Search Results (362)

The management of oligometastatic disease has undergone a significant paradigm shift over the past two decades. Once considered uniformly incurable, selected patients with metastatic disease can now achieve prolonged progression-free survival, durable disease control, and, in carefully selected cases, long-term remission or cure through metastasis-directed therapies. Advances in stereotactic ablative radiotherapy (SABR), surgery, systemic therapies, and the emerging concept of Curative Oligometastatic Radiotherapy (CORT) have challenged the traditional distinction between curative and palliative treatment. Concurrent developments in imaging, including PET/CT, prostate-specific membrane antigen (PSMA) PET, whole-body MRI, and MR-guided adaptive radiotherapy (MR-linac), together with evolving biomarker research, are improving disease characterisation, refining patient selection, and treatment personalisation. As survival improves, an increasing number of patients are living with durably controlled metastatic cancer and experience long-term physical, psychological, cognitive, functional, and financial consequences of treatment. Despite these challenges, evidence-based survivorship pathways for patients with oligometastatic disease remain poorly defined. Supportive oncology is becoming an essential component of modern radiation oncology rather than an adjunct to cancer treatment. This emerging discipline focuses on optimising symptom control, minimising toxicity, and delivering structured survivorship care. Rather than being limited to end-of-life care, supportive oncology is embedded throughout the patient journey; from diagnosis and treatment selection to prehabilitation, rehabilitation, patient-reported outcome (PRO) monitoring, surveillance for late effects, multidisciplinary follow-up, and long-term survivorship. This review discusses how advances in precision radiotherapy, molecular imaging, biomarkers, and emerging treatment technologies are reshaping the management of oligometastatic disease while simultaneously creating a growing population of long-term survivors with increasingly complex supportive care needs. It highlights the expanding role of supportive oncology in the care of patients with oligometastatic disease, encompassing multidisciplinary symptom management and argues that improvements in disease control must now be matched by the development of evidence-based multidisciplinary survivorship pathways that integrate supportive oncology to optimise quality of life (QoL), functional independence, and patient-centred outcomes. Finally, this review highlights current evidence gaps and proposes future research priorities for developing evidence-based survivorship models for this rapidly expanding patient population. Full article

Background/Objectives: To determine treatment-free probability after persistent low-level human chorionic gonadotropin (hCG) elevation following complete remission from gestational trophoblastic neoplasia (GTN) and examine its association with the early hCG course. Methods: This single-center retrospective study included patients treated in 2015–2022 for gestational choriocarcinoma or invasive mole who developed ≥3 post-remission hCG results >5 and ≤1000 U/L over ≥14 days. The primary endpoint was retreatment for GTN recurrence. Kaplan–Meier analysis estimated treatment-free probability from the first low-level hCG elevation. Exploratory landmark analyses at 60, 90, and 180 days stratified patients still under observation by pre-landmark peak hCG (≤20 versus >20 U/L). Results: Forty-six patients contributed 595 hCG measurements. Thirty-five developed recurrence requiring retreatment; 11 remained recurrence-free. All patients whose first low-level hCG exceeded 20 U/L (n = 11) developed recurrence. Treatment-free probability was 30.4% at 1 year and 24.2% at 2 years. At the 60-, 90-, and 180-day landmarks, 365-day treatment-free probability was higher with pre-landmark peak hCG ≤ 20 U/L than >20 U/L: 68.4% versus 9.1%, 70.6% versus 22.2%, and 92.3% versus 14.3%, respectively. All 35 retreated patients achieved hCG ≤ 5 U/L after treatment. Conclusions: Most patients with persistent low-level hCG after remission from GTN developed recurrence. For patients still under observation at 60, 90, or 180 days, a peak hCG of 20 U/L or lower before the landmark was associated with higher treatment-free probability over the following year. Continued surveillance after clinical and imaging assessment is reasonable in this subgroup. Full article

Background: Dual immune checkpoint inhibitor therapy with nivolumab plus relatlimab has substantial clinical activity against metastatic melanoma. The incidence and timing of endocrine immune-related adverse events with this treatment remain poorly characterized. Methods: We conducted a retrospective record review of 52 sequential patients who received nivolumab plus relatlimab as initial therapy for metastatic cutaneous melanoma. All patients underwent sequential endocrine screening (TSH, FT4, ACTH, cortisol) prior to each monthly treatment cycle. The incidence and onset of hypothyroidism and hypopituitarism were evaluated, as was cancer treatment outcome. Results: Biochemical evidence for endocrinopathy was identified in 25% of patients. This included a 13.5% incidence of hypothyroidism (median onset 79.0 ± 63.9 days) and 11.5% incidence of hypopituitarism (median onset 243.5 ± 75.6 days). Due to screening and early replacement therapy, there were no related hospitalizations. Patients who developed endocrinopathy showed a trend toward improved progression-free and overall survival. An exploratory analysis suggested that the incidence of endocrinopathy was significantly lower in patients treated with nivolumab plus relatlimab than in those treated with ipilimumab plus nivolumab. Conclusions: During treatment with nivolumab plus relatlimab, endocrinopathy developed in approximately 25% of metastatic melanoma patients, emphasizing a need for screening testing. In an exploratory analysis, endocrinopathy appeared less frequent than in ipilimumab-plus-nivolumab-treated patients. Recovery from endocrinopathy appeared uncommon. Development of delayed endocrinopathy following elective treatment discontinuation for patients in remission was rare (3.8%). Patients who developed endocrinopathy showed a trend toward improved clinical outcome. Full article

Background and Objectives: Head and neck cancer in patients aged 40 years or younger represents a rare and heterogeneous entity with conflicting data regarding prognosis and risk factors. This study aimed to evaluate oncological outcomes and independent prognostic factors in young patients treated with radio(chemo)therapy. Materials and Methods: This retrospective multi-center analysis included patients aged ≤ 40 years with histologically confirmed HNC who received definitive or adjuvant radio(chemo)therapy between 2002 and 2023 at the University Hospital Regensburg and affiliated partner hospitals. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan–Meier method. Independent prognostic factors were identified by Cox proportional hazard regression with backward stepwise elimination. Results: A total of 88 patients were included. The median age at diagnosis was 38.2 years (IQR 35.8–39.8). Median OS was 91.0 months in the adjuvant and 23.7 months in the definitive treatment group. In multivariate analysis, four independent predictors of OS were identified: nicotine abuse (HR 2.887; p = 0.004), pre-existing comorbidities (HR 2.871; p = 0.005), absence of complete remission 12 weeks after radiotherapy (HR 25.676; p < 0.001), and locoregional recurrence or distant metastases (HR 8.183; p < 0.001). Failure to achieve complete remission was the sole independent predictor of PFS (HR 4.479; p < 0.001). Conclusions: In young HNC patients, early treatment response and disease recurrence are the strongest determinants of survival, alongside modifiable lifestyle factors and comorbidity burden. These findings support the need for intensified response monitoring and tailored follow-up strategies in this patient population. Full article

The treatment of chronic lymphocytic leukemia (CLL) has shifted from chemoimmunotherapy to targeted therapy, resulting in improved outcomes and patient survival. The aim of this study was to evaluate the efficacy and safety of venetoclax-based regimens in patients with relapsed/refractory CLL, as well as their effectiveness in patients previously treated with ibrutinib. We retrospectively analyzed 98 patients with CLL who received venetoclax in the second or later lines of therapy in Slovakia between 2018 and 2024. The median age was 68 years, and treatment was administered either as monotherapy or in combination with rituximab. Response to treatment was assessed according to the iwCLL 2018 criteria and clinical practice. Patients who achieved complete hematologic and clinical remission but did not undergo confirmatory bone marrow examination were classified as having unconfirmed complete remission (uCR). An overall response was achieved in the majority of patients (in 99%), with 2% achieving complete remission, 65% incomplete complete remission and 32% partial remission. At a median follow-up of 34 months, median overall survival was not reached (mean 52.5 months), and median progression-free survival was 45 months. Survival outcomes were evaluated using Kaplan–Meier analysis. Patients previously treated with ibrutinib had significantly worse outcomes (p = 0.022). Adverse events were predominantly hematological (64%), with 19% being grade 3–4. In line with the conclusions of clinical trials and retrospective analysis from real-life practice, we can say that venetoclax-based treatment regimens are highly effective in patients with CLL in higher lines of treatment, with acceptable and well-manageable toxicity. Full article

Background/Objectives: Azacitidine (AZA) is the standard of care for patients with higher-risk Myelodysplastic Syndromes (MDS). There is limited real-life data, however, characterizing its efficacy and safety profile in elderly patients. Methods: We conducted a single-center retrospective cohort chart review to compare front-line AZA therapy in patients ≥75 years (elderly) vs. <75 years (younger) with higher-risk MDS treated at our cancer center. The primary endpoint was overall survival and main secondary endpoints included response, as per the 2006 International Working Group consensus criteria, leukemia-free survival, transfusion independence, and safety outcomes. Results: In total, 55 patients were elderly (median age: 79.9 years), including 27 patients >80 years, and 41 were younger (median age: 69.4 years). Baseline demographic variables were similar between both groups. The majority of elderly patients (98%) received the full dose of AZA (75 mg/m²), compared with 90% of younger patients. The median number of AZA cycles was 8 (range: 2–69) in elderly and 7.75 (range: 1–96) in younger patients. Treatment delays occurred in 36.4% of elderly and 29.3% of younger patients, most commonly due to infection complications in both groups (p = 0.076). Disease control rates (complete remission + partial remission + stable disease) were 92.9% in the younger subgroup and 96.4% in the elderly subgroup (p = 0.154). Relapse occurred in 48.8% of younger patients and 40.0% of elderly patients. Median overall survival (OS) was 17.3 months for the younger subgroup, 15.7 months for the elderly subgroup (p = 0.771), and 11.9 months among patients >80 years (p = 0.381). Mortality rates and causes of death were similar between both subgroups. Most common causes of death included disease progression, sepsis, febrile neutropenia, and pneumonia. Conclusions: AZA monotherapy resulted in a high response rate and was well-tolerated in elderly patients with higher-risk MDS. These findings remain consistent in the real-world setting despite potential confounding factors that may contribute to inferior outcomes. Full article

Background: Treatment-resistant schizophrenia (TRS) affects approximately 20–30% of patients and is associated with significant disability. EEG abnormalities, particularly background slowing and disorganized alpha activity, have been reported in TRS, but the role of alpha rhythm instability—here termed alpha dysrhythmia—remains poorly understood. Objective: To compare the individual alpha frequency (IAF) between patients with TRS and those in clinical remission, to examine associations between alpha dysrhythmia and specific symptom domains (especially disorganization), and to investigate its relationship with EEG background changes. Methods: Eighty-nine patients with schizophrenia were included. Alpha dysrhythmia was defined as intraindividual variability of dominant alpha frequency exceeding 1 Hz across consecutive EEG epochs. Quantitative spectral analysis was performed using FFT on artifact-free 4–9 s epochs. Clinical assessment included PANSS (positive, negative, and disorganized subscales), the Dissociation scale, BPRS, Hamilton D/A, and the OCD scale. Group comparisons used the Mann–Whitney U test; correlations used Pearson and Spearman coefficients; and stepwise regression identified independent predictors. Results: Alpha dysrhythmia was present in 46.1% of patients. Significant negative correlations were found between dysrhythmia and therapeutic response. Significant positive correlations were found with PANSS disorganized symptoms and the Dissociation scale. The Mann–Whitney U test showed that the dysrhythmia group had higher mean ranks for EEG background factor (EEG BA), the Dissociation scale, and PANSS disorganized symptoms. Stepwise regression identified EEG BA and the Dissociation scale as independent predictors. Conclusions: Alpha dysrhythmia is frequent in TRS patients and is specifically associated with poorer therapeutic response, disorganized symptoms, and dissociation. EEG BA (reflecting background changes) may serve as a neurophysiological biomarker for identifying patients at risk for treatment resistance. Full article

Pediatric acute myeloid leukemia (AML) is biologically heterogeneous, and genomic profiling increasingly informs risk stratification and treatment. We evaluated the relationship between induction response, genomic risk, transplant allocation, and survival in pediatric AML. We retrospectively analyzed 38 pediatric patients with newly diagnosed AML, treated between 2020 and 2025. Clinical, cytogenetic, molecular, treatment, and outcome data were collected. Genomic alterations were assessed using cytogenetics, fluorescence in situ hybridization (FISH), molecular testing, and next-generation sequencing (NGS). Survival was estimated by Kaplan–Meier analysis, and prognostic factors for event-free survival (EFS) were assessed using univariable Cox regression. This study is exploratory given the limited sample size and should be interpreted accordingly. Complete remission (CR) after the first course of induction was achieved in 25/38 patients (65.8%), partial remission (PR) in 3/38 (7.9%), and refractory disease in 10/38 (26.3%). Twenty-four patients underwent allogeneic hematopoietic stem cell transplantation; 17/24 (70.8%) were alive at last follow-up, with a 2-year overall survival rate of 72.9%. Both induction response and genomic risk stratification showed suggestive associations with outcome; descriptively, induction response showed the strongest prognostic discrimination, with achievement of CR associated with markedly improved survival. High cytogenetic risk and FLT3-ITD were significantly associated with inferior EFS. Post-induction measurable residual disease (MRD) positivity was detected in 16 of 38 patients (42.1%) and was associated with suboptimal induction response; MRD negativity did not uniformly preclude adverse outcomes, particularly in the high-risk genomic subgroup. Genomic profiling refined biological risk and post-remission treatment allocation. Integrated assessment of genomic risk, induction response, and MRD status may improve therapeutic stratification in pediatric AML. Full article

Background: BCMA-targeted Chimeric Antigen Receptor (CAR) T-cell therapy has revolutionized the treatment of Relapsed/Refractory Multiple Myeloma (RRMM). However, the disease is not curable and progression after CAR T-cell treatment remains a challenge. Clonal hematopoiesis, specifically mutations in the DNA damage response gene PPM1D, has been linked to therapy resistance and inferior survival in lymphoma patients undergoing cellular therapy. The impact of PPM1D mutations on MM patient outcome after CAR T-cell therapy remains undefined. Methods: We conducted a retrospective single-center study of 83 patients with RRMM patients treated with idecabtagene vicleucel or ciltacabtagene autoleucel between 2022 and 2025. Next-generation sequencing was performed on peripheral blood mononuclear cells collected prior to CAR T-cell infusion to identify PPM1D exon 6 mutations (variant allele frequency > 0.01). We analyzed associations between mutational status, clinical characteristics, toxicity, and survival. Results: PPM1D mutations were detected in 14.5% (12/83) of patients. PPM1D-mutated patients had fewer prior autologous stem cell transplantation compared to wild-type patients (50% vs. 82%, p = 0.02) and presented more advanced disease burden and adverse prognostic features (R-ISS stage III 58% vs. 20%, p = 0.05). Notably, PPM1D status did not impact initial efficacy; complete remission rates were comparable between groups (67% vs. 69%). However, PPM1D mutations were significantly associated with inferior progression-free survival (PFS) (median PFS: 6 months vs. 16 months, p = 0.04). Regarding toxicity, the mutated subgroup exhibited significantly higher rates of grade ≥2 cytokine release syndrome and a trend toward increased neurotoxicity (25% vs. 7%). Conclusions: PPM1D clonal hematopoiesis is frequent in RRMM and despite deep initial responses, patients harboring PPM1D mutations face a significantly higher risk of early relapse. PPM1D mutations may serve as a biomarker for poor durability of response and should be further evaluated in larger, prospective trials. Full article

Background/Objectives: Therapeutic options for patients with relapsed and refractory multiple myeloma (RRMM) have advanced substantially in recent years. In particular, T-cell-engaging therapies, including chimeric antigen receptor (CAR) T-cell therapy and bispecific antibodies (bsAbs), have emerged as highly effective treatment modalities. However, data on predictive biomarkers for response to these therapies remain limited. Patients currently receiving T-cell-engaging therapies are typically heavily pretreated and frequently exhibit clonal hematopoiesis. Clonal hematopoiesis, especially involving PPM1D mutations, may adversely affect the efficacy of T-cell-engaging therapies. Methods: We conducted a retrospective, single-center study including 27 patients with RRMM who were treated with bsAbs (teclistamab, elranatamab, or talquetamab) between June 2022 and September 2025 and for whom genetic material was available before bsAB treatment. We evaluated the impact of PPM1D mutations on treatment response, progression-free survival (PFS), and overall survival (OS). Results: The prevalence of PPM1D mutations in our cohort was 27%. Compared with patients without PPM1D mutations, mutation carriers showed a trend toward less deep remissions and demonstrated significantly inferior 6-month PFS (43% vs. 85%, p = 0.0272) and 6-month OS (57% vs. 90%, p = 0.0473). Conclusions: These findings suggest that PPM1D mutations may represent a promising biomarker in patients with RRMM treated with bsAbs. Larger, prospective studies are warranted to validate and further elucidate these observations. Full article

Background/Objectives: Tezepelumab targets thymic stromal lymphopoietin and has broad efficacy in severe asthma, yet real-world evidence on patient-reported trigger burden remains limited. We assessed 12-month outcomes after tezepelumab, focusing on clinical remission, biomarkers, and trigger profiling as complementary dimensions of response. Methods: In this multicenter longitudinal real-world observational cohort based on routine clinical follow-up and Severe Asthma Network in Italy (SANI) registry data, 43 adults with severe asthma treated with tezepelumab at four Italian SANI reference centers were evaluated at baseline and, when available, after 1, 3, 6, and 12 months. Outcomes included exacerbations, lung function, type 2 biomarkers, the Asthma Control Test, SNOT-22, trigger categories, Asthma Trigger Inventory (ATI) scores, and SANI-defined clinical remission. Results: Among 22 patients with 12-month follow-up data, mean annualized exacerbations decreased from 4.30 ± 2.77 to 0.36 ± 0.49 (p < 0.001), and 14/22 (63.6%) were exacerbation-free. Asthma control improved, whereas FEV1 remained stable. FeNO and blood eosinophils decreased at selected time points. The number of reported trigger categories was lower at 6 months (p < 0.001), and physical exertion, smoke, irritants, and infection-related ATI domains improved longitudinally. Complete clinical remission was achieved in 5/22 patients (22.7%). Conclusions: Tezepelumab was associated with reduced exacerbations, improved asthma control, and lower patient-reported trigger burden. Structured trigger profiling may provide an exploratory patient-centered dimension for assessing treatment response in severe asthma. Full article

Chronic myeloid leukemia (CML) represents a paradigm of targeted therapy, driven by the BCR::ABL1 fusion kinase. Over the past four decades, therapeutic strategies have evolved from early molecular targeting approaches and interferon-α to tyrosine kinase inhibitors (TKIs), dramatically improving survival and transforming CML into a largely controllable disease. To provide a comprehensive overview of this evolution, we conducted a narrative literature search across the PubMed and Embase databases, selecting peer-reviewed articles, international guidelines, and landmark clinical trials based on their historical and clinical relevance. Through this expert-driven synthesis, focusing on key milestones in CML therapy, including antisense strategies, interferon-based treatment, first-, second-, and third-generation TKIs, and the development of allosteric inhibitors, this paper analyzes current management strategies, treatment-free remission (TFR), and emerging therapies. The introduction of imatinib established proof of principle for oncogene-targeted therapy, leading to sustained survival improvements. Second- and third-generation TKIs further enhanced response depth and addressed resistance, including the T315I mutation. More recently, the development of the allosteric inhibitor asciminib introduced a novel mechanism of action and expanded therapeutic options for pretreated patients. Furthermore, the achievement of deep molecular responses has enabled TFR in approximately 40–60% of selected patients, redefining treatment goals toward functional cure. Emerging agents, including next-generation ATP-competitive and allosteric inhibitors, are showing promising activity in resistant disease and may further improve outcomes. Thus, CML represents a unique model of translational oncology, demonstrating how mechanistic insight can drive therapeutic innovation. Future strategies will focus on increasing TFR rates, overcoming resistance, targeting leukemic stem cells, and improving global access to therapy and monitoring, with the ultimate aim of achieving functional cure in the majority of patients. Full article

Epcoritamab, a subcutaneous CD3×CD20 bispecific antibody, has shown substantial activity in relapsed or refractory (R/R) B-cell lymphomas, but the immunological correlates of durable remission and treatment discontinuation remain unclear. We retrospectively analyzed 21 consecutive patients who initiated epcoritamab at our institution between 1 December 2023 and 31 December 2025, including 17 with R/R large B-cell lymphoma (LBCL) and 4 with R/R follicular lymphoma (FL). Clinical follow-up was updated through 18 May 2026. Serial cytotoxic T lymphocyte (CTL) subset and T-cell receptor (TCR) Vβ repertoire analyses were performed in selected cases. Among response-evaluable patients, the overall response rate was 9/14 in LBCL and 4/4 in FL. Median overall survival was 431 days in LBCL and 431.5 days in FL. Progression-free survival was analyzed descriptively because of the small sample size and substantial censoring. A patient with clinically and radiologically suspected central nervous system relapse of LBCL achieved radiological complete remission after epcoritamab treatment. In two LBCL and one FL case in whom epcoritamab was electively discontinued after complete remission, Vβ-skewed CTL populations were observed, and total memory CTLs exceeded total effector CTLs at discontinuation. These exploratory findings suggest that epcoritamab treatment may be associated with longitudinal remodeling of CTL subsets and Vβ-skewed CTL populations in selected responders. The potential relevance of these immunological patterns to durable response and treatment discontinuation should be validated in larger prospective cohorts with functional and sequence-based T-cell analyses. Full article

Hematological malignancies encompass a broad spectrum of relatively rare cancers with diverse biological and clinical characteristics that are capable of affecting individuals across all age groups, though certain subtypes show a predilection for specific age ranges. Advances in next-generation sequencing have greatly enhanced our understanding of the molecular and genetic basis of these diseases, while epigenetic, transcriptional, and proteomic analyses have further clarified their pathogenesis. These developments have shaped the classification and treatment of lymphoma. Updated classification frameworks which include the identification of clinically relevant molecular targets have opened the door to a number of targeted agents, each designed to exploit specific vulnerabilities within malignant cells, while stem cell transplantation continues to offer curative potential for eligible patients, with improving safety profiles over time. CAR-T-cell therapy has been extended to multiple blood cancer indications, achieving lasting remissions in patients with previously exhausted treatment options. Bispecific antibodies have further broadened the immunotherapy landscape by redirecting the body’s own T cells against tumor cells, offering a readily available alternative that overcomes many of the practical limitations associated with CAR-T-cell production. The ability to combine these strategies has fundamentally changed what is achievable in blood cancer treatment, with long-term remission now a realistic goal for many patients. This review seeks to outline the core molecular mechanisms underlying lymphoma and leukemia, evaluate currently approved treatment options, discuss significant ongoing clinical trials with practice-changing potential, and explore the prospect of chemotherapy-free approaches in carefully selected patient groups. Full article

Background: Relapse is the leading cause of treatment failure in patients with myeloid hematologic malignancies undergoing allogeneic hematopoietic cell transplantation. Clonal genomic evolution may contribute to post-transplant relapse, yet its determinants and prognostic impact remain incompletely characterized. Methods: In this retrospective study, we analyzed 63 patients with myeloid neoplasms who underwent cytogenetic evaluation both at diagnosis and at relapse after allogeneic hematopoietic stem cell transplantation. Cytogenetic changes (CGE), including evolution, devolution, or combined patterns, were assessed and correlated with clinical characteristics, prior treatment exposure, and survival outcomes. Results: Cytogenetic changes were observed in 46.1% of patients. The presence of cytogenetic changes (CGE) was strongly associated with the presence and complexity of cytogenetic abnormalities at initial diagnosis, whereas prior chemotherapy exposure, conditioning intensity, and donor type showed no significant association. Patients with cytogenetic changes had a lower complete remission rate at day 30 after transplantation; however, relapse-free survival and post-relapse survival did not differ significantly between groups. Conclusions: These findings suggest a potential association between post-transplant cytogenetic changes and intrinsic genomic instability, although treatment-related effects cannot be excluded. Larger, disease-stratified studies integrating cytogenetic and molecular analyses are warranted to further clarify the biological and prognostic relevance of clonal evolution following transplantation. Full article