Tumori Journal

Soft tissue and bone sarcomas may carry a considerable symptom burden, which typically worsens in the final weeks of life. To help clarify personalized palliative care needs, we investigated discrepancies in end-of-life management between patients with sarcoma and those with the most common carcinomas.

This retrospective cohort study enrolled all sarcoma patients who died between 1 January 2018 - 31 October 2023, either in the palliative care unit or in medical oncology units, at a large cancer hospital in northern Italy. Each patient with sarcoma was matched with up to three randomly selected patients with carcinoma. Matching was based on age, year of death and unit. Electronic health records were reviewed.

Thirty-six patients with sarcoma were matched with 96 patients with carcinoma (44 lung cancer, 40 breast cancer and 12 colorectal cancer). Patients with sarcoma had a significantly higher chance of palliative sedation compared with patients with carcinoma (OR=32.5). The most common refractory symptom in patients with sarcoma was dyspnea (50%), followed by pain (26%). The average opioid dose difference between patient groups during sedation was as high as 220 mg. The final recorded Richmond Agitation-Sedation Scale score (RASS) was on average -4.4 for patients with sarcoma who died in hospice compared to -2.5 for those who died in an oncology unit.

In our series, patients with sarcoma had a substantially higher risk of experiencing refractory symptoms requiring palliative sedation compared to patients with the most common cancers. Pain and dyspnea were the most common refractory symptoms in patients with sarcoma, resulting in higher dosages of opioids and possibly impacting sedation deepness. This study suggests that patients with sarcoma may pose special challenges to end-of-life care.

Synovial sarcoma (SS) is molecularly defined by the pathognomonic SS18::SSX fusion, a master epigenetic driver. While NTRK gene fusions are high-priority tissue-agnostic targets for TRK inhibitors like larotrectinib, their co-occurrence with established lineage-defining drivers in sarcomas is exceptionally rare and presents a therapeutic paradox.

A 78-year-old female was diagnosed with metastatic biphasic SS. Molecular profiling via targeted RNA sequencing identified a pathogenic PDE3A-NTRK2 fusion (Tier 1A) alongside the canonical SS18 rearrangement. Despite the presence of this usually actionable target, second-line treatment with larotrectinib resulted in rapid clinical deterioration and "explosive" tumor growth, signifying absolute primary resistance to TRK inhibition. The disease followed an aggressive course typical of chemorefractory SS, leading to the patient's death ten months after initial diagnosis.

This case provides critical clinical evidence of the "driver versus passenger" phenomenon in precision oncology. It demonstrates that the epigenetic dominance of the SS18::SSX fusion can override the therapeutic relevance of a concurrent NTRK fusion. Our findings serve as a cautionary note: actionable targets detected via next-generation sequencing must be interpreted within the tumor’s canonical biological context, as lineage-defining translocations may render secondary kinase alterations therapeutically inert.

Issues related to end-of-life decisions (ELDs) generate impassioned debates in society. Our study aimed at investigating attitudes in care of cancer patients at the end-of-life (EOL); ascertaining the opinion of healthcare professionals (HCPs), patients, and caregivers.

An anonymous and self-administered questionnaire was delivered to HCPs (physicians, nurses, psychologists, and social workers), patients and family caregivers at Veneto Institute of Oncology, Italy, and 425 questionnaires were collected (136 HCPs, 171 patients, 118 caregivers).

Withholding life-sustaining treatment (LST) was declared by 11.3% of physicians and nurses and withdrawing by 19.4%, whereas 46.8% declared starting LST, and 48.4% did not discontinue LST. Most HCPs (75.7%) were in favor of patient's right to anticipate EOL, and 86.4% of withholding/withdrawing LST upon patient's request, with 62.4% HCPs agreeing on lethal drug doses to be allowed upon request of the patient. The majority (80.1%) disagreed that “life is an unavailable asset and there is no right to die”. For patients and caregivers, in ELDs greater value was given to self-determination first, with family members and trustees’ subsequent involvement. A considerable number of HCPs reported feeling inadequate to communicate bad news.

Despite the limitations imposed by the cross-sectional nature, this study adds information with regard to EOL in oncology setting in Italy. Our study shows that an attitude to prolonging patient's life in ELDs is still prevalent among HCPs in an Italian oncological setting, although there are signs of change. Communicating bad news emerges as an issue, along with HCPs’ awareness that they need more education and training.

Alectinib, a second-generation ALK inhibitor, is used in first-line and adjuvant treatment for ALK-rearranged NSCLC, and has proven to be both effective and well tolerated. Gastrointestinal (GI) perforation is an extremely rare but potentially life-threatening complication, with only sporadic cases reported in the literature.

We describe, to the best of our knowledge, the largest case series to date of GI perforations that occurred during alectinib treatment in patients with ALK-rearranged NSCLC. Clinical features, management strategies, and outcomes were analyzed and integrated with available literature.

Three female patients developed GI perforation after variable durations of alectinib treatment, ranging from one month to over three years. Two cases were associated with pre-existing diverticulosis, while one occurred in the absence of any known GI comorbidities. Management included conservative treatment with intravenous antibiotics in two cases and surgical intervention in one. Alectinib was permanently discontinued in all patients. Subsequent therapeutic strategies included lorlatinib or brigatinib, with heterogeneous tolerability and outcomes. Literature review identified other reports of GI perforation or severe toxicity under alectinib.

Although rare, GI perforation, represents a clinically relevant adverse event associated with alectinib, particularly in patients with diverticulosis or other predisposing conditions. It is essential to optimize safety and long-term disease control by raising awareness of early warning symptoms, conducting a baseline GI evaluation in high-risk patients and carefully sequencing therapy after discontinuation.

Chemo–immunotherapy is the standard frontline treatment of advanced non–squamous non–small cell lung cancer (nsq–NSCLC). Among oncogenic drivers, KRAS mutation accounts for approximately 25% of lung adenocarcinomas, with p.G12C being the most common variant. This study assessed clinical features and survival outcomes according to KRAS mutation in a real–life population of nsq–NSCLC patients treated with first–line platinum–pemetrexed–pembrolizumab.

This is a retrospective–prospective study including patients with nsq–NSCLC who received first–line platinum–pemetrexed–pembrolizumab from 4 September 2018 in 33 Italian Centers.

Among the 765 patients included in this analysis, 121 (15.8%) had KRAS p.G12C mutation, 201 (26.3%) KRAS non–p.G12C mutation and 443 (57.9%) KRAS WT. KRAS–mutated patients had more frequently a history of smoking (90.6% vs 84.1%, p=0.012) and bone metastases (44.1% vs 35.9%; p=0.022) compared to KRAS WT.

Median Overall Survival (OS) was similar between KRAS–mutated and KRAS WT patients (16.7 vs 18.2 months; adjusted Hazard Ratio [HR] 1.19, 95% Confidence Interval [CI] 0.95–1.50, p=0.132). No difference in OS was found between KRAS p.G12C and KRAS non–p.G12C (15.9 vs 17.0 months, HR 0.93, 95% CI: 0.66–1.31, p=0.676).

Median progression–free survival was significantly shorter in KRAS–mutated compared to KRAS WT patients (8.8 vs 10.8 months; adjusted HR 1.29, 95% CI 1.04–1.59, p=0.018), with no differences between KRAS p.G12C and KRAS non–p.G12C (8.8 vs 8.8 months, HR 0.95, 95% CI: 0.70–1.30, p=0.756).

KRAS mutation showed a potential negative predictive role in advanced nsq–NSCLC treated with first–line chemo–immunotherapy. The impact of co–mutations and post–progression outcomes warrants further investigation.

This pilot study aimed at evaluating the feasibility and acceptability of a structured psycho-educational intervention designed to increase disease awareness in children with tumors. The primary objective was to promote psychological adjustment by supporting children’s understanding of their illness and facilitating open parent–child communication about cancer.

Consecutive patients aged 6–11 years undergoing diagnosis or treatment for tumors at a single pediatric oncology center were invited to participate in a four-month period. The intervention consisted of three stages: (1) development of a mini guidebook for caregivers; (2) a psychologist-led meeting with parents focused on communication strategies; and (3) individual or group educational activities with children conducted by a multidisciplinary team. Child-centered, age-appropriate methods—including play, creative tasks, and anonymous “empty speech bubbles” for questions—were used to address disease etiology, diagnostic procedures, treatments, and terminology.

Eleven children participated in the intervention. All engaged actively in the sessions and expressed reassurance and satisfaction with the information received. The use of anonymous question tools facilitated open expression of fears and doubts. Parents reported increased confidence and reduced difficulty in communicating with their child about the illness, valuing the structured guidance provided.

This preliminary experience suggests that structured, interactive interventions promoting illness awareness are feasible and well accepted in pediatric oncology. Such approaches may support psychological adjustment in children with tumors and improve parent-child communication, representing a valuable component of holistic cancer care.

Liquid biopsy has emerged as a valuable tool for detecting therapeutic targets and resistance mechanisms. This study evaluated the analytical performance and clinical utility of TruSight Oncology 500 ctDNA (TSO500) compared to the FDA-approved Guardant360 CDx (G360) in detecting actionable alterations in non-small cell lung cancer (NSCLC) patients progressing on targeted therapies.

We analyzed 44 plasma samples from 36 consecutive metastatic NSCLC patients with known molecular drivers (EGFR and BRAF mutations, ALK and RET fusions) progressing on targeted therapy. The comparative analysis included 31 paired samples from 27 patients. Valid results were obtained from G360 in 42/44 cases (95.45%) and TSO500 in 32/44 samples (72.8%).

TSO500 demonstrated high sensitivity for G360-identified variants (81.02% overall; 85.26% for pathogenic/likely pathogenic variants). Concordance was particularly high for ESCAT I alterations (95.2% sensitivity), including 100% sensitivity for gene fusions (five detected fusions). TSO500 identified 102 additional variants not detected by G360. Among nine patients with concurrent tissue biopsy, TSO500 detected 16 potentially actionable mutations absent in tissue samples. Both assays identified resistance mutations in 12/26 patients (46.2%), with TSO500 detecting all but three G360-identified alterations. High correlation was observed between variant allele frequencies (Pearson's r = 0.89).

TSO500 demonstrates high concordance with G360 for detecting actionable alterations and robust fusion identification. Its ability to detect additional variants and resistance mutations not found in tissue highlights its potential value in guiding personalized treatment decisions for NSCLC patients.

This retrospective single-center observational study aimed to describe our experience of admitting patients based on palliative care needs rather than discontinuation of anticancer treatment.

The study included all cancer patients admitted to Valerio Grassi Hospice while receiving disease modifying therapies (DMTs) in 2022. Functional status was assessed using the Eastern Cooperative Oncology Group Performance Status (ECOG PS) and the Palliative Prognostic Score (PaP score).

Thirty-one of the 150 included patients received DMTs in the last 30 days of life. Among these, five (16.1%) had an ECOG PS 2, 10 (32.3%) ECOG PS 3, and 16 (51.6%) ECOG PS 4. PaP scores were 0–5.5 in three patients (9.7%), 5.6–11 in 14 (45.2%), and 11.1–17.5 in eight (25.8%).

Our findings confirm the ongoing use of DMTs in terminally ill patients and highlight their unmet need for palliative care. Including such patients into hospice programs may help avoid futile aggressive treatments, improve care appropriateness, and ensure better quality of life at the end of life.

Chemo-immunotherapy (CT-IT) currently represents the standard therapy for both non-small (NSCLC) and small cell lung cancer (SCLC). However, the differential impact of platinum compounds on immunotherapy outcomes remains to be determined.

A systematic review was conducted to identify randomized controlled trials (RCTs) of combinations of immune check-point inhibitors (ICIs) and platinum-based chemotherapy (CT), providing separate outcome data for carboplatin and cisplatin. Since no direct comparison between the two platinum compounds was reported, a network meta-analysis was performed. The primary endpoints were overall survival (OS) and progression-free survival (PFS) for advanced NSCLC and SCLC and event-free survival (EFS) for early-stage NSCLC.

Eleven RCTs including 6125 patients were analyzed. In extensive-stage SCLC (four trials, 2663 patients), a non-significant trend toward improved OS was observed with cisplatin-based regimens (HR: 0.92, 95% CI 0.72–1.18; I²=47%). In advanced NSCLC (four trials, 1948 patients), a non-significant trend toward improved PFS was observed with carboplatin-based regimens (cisplatin vs carboplatin HR: 1.11, 95% CI 0.89–1.39; I²=0%). In early-stage NSCLC (three trials, 1514 patients), no differences emerged in EFS between subgroups (p=0.65 fixed-effect; p=0.49 random-effects).

Our analysis does not demonstrate a statistically significant difference between cisplatin- and carboplatin-based CT-IT in lung cancer, although stage- and histology-specific numerical trends were observed. Given the absence of head-to-head comparisons and the lack of disaggregated baseline data, these findings should be considered exploratory.

The old oncology approach, which considered the clinical and performance status as the most relevant diseases course and well-being indexes, has been recently replaced by a care system also focusing on a person’s characteristics and needs. This study analyzed the role of physical symptoms, illness awareness, individual activities and social contexts on anxious/depressive symptoms and mental health in localized (LP) and advanced/metastatic (AMP) cancer patients.

Socio-demographic and medical information was gathered. The Revised Illness Perception Questionnaire, Hospital and Depression Anxiety Scale, and Mental Health Continuum Short-Form were administered.

One hundred and thirteen patients, 75 LP and 38 AMP, aged 27-82, were enrolled. Unique patterns of difficulties and resources emerged at different stages of cancer. AMP reported a worse quality of life in perceived illness persistence and treatments control, anxious/depressive symptoms, and psychological well-being. In LP, higher levels of anxious/depressive symptoms were associated with lack of hobbies, and higher perceived illness control was linked to higher mental health. LP did not report higher well-being than AMP. No significant differences in flourishing persons distributions were detected among groups. A multivariable model showed that the independent presence of pain and partner influenced higher levels of mental health more in AMP than in LP.

Tailored intervention should enhance individuals’ mental health and active resources mobilization.

While artificial intelligence (AI) is known to benefit radiotherapy (RT), its applications in carbon ion RT (CIRT) is yet to be surveyed. This scoping review aims to examine the current landscape of AI in CIRT and highlight future directions.

Following PRISMA guidelines, three databases (PubMed, Scopus, and Web of Science) were searched to find eligible English articles investigating AI in CIRT between January 2014 and June 2025. Two human reviewers and an AI tool independently screened articles. Agreement was quantified using Cohen’s kappa and McNemar’s test (α = 0.05).

Of the 413 unique articles screened, 16 were selected, and an additional three were included through citation search, totaling 19 articles. The screening agreement between human and AI reviewers was substantial (Cohen’s kappa = 0.75) with no statistical difference (p = 0.18). The AI contributions in CIRT were categorized into treatment planning, optimization, and verification; synthetic imaging; tumor control; and normal tissue complication prediction. All selected studies were limited by small datasets and lacked external validation.

AI development in the CIRT domain is in early stages but holds promise for reducing costs and improving treatment, especially in adaptive settings. Future efforts should foster collaboration across CIRT facilities to support robust AI applications.