cohort to confirm or deny these initial results.

Myeloid sarcoma, spectrum of clinical characteristics, prognostic impact, and treatment outcome

BackgroundAcute leukemia may present with extramedullary (EM) tissues. Myeloid sarcoma (MS) and leukemia cutis (LC) are considered extramedullary diseases. This study aims to evaluate the incidence, clinical characteristics, and prognostic factors affecting the outcome of pediatric patients with myeloid sarcoma at the pediatric oncology center from July 2007 to December 2017. Radiological imaging was used to stage the tumor, biopsy was done for pathological diagnosis, and bone marrow aspirate for morphology, flow cytometry, cytogenetics, and molecular analysis. Patients received chemotherapy protocols based on those used by the Children's Cancer Group for acute myeloid leukemia (AML).ResultThe study included 91 (13.2%) of 687 pediatric patients with acute myeloid leukemia, with a male-to-female ratio of 1.9 to 1. Prognostic factors that improved the patient’s 5-year overall survival (OS) were age > 5 years old, molecular and cytogenetic detection of t (8; 21), inv 16, presence of a single and small size lesion < 5 cm, negative CNS lesion, and achieved radiological response in isolated disease or radiological and marrow complete remission in disseminated disease post induction 1 with significant P value. Relapse, particularly early relapse, worsens the OS and EFS by 10% and 7.7%, respectively.ConclusionPatients over five with low-risk disease based on cytogenetics, a small, single, negative CNS lesion, and a complete response post induction 1 had better outcomes, with no significant difference between those with isolated extramedullary disease and those with marrow dissemination. Early relapse harms the outcome. The study group’s 5-year OS and EFS rates are 51.4% and 49.4%, respectively.

Viscoelastic properties of colorectal liver metastases reflect tumour cell viability

BackgroundColorectal cancer is the third most common tumour entity in the world and up to 50% of the patients develop liver metastases (CRLM) within five years. To improve and personalize therapeutic strategies, new diagnostic tools are urgently needed. For instance, biomechanical tumour properties measured by magnetic resonance elastography (MRE) could be implemented as such a diagnostic tool. We postulate that ex vivo MRE combined with histological and radiological evaluation of CRLM could provide biomechanics-based diagnostic markers for cell viability in tumours.Methods34 CRLM specimens from patients who had undergone hepatic resection were studied using ex vivo MRE in a frequency range from 500 Hz to 5300 Hz with increments of 400 Hz. Single frequency evaluation of shear wave speed and wave penetration rate as proxies for stiffness and viscosity was performed, along with rheological model fitting based on the spring-pot model and powerlaw exponent α, ranging between 0 (complete solid behaviour) and 1 (complete fluid behaviour). For histological analysis, samples were stained with H&E and categorized according to the degree of regression. Quantitative histologic analysis was performed to analyse nucleus size, aspect ratio, and density. Radiological response was assessed according to RECIST-criteria.ResultsFive samples showed major response to chemotherapy, six samples partial response and 23 samples no response. For higher frequencies (> 2100 Hz), shear wave speed correlated significantly with the degree of regression (p ≤ 0.05) indicating stiffer properties with less viable tumour cells. Correspondingly, rheological analysis of α revealed more elastic-solid tissue properties at low cell viability and major response (α = 0.43 IQR 0.36, 0.47) than at higher cell viability and no response (α = 0.51 IQR 0.48, 0.55; p = 0.03). Quantitative histological analysis showed a decreased nuclear area and density as well as a higher nuclear aspect ratio in patients with major response to treatment compared to patients with no response (all p < 0.05).DiscussionOur results suggest that MRE could be useful in the characterization of biomechanical property changes associated with cell viability in CRLM. In the future, MRE could be applied in clinical diagnosis to support individually tailored therapy plans for patients with CRLM.

Clinical characteristics and outcomes in patients with early-onset locally advanced rectal cancer.

70 Background: Despite a reduction in both the incidence and mortality of CRC in the elderly population, recent studies have highlighted an increase in the incidence of early-onset CRC (EO-CRC). Clinical and prognostic data in this context are limited and conflicting. The aim of our study was to evaluate the clinical differences and outcomes of patients with early onset locally advanced rectal cancer. Methods: We retrospectively collected data from 305 patients affected by LARC treated in Italy at the Medical Oncology Units of the University Hospital of Cagliari, Istituto Nazionale dei Tumori Milan, and AOU Ospedali Riuniti Ancona. All patients underwent neoadjuvant chemoradiotherapy. The primary objective was overall survival (OS) while while secondary objectives were overall response rate (ORR) and major TRG. Results: Twenty five (8,2%) pts were EO-RC and 280 (91,8%) were LO-RC. In EO-RC the locations were distributed as follows: 9 (36%) lower rectum, 13 (52%) medium rectum, and 3 (12%) upper rectum. Pathologic responses were as follows: 3 (12%) TRG-0, 6 (24%) TRG-1, 10 (40%) TRG-2, and 6 (24%) TRG-3. While the radiological responses were as follows: 2 (8%) CR, 15 (60%) PR, 7 (28%) SD, and 1 (4%) PD. In LO-RC the locations were: 78 (27,8%) lower rectum, 153 (54,6%) medium rectum, and 49 (17,6%) upper rectum. Pathologic responses were as follows: 29 (10,4%) TRG-0, 60 (21,4%) TRG-1, 159 (56,8%) TRG-2, and 32 (11,4%) TRG-3. Radiological responses were as follows: 25 (8,9%) CR, 155 (61,4%) PR, 64 (22,9%) SD, and 19 (6,8%) PD. The 10 year overall survival was significantly higher in LO-RC patients compared to EO-CRC patients: 92.54% versus 70.83% (p = 0.0005). Conclusions: Compared to LO-RCs, EO-RC patients had more frequent low rectal tumors and higher rates of major pathological responses. Despite this, 10-year OS was found to be inferior in EO-RC. Further studies and insights will be necessary to better understand the biological and clinical characteristics of early-onset tumors.

Osimertinib-induced DNA resistance mutations in cerebrospinal fluid of EGFR mutated NSCLC patients developing leptomeningeal metastases: ORA-LM study.

Diagnosis and treatment of leptomeningeal metastases (LM) in epidermal growth factor receptor mutation positive (EGFRm+) NSCLC is challenging. We aimed to identify resistance mechanisms (RM) to osimertinib in cerebrospinal fluid (CSF) and plasma. EGFRm+ patients with new or progressive LM during osimertinib were enrolled. NGS Ampliseq was performed on DNA isolated from CSF. Patients were prescribed osimertinib dose escalation (DE, 160mg QD) following lumbar puncture. Clinical and radiological response was evaluated four weeks after osimertinib DE. Twenty-eight patients were included. The driver mutation was identified in 93% of CSF samples (n=26). Seven (27%) harbored ≥1 RM. Twenty-five patients (89%) were prescribed osimertinib DE. Four weeks afterwards, symptoms improved in five patients, stabilized in nine and worsened in eleven patients. Twenty-one (84%) patients underwent MR imaging. Four showed radiological improvement, fourteen stabilization, and three worsening. In 27% of patients an RM was found in CSF ctDNA, none of which are targetable at time of writing, and clinical efficacy of osimertinib DE seems limited. There is much to gain in diagnostic as well as therapeutic strategies in EGFRm+ NSCLC LM.

Real-life clinical benefit of oral metronomic cyclophosphamide administration in elderly and heavily pretreated epithelial ovarian cancer patients

PurposeOral metronomic cyclophosphamide (OMC) implicates the daily administration of low doses of chemotherapy. Its antitumor activity combined with an oral administration route and a good toxicity profile makes OMC an attractive option for heavily pretreated patients. We retrospectively evaluated OMC’s clinical benefit and objective response in recurrent ovarian cancer patients.MethodsThis is a retrospective observational study involving patients treated with OMC (50 mg daily) from 2017 to 2022 at the Academic Division Gynaecology, Mauriziano Hospital, Torino, Italy. Clinical benefit assessment included CA125 response, radiological response, and reported symptomatic improvement. Toxicities were reported using Common Terminology Criteria for Adverse Events version 5.0.ResultsThirty-eight patients (average age 72, range 49–88) were included. 90% had FIGO stage III/IV at diagnosis and 64% underwent ≥ 3 previous lines of chemotherapy. Before OMC, 79% had ECOG 1 or 2. 8.6% of patients had a partial response (PR), and 40% a stable disease (SD). Median duration of response was 7.4 months. After 3 months on OMC, 51% experienced symptom improvement, and 53.3% experienced Ca125 reduction or stabilization. 66.7% of patients older than 75 responded to treatment; in 40% of cases, responses lasted ≥ 6 months (p = 0.08). No G3-4 hematological toxicities occurred. Nausea and fatigue G1–G2 were reported in 5 (13%) and 13 (34%) cases, respectively.ConclusionOMC is a feasible therapeutic option for recurrent ovarian cancer, providing satisfying clinical responses with a good toxicity profile, even in elderly and heavily pretreated patients with a suboptimal performance status.