Current oncology最新文献

The role of Signal Transducer and Activator of Transcription 2 (STAT2) in cancer remains poorly understood. STAT2 is a key mediator of type I interferon (IFN) signaling, activating the expression of IFN-stimulated genes with antiviral and antiproliferative effects. However, emerging evidence suggests that STAT2 can also promote tumor growth. Here, we show that high STAT2 mRNA expression in colon cancer tumors correlates with reduced overall survival in patients. In preclinical models, deletion of STAT2 in tumor cells suppressed tumor growth, whereas STAT2 overexpression enhanced tumor growth, supporting its pro-tumorigenic role. To determine whether this function depends on type I IFN receptor (IFNAR1) signaling, we generated IFNAR1 knockout (IFNAR1 KO) colon carcinoma cells and compared their growth with parental and STAT2-deficient (STAT2 KO) tumor cells. Loss of type I IFN signaling was confirmed by western blot and qPCR analyses. In vitro, IFNAR1 KO and STAT2 KO tumor cells proliferated at similar rates. However, in xenograft tumor transplantation models, IFNAR1 KO cells formed larger tumors while STAT2 KO tumor cells formed smaller ones compared to parental tumor cells. These findings indicate that STAT2 promotes colorectal cancer growth through mechanisms independent of IFNAR1 signaling.

Objective: CDK4/6 inhibitors constitute standard first-line therapy for hormone receptor (HR)-positive, HER2-negative metastatic breast cancer (MBC). We investigated real-world predictors of overall survival (OS), with particular focus on high ER expression (≥90%).

Methods: In this multicenter, retrospective study, we analyzed 603 HR-positive/HER2-negative MBC patients treated with CDK4/6 inhibitors (ribociclib or palbociclib) between May 2020 and June 2024. We evaluated demographic, clinical, and pathological factors for their impact on OS using univariate and multivariate Cox regression analyses.

Results: In univariate analysis, significantly longer OS was observed in endocrine therapy-naive patients (median OS: 51.0 vs. 33.3 months; p < 0.001), those without liver metastases (50.0 vs. 34.0 months; p = 0.019), bone-only metastases (57.7 vs. 40.5 months; p = 0.022), and PR-positive patients (50.0 vs. 36.0 months; p = 0.037). Patients with ER expression ≥90% showed a strong trend toward longer OS (49.0 vs. 41.0 months; p = 0.072). In multivariate analysis, endocrine therapy naivety (p = 0.045) and high ER expression (≥90%) (p = 0.031) emerged as independent predictors of superior OS.

Conclusions: Our study identifies treatment naivety and exceptionally high ER expression (≥90%) as key independent predictors of prolonged OS in CDK4/6 inhibitor-treated MBC patients. These findings underscore the importance of early CDK4/6 inhibitor implementation and suggest that quantitative ER assessment may refine patient selection beyond conventional positivity thresholds.

Cancer-related fatigue (CRF) is prevalent and onerous for cancer survivors. Not all survivors respond equally to interventions, but the characteristics distinguishing responders and non-responders are often unknown. This secondary analysis study compared baseline characteristics for responders (CRF reduction ≥2 points), non-responders, and those lost to follow-up using data from a two-group pre-test/post-test trial of a four-week exercise intervention compared to usual care. Included were 278 adult cancer survivors, with a mean age of 52.2 ± 11.9, 65% (180/278) female, and 90% (250/278) Caucasian. Of these, 77 (28%) were responders, 153 (55%) were non-responders, and 48 (17%) were lost to follow-up. At baseline, participants completed the 6-item Schwartz Cancer Fatigue Scale, with responses from 1 (not at all) to 5 (extremely fatigued) and a total score ranging 6-30. In the intervention group, 35% (49/141) reported decreased fatigue, 24% (34/141) reported increased fatigue, 25% (35/141) had minimal change, and 16% (23/141) were lost to follow-up. In the control group, 20% (28/137) reported decreased fatigue, 39% (53/137) reported increased fatigue, 23% (31/137) had minimal change, and 18% (25/137) were lost to follow-up. Responders in both groups reported higher baseline fatigue than non-responders, with mean differences of 5.2 (95% CI: 3.6-6.8) and 5.4 (95% CI: 3.4-7.3) for intervention and usual care, respectively. Higher baseline fatigue was found in responders compared to non-responders, regardless of group assignment, suggesting that those with a greater fatigue burden may have derived more benefit from exercise for CRF or a regression to the mean effect.

Background: Carriers of a pathogenic variant (PV) in BRCA1 face a high risk of breast cancer. This study estimated the risk of developing breast cancer according to mutation type and location.

Methods: BRCA1 carriers with no personal history of breast cancer or bilateral mastectomy were included. Detailed information on clinical and family history was collected by questionnaire. Survival analysis was used to estimate 15-year cumulative risk according to PV type and location.

Results: A total of 3677 BRCA1 carriers were followed for a mean of 7.2 years (range 0.1-15.0 years); 481 incident breast cancers were documented. Overall, the 15-year cumulative incidence was 25%. Risk estimates varied by exon, ranging from 9% (exon 21) to 19% (exon 12) to 36% (exon 15); however, strata were small. Carriers of four founder mutations common in Eastern Europe (c.5263_5264insC, c.181T > G, c.66_67delAG and c.4034delA) experienced a lower-than-expected cancer risk (15.9-24.4%) compared to other PVs (28.8%) (p = 0.02).

Conclusions: Although our data suggests some variability in penetrance based on specific BRCA1 PV, this was based on a large number of founder mutations. Breast cancer management strategies should continue to be based on comprehensive risk assessment.

Background: Healthcare communication often relies on complex digital infrastructures, yet clinicians increasingly adopt general-purpose Instant Messaging Apps (IMAs) such as WhatsApp^® to meet unmet needs. DonnaRosa, an Italian community of breast cancer specialists founded in 2017, is a Community of Practice (CoP), where experts exchange second opinions, guidelines, and trial opportunities. This paper examines its origins, practices, and implications. Methods: A mixed-methods design was applied: (1) qualitative analysis of chat logs to identify interaction patterns and rules; (2) a 2024 online survey of 54 members (92.5% response rate) exploring demographics, usage, and perceived value; (3) ongoing semi-structured interviews with founders and participants to reconstruct history, recruitment, and professional impact. Results: The group has grown through personal invitations, creating a friendly network of oncologists. Communication is concise, colloquial, and collegial. Activities focus on case discussions, reassurance, interpretation of guidelines, and exchange of research opportunities. This article presents data from an online survey conducted in 2024, showing that the group is widely used for second opinions, often consulted even on weekends and holidays, and perceived as a source of professional support and learning. Members report that participation frequently changes or refines their clinical judgement, especially when guidelines are incomplete or ambiguous. The community also promotes resilience, reduces professional isolation, supports informal collaboration in research projects, and encourages interaction on organisational and healthcare management issues. Conclusions:DonnaRosa illustrates how informal IMAs can evolve into robust infrastructures of care and professional solidarity, complementing formal systems. In the era of artificial intelligence, CoPs like DonnaRosa may become even more relevant: AI tools, especially large language models, can accelerate literature retrieval and data synthesis, while the CoP provides the critical, experience-based interpretation needed for safe and meaningful application. Such a dual infrastructure-technological and human-offers a promising path for oncology, where complexity requires both computational breadth and the depth of expert clinical judgement. Taken together, these findings and the evolving role of AI in clinical communication underscore the need for oncology societies to develop governance frameworks that ensure the safe, accountable, and clinically appropriate use of instant-messaging tools in professional practice.

Soft tissue sarcomas (STS) are rare and heterogeneous tumors for which achieving complete tumor resection with negative surgical margins remains the cornerstone of curative treatment and a key predictor of survival. Current intraoperative resection margin status assessment techniques remain limited, as traditional intraoperative frozen section analysis is of limited accuracy for most STS histological subtypes. This comprehensive review evaluates current and emerging margin assessment techniques used intra-operatively during STS resection. A systematic search of PubMed and PubMed Central databases from 2000 to 2025 identified studies using fluorescence imaging, spectroscopy, and ultrasound-based modalities. Indocyanine green (ICG) fluorescence-guided surgery appeared to be the closest to widespread use, with the most clinical evidence showing potential to reduce positive margins. Use of acridine orange (AO) as a fluorescent dye also showed potential in decreasing local recurrences, but it remains in the experimental stage of research with little clinical data available. Raman spectroscopy has recently shown high accuracy in identifying STS from healthy tissue, but the impact of its use on patient outcomes has not been studied yet. Other techniques, such as diffuse reflectance spectroscopy (DRS), rapid evaporative ionization mass spectrometry (REIMS), optical coherence tomography (OCT), and intraoperative ultrasound (IOUS) yielded encouraging results but still require further prospective studies to validate their safety, reproducibility, and clinical utility in improving surgical precision and patient outcomes.

Adrenocortical carcinoma (ACC) is a rare and aggressive cancer with limited treatment options, commonly managed with mitotane, which can cause serious side effects, including central hypothyroidism and dyslipidemia. This study aimed to evaluate the incidence, clinical features, and relationship between mitotane-induced central hypothyroidism and dyslipidemia in ACC patients, as well as to investigate mitotane's direct toxic effects on thyroid cells. Thirty-eight ACC patients treated with mitotane for at least six months were monitored for thyroid function and lipid profiles. Central hypothyroidism developed in 50% of patients with normal baseline thyroid function, mostly women, who were at higher risk. Dyslipidemia occurred in 40% of patients, more frequently in men, and appeared earlier than hypothyroidism. In vitro experiments on rat thyroid cells demonstrated a dose-dependent toxic effect of mitotane on cell viability. No significant link was found between hypothyroidism and dyslipidemia risk. These findings reveal sex-specific susceptibilities to mitotane toxicity and provide novel evidence of direct mitotane-induced thyroid cell damage. This insight supports the need for careful thyroid and lipid profile monitoring during mitotane treatment and may inform the development of safer therapies for ACC.

Post-surgical pyoderma gangrenosum is a rare neutrophilic dermatosis that may occur after surgical procedures, mimicking a wound infection. Early recognition is crucial to prevent unnecessary debridement and worsening of lesions due to pathergy. We report the case of a 67-year-old woman who underwent nipple-sparing mastectomy for invasive breast carcinoma with immediate reconstruction using a tissue expander. In the early postoperative period, she developed an extensive sterile necrotic-ulcerative inflammation of the left breast, unresponsive to broad-spectrum antibiotics and repeated surgical revisions. Histopathology revealed an aseptic neutrophilic infiltrate, confirming the diagnosis of post-surgical pyoderma gangrenosum. The patient responded favorably to high-dose corticosteroid therapy, achieving complete wound healing and definitive reconstruction with a TRAM flap. This case highlights the importance of considering post-surgical pyoderma gangrenosum in the differential diagnosis of inflammatory postoperative complications in breast oncology surgery. Prompt diagnosis and early initiation of immunosuppressive therapy within a multidisciplinary approach are key to preserving tissues and ensuring optimal functional and aesthetic outcomes.

Immune checkpoint inhibitors (ICIs) have reshaped melanoma care, yielding durable remissions even in high-risk stages. As survival improves, fertility becomes a key survivorship concern for young women, yet the reproductive safety of ICIs remains insufficiently characterised. We performed a SWOT (Strengths, Weaknesses, Opportunities, Threats) analysis synthesizing preclinical and clinical evidence to evaluate the rationale for fertility preservation (FP) prior to checkpoint inhibitor therapy. Preclinical models of PD-1/CTLA-4 blockade demonstrate ovarian immune activation, cytokine release (e.g., TNF-α), and follicular loss. Conversely, human data are limited to correlative analyses suggesting potential declines in ovarian reserve markers. In conclusion, while prospective studies are required to definitively quantify risk, proactive fertility preservation counselling should be routinely offered prior to treatment initiation to safeguard reproductive autonomy without compromising oncologic safety.

Bladder cancer is the 5th most common cancer in Canada and a quarter of diagnosed patients have muscle-invasive bladder cancer (MIBC). Standard treatment options, systemic therapy and radical cystectomy (RC) are associated with high rates of adverse outcomes. Recently, trimodal treatment (TMT), a bladder preservation strategy defined as maximal transurethral resection of bladder tumor (TURBT) and chemoradiation, has been considered an alternative per guidelines for select patients who prefer bladder preservation or those with comorbidities. Nevertheless, the uptake of bladder preservation strategies in Canada remains low. We conducted a retrospective evaluation in British Columbia (BC) to assess the real-world outcomes of bladder-sparing radiotherapy. Cohort treated with combined chemoradiotherapy (concurrent and/or adjuvant, neoadjuvant chemotherapy) showed numerical improvements across all evaluated endpoints, including disease-specific survival and progression-free survival, compared with radiation therapy alone, which is generally considered an inferior strategy. However, these differences did not reach statistical significance, contrasting with the literature. Despite the limitations posed by the small sample size and the study's retrospective design, the findings highlight the pivotal role of appropriate patient selection in achieving meaningful therapeutic outcomes. Future studies integrating biomarker-driven strategies are needed to enhance outcomes through individualized treatment selection, particularly for older patients with multiple comorbidities.