Diagnosis Of Solid Tumors Research Articles

Dose-expansion part of a phase 1b global study of E7386 in combination with lenvatinib (LEN) in patients (pts) with hepatocellular carcinoma (HCC) and other solid tumors including endometrial cancer (EC).

TPS3169 Background: E7386, a first-in-class anticancer agent, inhibits protein-protein interaction between β-catenin and the CREB-binding protein, thus modulating Wnt/β-catenin signaling. E7386 is being tested in combination with LEN in the open-label global phase 1b Study 102. The dose-escalation part of Study 102 determined the recommended dose of E7386 + LEN in pts with HCC and other solid tumors. Here we describe the ongoing dose-expansion part in pts with HCC or EC. Methods: Eligible pts ≥18 years old should have an ECOG PS of 0-1 and a confirmed diagnosis of advanced, unresectable, or recurrent solid tumor. Pts with HCC will have a Child-Pugh score of A and a categorization of BCLC Stage B (not amenable to locoregional therapy or refractory to locoregional therapy, and not amenable to a curative treatment) or Stage C. Pts with HCC should also have received 1 prior immuno-oncology (IO)-based regimen and have progressed on/after prior treatment with IO therapy. If ineligible for IO therapy, pts should not have received prior systemic therapy; pts who previously received LEN are ineligible. In the EC subpart, pts should have disease progression after receiving prior platinum-based chemotherapy (PBT) and an IO-based therapy for EC. Pts may have received 1 additional line of PBT if given in the neoadjuvant/adjuvant setting, but not exceeding 3 lines of therapies. Pts with EC who are ineligible for IO therapy may have received only 1 prior systemic therapy including PBT. Pts who have received prior LEN therapy will be eligible if they meet protocol-specified criteria. Pts with HCC (n≈60) will be randomized in a 2:1 ratio into 1 of 2 treatment arms and will receive either the combination E7386 + LEN or LEN monotherapy in 28-day cycles. E7386 will be administered at 100 mg BID in the combination arm and LEN will be administered QD at 8 mg (if body weight <60 kg) or 12 mg (if body weight ≥60 kg) in both arms. Pts with HCC will be stratified by geographical region (Western Europe and North America vs Japan vs other countries). Pts with EC (n≈30) will receive only the combination E7386 120 mg BID + LEN 14 mg QD. The expansion part of Study 102 aims to assess safety and tolerability (primary endpoints), and pharmacokinetics and preliminary efficacy (secondary endpoints), of E7386 in combination with LEN for pts with HCC and EC. Efficacy of LEN monotherapy will be assessed for HCC (secondary endpoint). Tumors will be assessed by investigator per RECIST v1.1 every 8 weeks from the date of the first dose. Adverse events will be monitored and recorded for up to 30 days after the last dose or until initiation of a new anticancer therapy, whichever occurs first. Study sites will include the United States, France, Republic of Korea, Japan, and Taiwan. As of February 5, 2024, 46 pts with HCC and 16 pts with EC have enrolled. Clinical trial information: NCT04008797 .

ICatalog: An open-source, collaborative platform for precision oncology studies.

10020 Background: Genomic profiling of patient (pt) tumors using next-generation sequencing (NGS) has become an integral part of precision oncology (PO). To address the need for a streamlined, interoperable approach to clinical and NGS data management, interpretation, and reporting for a multi-institution pediatric PO study we developed iCatalog (iCat), a clinical decision support system for a multi-institution pediatric PO study. Methods: iCat was developed by the University of Chicago (UChicago) and Dana-Farber Cancer Institute to create clinical interpretation reports for the iCat2/Genomic Assessment Informs Novel Therapy Consortium (GAIN) study. It is a web-based application using the Python Django framework using open-source software and runs on virtual machines (VM) behind a secure firewall. iCat manages user and administrative permissions according to role and site. It securely stores, manages, and integrates genomic and clinical information as well as internal and external genomic knowledge on a patient level. Data types available during interpretation and report generation include pt demographics, specimen-level information such as diagnosis from pathology reports, and molecular data. iCat can host molecular data from different NGS test types. These data are entered through web interfaces and API calls. Genomic knowledge accessible in iCat is a combination of information brought in from external resources and gene and variant-level pediatric-specific curations completed in iCat by curators. Editable study-specific patient reports are generated for each test. Results: As of January 10, 2024, iCat has generated reports for 902 tests and stores information for an additional 217 tests for the 742 pts enrolled in the GAIN study. Of the 217 tests, 25 tests have reports in progress and 192 tests had reports generated manually before iCat was developed. Genomic data are from 11 different test types and clinical data are from patients with 92 rare pediatric solid tumor diagnoses. A total of 108 pts have received iCat clinical interpretation reports integrating genomic data from more than one NGS test type. The knowledge base contains pediatric-specific research-team authored curations for 561 genes, 2114 unique SNVs, 268 unique CNVs, and 227 unique structural variants. Test-specific, variant-level therapeutic recommendations have been made on 666 reports for 502 pts. Diagnostic or hereditary risk associations have been made on 729 reports for 537 pts. Conclusions: iCat is an academically developed open-source platform for PO studies that integrates clinical and genomic data, supports gene and variant interpretation, and facilitates the generation of an individualized genomic report with relevant clinical information for treating physicians. We developed and tested iCat for a pediatric precision oncology study and propose it as a customizable, collaborative platform for future precision oncology research.

Instruments for Evaluating the Nutritional Status of Cancer Patients Undergoing Antineoplastic Treatment: A Scoping Review.

The use of validated tools to evaluate the nutritional status of the cancer patient provides guaranteed precision and reliability in their nutritional evaluation, ensuring that the information is accurate and reflects the patient's situation. The aim of this study was to identify the valid and reliable instruments in the evaluation of the nutritional status of cancer patients with a diagnosis of solid tumor undergoing antineoplastic treatment (chemotherapy and/or immunotherapy). A scoping review was conducted to search for original articles published in scientific journals in English, Spanish, or Portuguese in the past five years. In order to identify potentially relevant documents, searches were performed in the following databases: SCOPUS, WOS, CINAHL, MEDLINE, BVS, and PUBMED. DECS-MeSH descriptors and Boolean operators were used. In addition, the Arksey and O'Malley protocol, the Joanne Briggs Institute (JBI) method, and the flow chart of the Preferred Information Elements for Systematic Reviews and Meta-Analyses, known as PRISMA, were followed. The initial search strategy identified a total of 164 references, which were examined successively, leaving a final selection of ten studies. It was found that the most used instrument for nutritional evaluation was the Patient-Generated Subjective Global Assessment (PG-SGA). Other questionnaires also stood out such as the Mini Nutritional Assessment (MNA), the Malnutrition Universal Screening Tool (MUST), the Nutritional Risk Screening (NRS 2002), and the Functional Assessment of Anorexia/Cachexia Therapy (FAACT). The variation in the tools used ranges from subjective assessments to objective measurements, thus underlining the need for a comprehensive and individualized approach.

Nanomaterial-assisted oncolytic bacteria in solid tumor diagnosis and therapeutics.

Cancer presents a formidable challenge in modern medicine due to the intratumoral heterogeneity and the dynamic microenvironmental niche. Natural or genetically engineered oncolytic bacteria have always been hailed by scientists for their intrinsic tumor-targeting and oncolytic capacities. However, the immunogenicity and low toxicity inevitably constrain their application in clinical practice. When nanomaterials, characterized by distinctive physicochemical properties, are integrated with oncolytic bacteria, they achieve mutually complementary advantages and construct efficient and safe nanobiohybrids. In this review, we initially analyze the merits and drawbacks of conventional tumor therapeutic approaches, followed by a detailed examination of the precise oncolysis mechanisms employed by oncolytic bacteria. Subsequently, we focus on harnessing nanomaterial-assisted oncolytic bacteria (NAOB) to augment the effectiveness of tumor therapy and utilizing them as nanotheranostic agents for imaging-guided tumor treatment. Finally, by summarizing and analyzing the current deficiencies of NAOB, this review provides some innovative directions for developing nanobiohybrids, intending to infuse novel research concepts into the realm of solid tumor therapy.

Health-Related Quality of Life of Adolescent and Young Adult-Aged Childhood Cancer Survivors in a South African Cohort: A Pilot Study Using the Minneapolis-Manchester Quality of Life Instrument.

Purpose: We investigated the health-related quality of life (HRQoL) of an adolescent and young adult (AYA)-aged South African childhood cancer survivor (CCS) cohort. Methods: Participants completed the Minneapolis-Manchester Quality of Life adolescent and adult forms. The overall Cronbach's alpha coefficients were 0.81 (adolescent form) and 0.92 (adult form). The scale-level content validity indexes were acceptable (0.88 and 0.89 for the adolescent and adult forms, respectively). The total domain and overall HRQoL scores were calculated. Results: Sixty-two survivors completed the adolescent form and 30 completed the adult form. The median age was 17.5 years (range 13-34 years), and the median time from diagnosis was 12 years (male:female ratio 1:1.2). Risk factors for poor physical functioning included age at study visit (p = 0.015), solid tumor diagnosis (p = 0.012), radiotherapy (p = 0.021), and surgery (p = 0.006). Six or more late effects impacted most domains negatively; severe late effects (p = 0.020) decreased physical functioning. Lower socioeconomic status was associated with poorer physical (p = 0.006) and cognitive (p = 0.047) functioning. The adult form cohort had poorer psychological (p = 0.014) and social functioning (p = 0.005) and body image (p = 0.016) than the adolescent form cohort. Conclusion: Older age, radiotherapy, surgery, solid tumor diagnosis, and the number and severity of late effects negatively influenced HRQoL in AYA-aged CCSs. A long-term follow-up (LTFU) risk stratification system should include HRQoL status to assist with holistic LTFU care.

Non-primary solid malignancies of breast in needle core biopsy: a clinicopathological analysis of 23 cases

Objective: To investigate the accurate diagnosis and differential diagnosis of non-primary solid malignant tumors in breast needle core biopsy. Methods: Twenty-three cases of breast, axilla or neck lymph nodes pathologically diagnosed as non-primary solid malignant tumors were collected at the First Affiliated Hospital of Nanjing Medical University, Nanjing, China from January 2013 to March 2023. The differential diagnoses and diagnostic features were analyzed, based on combining clinical data, histology, and expression characteristics of biomarkers. Results: All patients were female, with age ranging from 29 to 75 years (average 56 years). The average time from the diagnosis of primary tumor to the current diagnosis was 21 months (0 to 204 months).The primary sites included the ovary (9 cases), the lung (5 cases), the gastrointestinal tract (4 cases), the pancreas, intrahepatic bile duct, thyroid gland, nasal cavity and forearm skin (1 case each). No carcinoma in situ was found in any of the cases. The morphological differences were significant among the tumors, but similar to the primary tumors. The tumors of neuroendocrine and female reproductive tract had great morphological and immunophenotypic overlaps with breast cancer. Metastatic lung cancer cells showed obvious atypia and tumor giant cells. The morphology and immunophenotype of metastatic serous carcinoma of female reproductive system might resemble invasive micropapillary carcinoma of the breast. Metastatic adenocarcinoma of the gastrointestinal tract often had features of mucous secretion. Metastatic neuroendocrine tumors were bland in appearance and morphologically similar to solid papillary carcinoma of breast, but negative for ER. TRPS1 was mostly negative (18/23) and variably positive in ovarian (4/9) and intrahepatic bile duct (1/1) tumors. Conclusions: The diagnosis of breast needle core biopsy specimen should be combined with clinical history, imaging study, and careful examination of histological features, such as presence of in situ component, morphological similarity between the primary and metastatic tumors, and using appropriate markers to differentiate the primary from metastatic tumors.

[99mTc]Tc-labeled HYNIC conjugated chlorambucil as a tumor targeting Agent: Synthesis, characterization and ex-vivo evaluation

Chlorambucil is an alkylating drug that finds application towards chemotherapy of different types of cancers. In order to explore the possibility of utilization of this drug as an imaging agent for early diagnosis of solid tumors, attempt was made to synthesize a 99mTc complex of chlorambucil and evaluate its potential in tumor bearing small animal model. HYNIC-chlorambucil was synthesized by conjugation of HYNIC with chlorambucil via an ethylenediamine linker. All the intermediates and final product were purified and characterized by standard spectroscopic techniques viz. FT-IR, 1H/13C-NMR as well as by mass spectrometry. HYNIC-chlorambucil conjugate was radiolabeled with [99mTc]Tc and found to be formed with > 95 % radiochemical purity via RP-HPLC studies. The partition coefficient (Log10Po/w) of the synthesized complex was found to be −0.78 ± 0.25 which indicated the moderate hydrophilic nature for the complex. Biological behaviour of [99mTc]Tc-HYNIC-chlorambucil, studied in fibrosarcoma bearing Swiss mice, revealed a tumor uptake of about 4.16 ± 1.52 %IA/g at 30 min post-administration, which declined to 1.91 ± 0.13 % IA/g and 1.42 ± 0.14 %IA/g at 1 h and 2 h post-administration, respectively. A comparison of different [99mTc]Tc-chlorambucil derivatives (reported in the contemporary literature) formulated using different methodologies revealed that tumor uptake and pharmacokinetics exhibited by these agents strongly depend on the lipophilicity/hydrophilicity of such agents, which in turn is dependent on the bifunctional chelators used for formulating the radiolabeled chlorambucils.

Children with non-central nervous system tumors treated with platinum-based chemotherapy are at risk for hearing loss and cognitive impairments.

Childhood cancer survivors (CCS) with chemotherapy induced sensorineural hearing loss (SNHL) are at risk for neurocognitive impairments. The purpose of this study was to determine the relationship between SNHL and cognitive function among CCS. Inclusion: non-CNS solid tumor diagnosis; history of platinum chemotherapy (cisplatin and/or carboplatin); 8-17 years of age; off anti-cancer treatment for ≥6 months; and English speaking. Exclusion: history of intrathecal chemotherapy, cranial radiation, or baseline neurocognitive disorder. Participants completed the NIH Toolbox Cognition Battery at enrollment. T-tests were used to compare participants with normal hearing to those with hearing loss and the total sample with established Toolbox normative data (mean: 50; SD: 10). Fifty-seven individuals enrolled; 52 completed full cognitive testing. Participants were on average 12.2 years of age and 7.0 years since treatment completion. Twenty-one participants (40%) received cisplatin, 27 (52%) carboplatin, and 4 (8%) received both. Fifteen participants (29%) demonstrated SNHL based on the better ear. CCS, regardless of the presence or absence of SNHL, demonstrated significantly lower mean cognitive skills compared to the normative sample in attention, executive function, language- vocabulary and oral reading, processing speed, and fluid, crystallized and total composite scores (all p < 0.01). Participants with SNHL had significantly lower crystallized composite (vocabulary, oral reading) than those with normal hearing (41.9 vs. 47.2, p < 0.05, Cohen's d = 0.62). CCS at risk for platinum induced hearing loss but without cranial radiation or intrathecal chemotherapy exposure demonstrate impaired cognitive skills and those with SNHL demonstrate lower crystallized composite scores.

Peptide-Functionalized Inorganic Oxide Nanomaterials for Solid Cancer Imaging and Therapy.

The diagnosis and treatment of solid tumors have undergone significant advancements marked by a trend toward increased specificity and integration of imaging and therapeutic functions. The multifaceted nature of inorganic oxide nanomaterials (IONs), which boast optical, magnetic, ultrasonic, and biochemical modulatory properties, makes them ideal building blocks for developing multifunctional nanoplatforms. A promising class of materials that have emerged in this context are peptide-functionalized inorganic oxide nanomaterials (PFIONs), which have demonstrated excellent performance in multifunctional imaging and therapy, making them potential candidates for advancing solid tumor diagnosis and treatment. Owing to the functionalities of peptides in tumor targeting, penetration, responsiveness, and therapy, well-designed PFIONs can specifically accumulate and release therapeutic or imaging agents at the solid tumor sites, enabling precise imaging and effective treatment. This review provides an overview of the recent advances in the use of PFIONs for the imaging and treatment of solid tumors, highlighting the superiority of imaging and therapeutic integration as well as synergistic treatment. Moreover, the review discusses the challenges and prospects of PFIONs in depth, aiming to promote the intersection of the interdisciplinary to facilitate their clinical translation and the development of personalized diagnostic and therapeutic systems by optimizing the material systems.

Evaluating the Patterns of FAPI Uptake in the Shoulder Joint: a Preliminary Study Comparing with FDG Uptake in Oncological Studies

BackgroundFibroblast activation protein inhibitor (FAPI) targeting PET has been introduced as a novel molecular imaging modality for visualizing cancer-associated fibroblasts. There have also been reports suggesting incidental findings of localized accumulation in the shoulder joints. However, further characterization in a larger patient cohort is still lacking.Methods77 consecutive patients (28 females; mean age, 63.1 ± 11.6) who underwent Ga-68 FAPI-04 PET/CT for diagnosis of solid tumors were included. The incidence and localization of tracer uptake in shoulder joints were investigated and compared with available F-18 FDG scans serving as reference.ResultsGa-68 FAPI-04 uptake was evaluated in 77 patients (154 shoulder joints), of whom 54 subjects (108 shoulder joints) also had available F-18 FDG scans for head-to-head comparison. On FAPI-targeted imaging, 67/154 shoulders (43.5%) demonstrated increased radiotracer accumulation in target lesions, which were distributed as follows: acromioclavicular (AC) joints in 25/67 (37.3%), followed by glenohumeral and subacromial (GH + SA) joints in 23/67 (34.3%), or both (AC and GH + SA joints) in the remaining 19/67 (28.4%). Ga-68 FAPI-04 correlated with quantified F-18 FDG uptake (r = 0.69, p < 0.0001). Relative to the latter radiotracer, however, in-vivo FAP expression in the shoulders was significantly increased (Ga-68 FAPI-04, 4.7 ± 3.2 vs F-18 FDG, 3.6 ± 1.3, p < 0.001).ConclusionOur study revealed focal accumulation of Ga-68 FAPI-04 in the shoulders, particularly in the AC joints, with higher uptake compared to the inflammatory-directed PET radiotracer F-18 FDG in oncological studies. As a result, further trials are warranted to investigate the potential of FAPI-directed molecular imaging in identifying chronic remodeling in shoulder joints. This could have implications for initiating anti-FAP targeted photodynamic therapy based on PET signal strength.

EUS-guided tissue acquisition in patients with solid pseudopapillary neoplasms of the pancreas

ABSTRACT Objectives Endoscopic ultrasound-guided tissue acquisition (EUS-TA) has been the most common method used for the preoperative cytopathological diagnosis of solid tumors of the pancreas. There are only a few reported cases about the role of endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) in the pre-operative diagnosis of solid pseudopapillary neoplasms (SPN). This study aimed to evaluate the diagnostic yield of EUS-TA,including endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) andEUS-FNB, in patients with SPN. Methods We performed a retrospective analysis of patients with EUS-TA for SPN diagnosis in 2 referral centers. The primary outcome was the diagnostic yield of EUS-TA compared to the surgical specimen. Results Seventy-four patients with SPN of the pancreas were identified. Eighteen had a EUS-TA (10 EUS-FNB and 8 EUS-FNA). The median age of the patients was 31 years (IQR 21–38), and all patients were women. The most common presenting symptom was abdominal pain. Most of the tumors were in the head of the pancreas (9/18; 50%). The median tumor size by EUS was 4.5 cm (min-max 2–15 cm). The most common appearance on EUS was a solid lesion (n = 8/18, 44.4%). A definitive presurgical cytopathological diagnosis was obtained in 16/18 patients (88.8%) with EUS-TA. The sensitivity and positive predictive value of the EUS-TA were 94% each. One patient in the EUS-FNB group developed mild acute pancreatitis. Conclusion The diagnostic yield of the EUS-TA in SPN is high. In most cases, the diagnosis was obtained with the first procedure. No differences in the diagnostic yield or AEs between EUS-FNA vs. EUS-FNB needles were seen.

Diagnosis and treatment of solid pseudopapillary tumor of the pancreas: A single center's experience.

The present study reviews the records of patients with solid pseudopapillary pancreas neoplasm (SPT). A total of 13 patients diagnosed with SPT were included in the study. The criteria for SPT in the pathology specimens were the presence of cells with an oval round orthochromatic nucleus, with a thin chromatin structure and no nucleolus distinction, lined around a fibrovascular papilla in cystic areas. The study included 11 female and two male patients, with a mean age of 33.07 (range: 16-73) years. All operated patients underwent open surgery, with five undergoing a subtotal pancreatectomy and splenectomy; one a distal pancreatectomy and splenectomy; four a spleen-preserving distal pancreatectomy; and one a pancreaticoduodenectomy. None of the operated patients developed recurrence during the long-term follow-up. The mean follow-up time of operable patients was 69.18 (range: 22-97) months, and none had metastasis at follow-up. The mean follow-up time for the malignant SPT patients was 2.75 (1.5-4) months. SPTs are rare pancreatic tumors encountered more frequently today due to advances in imaging methods and have a low potential of recurrence and a good prognosis.

Oxygen and pH responsive theragnostic liposomes for early-stage diagnosis and photothermal therapy of solid tumours.

The development of cancer treatment is of great importance, especially in the early stage. In this work, we synthesized a pH-sensitive amphiphilic ruthenium complex containing two alkyl chains and two PEG chains, which was utilized as an oxygen sensitive fluorescent probe for co-assembly with lipids to harvest a liposomal delivery system (RuPC) for the encapsulation of a photothermal agent indocyanine green (ICG). The resultant ICG encapsulated liposome (RuPC@ICG) enabled the delivery of ICG into cells via a membrane fusion pathway, by which the ruthenium complex was localized in the cell membrane for better detection of the extracellular oxygen concentration. Such characteristics allowed ratiometric imaging to distinguish the tumour location from normal tissues just 3 days after cancer cells were implanted, by monitoring the hypoxia condition and tracing the metabolism. Moreover, the pH sensitivity of the liposomes favoured cell uptake, and improved the anti-tumour efficiency of the formulation in vivo under NIR irradiation. Assuming liposomal systems have fewer safety issues, our work not only provides a facile method for the construction of a theragnostic system by combining phototherapy with photoluminescence imaging, but hopefully paves the way for clinical translation from bench to bedside.

Biopsias líquidas en cáncer: ¿estamos preparados para remplazar el tejido tumoral?

The use of liquid biopsy (LB) has become highly relevant in the clinical field, and the acquisition of circulating free DNA (cfDNA) has become consolidated as an emerging biomarker and a tool for the research, diagnosis, and prognosis of solid tumors (1). Different studies have confirmed that this type of DNA contains information on specific tumor-related alterations, such as mutations, methylations, and copy number variants (CNVs) (2). The most striking advantage of LB is its ability to isolate ctDNA through a minimally invasive technique (1,3).

Supportive care and healthcare service utilisation in older adults with a new cancer diagnosis: a population-based review

ObjectivesOlder adults have unique needs and may benefit from additional supportive services through their cancer journey. It can be challenging for older adults to navigate the siloed systems within cancer...

CT target scanning in the diagnosis of solid pseudopapillary tumor of the pancreas

ObjectiveTo discuss the value of computed tomography (CT) iterative reconstruction technique combined with target scanning in the diagnosis of solid pseudopapillary tumor of the pancreas (SPTP).MethodsThe clinical information and CT examination data of 27 patients with SPTP were retrospectively analyzed, and the general condition and CT performance of the patients were observed. The CT image reconstruction algorithm of all patients used iterative reconstruction technique combined with the application of target scanning technique.ResultsA total of 27 patients were included in this study, including 6 males and 21 females, aged 14–72 years with a mean age of 39.6 ± 13.6 years. SPTP was more common in young and middle-aged females, with a low level of tumor markers, dominated by cystic-solid tumors. The combination of CT iterative reconstruction technology and targeted scanning revealed the following: the capsule of SPTP was clear and complete, where calcifications were visible, solid components were progressively enhanced, and rare pancreatic and bile duct dilation was seen. Tumors were cystic-solid in 18 of 27 patients with SPTP, of which the solid components showed isodensity or slightly low-density, with calcifications. The solid components and cyst walls were mildly enhanced during the arterial phase, and were progressively enhanced during the parenchymal phase, portal vein phase, and delayed phase, with their enhancement degree lower than that of normal pancreatic parenchyma, and pancreatic and bile duct dilation was rare. There were no statistical differences in tumor location, morphology, growth pattern, integrity of capsule, cystic or solid, calcifications, and enhancement features between the male group and the female group (P > 0.05).ConclusionThe iterative reconstruction combined with target scanning clearly displayed the CT features of tumors, helping the diagnosis and clinical treatment of the disease.

OP22 Benchmarking Of Population-Based Childhood Cancer Survival By Toronto Stage: Know The Differences To Propose Effective Interventions

IntroductionPediatric cancers are rare tumors, heterogeneous in location and biologically very different from adult cancers. Documented survival variation across European countries and Italian regions shows that there is still room for further improvement by reducing inequalities. We aim to understand why there are differences in survival. The BENCHISTA-ITA project (National Benchmarking of Childhood Cancer Survival by Stage at diagnosis), that is the Italian twin project of the International BENCHISTA, collects stage at diagnosis of solid pediatric tumors, according to the Toronto Guidelines. We will compare how far the cancer has spread at diagnosis and test if differences in tumor stage explain any survival differences between Italian regions.MethodsThe project study involved the stage distribution and the survival of 9 pediatric solid tumors diagnosed between 2013 and 2017 in Italy. All patients therefore had at least 3 years of follow-up in 2021 for life-stage definition. The study involves the identification of all new diagnoses of cancer, evaluation of the clinical documentation of cases eligible for research, and international classification and coding. Analyses of stage distribution and survival rates for each tumor type will be described.ResultsData from 35 population-based cancer registries from 18 out of 20 Italian regions were collected covering about 84 percent of the Italian child population. In particular, data on: imaging/examination performed before any treatment; source used for staging; primary treatment defined as given within one year from diagnosis; relapse/ recurrence/ progression; follow up and status of life. The study tested the applicability of the Toronto Guidelines as a tool to obtain population-level comparable stage information for childhood cancers. There were 1,343 cases collected (242 Neuroblastoma, 124 Wilms Tumour, 145 Medulloblastoma, 148 Osteosarcoma, 135 Ewing sarcoma, 115 Rhabdomyososarcoma, 54 Ependymoma, 47 Retinoblastoma, 333 Astrocytoma). Toronto stage could be assigned in more than 90 percent in the majority of tumors. Tumors in which it was more difficult to assign the stage using the Toronto staging guidelines were ependymoma, astrocytoma, and retinoblastoma. It was easier to retrieve data for patients in the 0-14 years of age range than adolescents (14-18 years). Differences in stage distribution and survival differences between regional grouping were presented.ConclusionsThe Italian BENCHISTA project, improving the connection between pediatric cancer registries, aims to improve care of children with cancer across the nation, reducing possible disparities.The wide adoption of the Toronto Guidelines will facilitate international comparative incidence studies, strengthen the interpretation of survival data, and contribute to more appropriate solutions to improve childhood cancer outcomes.

Therapy Related Multiple Myeloma: A Distinct Entity

Background The development of therapy-related multiple myeloma (t-MM) is a poorly described entity. Multiple myeloma (MM) is the second most common hematologic malignancy. Despite significant strides in MM treatment over recent decades, identifying modifiable risk factors, optimizing screening methodologies, and identifying potential treatment strategies or targets to address t-MM remains of utmost importance, as this disease continues to pose a significant therapeutic challenge and remains incurable. This retrospective review seeks to explore the incidence and characteristics of t-MM at a medium-sized, academic center. Methods We performed a single institution retrospective chart review of patients diagnosed with multiple myeloma between 2008-2023 and evaluated for prior diagnosis of solid malignancy, excluding all skin cancers, lymphomas or myeloproliferative neoplasm (MPN). We collected data for the following: prior treatment for solid malignancy, lymphoma or MPN, lapsed time between prior therapy and development of MM, cytogenetics, prominent subtype present, renal failure and hypercalcemia if present at time of diagnosis, management of t-MM including transplant data, disease progression including relapse status, and survival data. Results In our study, we identified a subgroup of 17 individuals who had a previous history of solid malignancy, 1 patient with unknown prior solid tumor, 1 patient with history of Hodgkin's lymphoma, and 1 additional patient with history of MPN who received chemotherapy and/or radiation therapy, with 3 patients having MGUS prior to development of MM. Notably, among this population, 70% were male. All patients developed MM following the treatment for a solid malignancy, lymphoma or MPN. The average amount of time from diagnosis of solid tumor, lymphoma or MPN to development of MM was 9.53 years (1-25 years). 50% of the individuals were White Americans, while the remaining 50% were African Americans. A significant majority (85%) of the population had a single primary solid tumor. Among the primary solid tumors, 45% were prostate cancer, 15% were breast cancer, and 10% were renal cell carcinoma (Figure 1). 5 patients received chemotherapy alone without documented prior radiation exposure while 13 had prior radiation exposure for prior solid malignancy. At time of diagnosis, 45% of patients had renal failure with 10% of patients having both renal failure and hypercalcemia. Within the t-MM subtypes, we discovered that 50% had IgA type, with 70% of these individuals exhibiting the IgA Kappa subtype. 45% of the individuals who developed t-MM had the IgG type, with 78% of them with IgG Kappa subtype. 15 (75%) of the patients received transplant and only 2 patients had confirmed relapse with 2 patients unknown and 2 additional patients who passed away prior to starting maintenance therapy following transplant. 4 patients are very early in their disease process and as of yet have not undergo transplant. 55% of our patients are presumed living. The OS for patients with t-MM was 1190 days compared to the average OS of 2326 days in our institutional MM database without t-MM. Conclusion Our analysis focused on patients diagnosed with MM who had a prior history of solid primary tumors, lymphoma or MPN treated with chemotherapy and/or radiotherapy in hopes of providing valuable insights into the characteristics and outcomes of individuals who developed MM following treatment for solid tumors, lymphoma or MPN. Our findings highlighted specific risk factors associated with t-MM in this population. Being male and having a history of prostate cancer was associated with higher incidence of development of t-MM. This is likely related to the radiation therapy associated with prostate cancer, as radiation exposure has been a known risk factor for the development of MM. We observed that the predominant subtype of MM among these individuals was IgA kappa, which diverges from the prevalent subtype, IgG kappa, observed in the general population. IgA is known to typically have more cytogenetic abnormalities and overall poorer prognosis, likely contributing to the difference in OS compared to patients with t-MM and MM not associated with prior malignancy. These insights shed light on the unique characteristics and potential influences of treatment-related MM in patients with prior malignancies or MPN.

Diagnostic impact of RNA-based next-generation sequencing fusion panel for solid tumors: A single-institution experience.

Gene rearrangements frequently act as oncogenic driver mutations and determine the onset and progression of cancer. RNA-based next-generation sequencing (NGS) is being used with increasing frequency for solid tumors. The purpose of our study is to investigate the feasibility and utility of an RNA-based NGS fusion panel for solid tumors. We conducted a retrospective, single-institution review of fusion panels requested between May 2022 and March 2023. Demographic, clinical, pathologic, and molecular findings of the patients were reviewed. The utility of the RNA-based NGS fusion panel for the pathologic diagnosis of solid tumors was assessed. Our study included 345 cases, and a fusion event was identified in 24.3% (78/321) of cases. Among the 110 cases submitted for diagnostic purposes, a fusion event was detected in 42.7% (47/110) of cases. The results led to refinement or clarification of the initial diagnosis in 31.9% (15/47) of cases and agreement or support for the initial diagnosis in 59.6% (28/47) of cases. Furthermore, our study indicated that the overall cellularity (tumor and normal tissue) of the tested specimen influences the success of the testing process. In summary, this study demonstrated the feasibility and utility of an RNA-based NGS fusion panel for a wide variety of solid tumors in the appropriate clinicopathologic context. These findings warrant further validation in larger studies involving multiple institutional patient cohorts.

Primary ovarian insufficiency in cancer survivors: Keys to optimal management

IntroductionPrimary ovarian insufficiency (POI) carries significant morbidity, causing infertility, sexual disfunction, decreased bone density, cardiovascular risk, emotional distress and early mortality. ObjectiveTo know the incidence and current management of POI in childhood/adolescent solid tumour survivors. Material and methodsWe conducted a multicentre observational study. It included female patients aged 12–18 years with a diagnosis of solid tumour and meeting clinical or biochemical criteria for POI. The risk was estimated based on the criteria of the Pediatric Initiative Network of the Oncofertility Consortium. ResultsWe found an incidence of 1.5 (30 cases of POI): The median age at the time of the event was 14 years (standard deviation, 2.09). The solid tumours associated most frequently with POI were Ewing sarcoma and brain and germ cell tumours. Eighty-three percent of patients did not undergo fertility preservation. Sixty-three percent reported not having undergone menarche at the time of ovarian failure. Ninety-seven percent were at high risk of gonadal toxicity, yet 47% were not monitored before the diagnosis. The median time elapsed to the occurrence of the event was 43.5 months after diagnosis and 29.5 months after completing treatment. The Kaplan-Meier curves showed that approximately 30% of POI cases developed within 2 years of diagnosis and that women at Tanner stage 1 developed insufficiency later than women at Tanner stage 5. ConclusionsThere is room for improvement in the follow-up of women at risk of POI in Spain. The tools currently available facilitate risk assessment at the time of treatment planning and allow the implementation of monitoring, education, early diagnosis, fertility preservation, and replacement therapy as needed. All of this would achieve significant improvement in health outcomes.