AC Camargo Hospital

This study aimed to evaluate the effect of blue light therapy on tumor behavior and cancer stem cells properties in oral squamous cell carcinoma (OSCC). The OSCC cell lines SCC9 and HSC3 were exposed to blue light irradiation at 105, 168, and 210 J/cm². After 24 h, cell viability was evaluated using MTS and crystal violet assays. Apoptosis and necrosis were analyzed by Annexin V and DAPI staining through flow cytometry; migration was assessed by wound-healing assay; and cancer stem cells properties were examined by colony and sphere formation assays, RT-qPCR for cancer stem cells biomarkers (BMI1, CD44, OCT4, NANOG), and flow cytometry for CD44 and ESA expression. Blue light irradiation reduced cellular viability in both cell lines and increased apoptosis in SCC9 cells, while no change was observed in HSC3. Blue light irradiation significantly decreased migration in both cell lines. Regarding cancer stem cells characteristics, blue light reduced colony formation in SCC9 at 105 and 210 J/cm² and sphere formation in both cell lines. Expression of BMI1, OCT4, NANOG, and CD44 genes was not altered, as well as the frequency of CD44high/ESAhigh cells. However, at 210 J/cm², SCC9 showed an increase in CD44low cells, associated with a more differentiated phenotype. Blue light irradiation reduced viability and migration in both OSCC cell lines and induced apoptosis only in non-metastatic SCC9 cells. Blue light exerted anti-tumor effects without promoting cancer stem cells properties, while decreasing their ability to self-renew.

Human papillomavirus (HPV)-driven oropharyngeal squamous cell carcinoma (OPSCC) has emerged as a biologically distinct entity, typically affecting younger, non-smoking patients and showing improved survival compared to HPV-negative tumors. Accurate HPV status determination is essential for correct staging, prognostic assessment, and treatment de-escalation. Despite advances, substantial variability persists among diagnostic methods and clinical workflows. A narrative review of PubMed, Scopus, and Web of Science databases was conducted up to July 2025. Studies addressing HPV detection techniques in OPSCC-including p16^INK4a^ immunohistochemistry (IHC), HPV DNA and RNA assays, liquid biopsy approaches, and computational surrogates-were critically analyzed regarding diagnostic accuracy, clinical applicability, and emerging innovations. Tissue-based assays remain the diagnostic reference standard. p16 IHC provides high sensitivity but limited specificity and should be confirmed with nucleic acid-based methods such as DNA PCR, in situ hybridization (ISH), or E6/E7 mRNA detection. Combined or "orthogonal" testing minimizes discordance and refines risk stratification. Liquid biopsy detection of circulating HPV DNA using droplet digital PCR or next-generation sequencing has shown high sensitivity and specificity in cohorts of patients with HPV-associated OPSCC, supporting its potential role as a complementary biomarker for treatment monitoring and surveillance. However, circulating HPV DNA alone does not unequivocally identify the anatomic source of HPV DNA and should be interpreted together with clinical, radiologic, and tissue-based findings. Oral rinse and saliva assays show moderate diagnostic performance, while artificial intelligence-based radiomic and histopathologic models are emerging as complementary tools. Reliable HPV attribution in OPSCC requires a multimodal diagnostic strategy integrating p16 IHC, molecular confirmation, and ctHPV-DNA monitoring. Methodological standardization and prospective validation are essential to implement precision-guided, cost-effective workflows in routine clinical practice.

Transoral laser microsurgery (TOLMS) is an established organ-preserving treatment for early-stage and selected intermediate-stage laryngeal squamous cell carcinoma (SCC). Initially indicated for Tis-T1 lesions, its use has progressively expanded to carefully selected T2 and T3 tumors, providing oncologic outcomes comparable to open surgery and (chemo)radiotherapy [(C)RT] while offering favorable functional results. The CO₂ (carbon dioxide) laser is the preferred device for TOLMS due to its precision and minimal thermal injury, allowing accurate tumor resection with optimal margin control. Successful application of TOLMS relies on strict patient selection and comprehensive pre- and intraoperative assessment. High-definition videolaryngoscopy, angled telescopes, bioendoscopic techniques, advanced imaging modalities, and emerging artificial intelligence tools have significantly improved the evaluation of tumor extent, biological behavior, and laryngeal function. Adequate laryngeal exposure is a critical prerequisite, as difficult exposure is associated with higher rates of positive margins and inferior oncological outcomes. Preoperative imaging, particularly magnetic resonance imaging (MRI) and dual-energy computed tomography (CT), is essential for assessing deep tumor extension, cartilage invasion, and involvement of key anatomical subsites, including the anterior commissure (AC), paraglottic space (PGS), and pre-epiglottic space (PES). AC involvement alone is not an absolute contraindication to TOLMS; however, vertical trans-AC extension and posterior PGS invasion, especially when associated with arytenoid fixation, represent major limitations due to the difficulty in achieving adequate oncologic margins. Surgical margin assessment remains challenging because of specimen shrinkage and variability in pathological evaluation, yet positive margins-particularly deep or multiple-are associated with worse disease-specific survival and laryngeal preservation. In supraglottic SCC, TOLMS is feasible for T1-T2 and selected T3 tumors, although functional outcomes decline with increasing extent of resection and patient age. The role of TOLMS in the salvage setting is limited and requires highly selective indications. In conclusion, TOLMS is an effective treatment for appropriately selected laryngeal cancers, provided that meticulous diagnostic work-up, surgical expertise, and multidisciplinary decision-making are ensured.

Introduction: Case study of woman 55-year-old, single, retired female patient who presented with a painless, slowly growing swelling in the right submandibular region for approximately 8 months, accompanied by mild dysphagia for the last two months. The absence of systemic symptoms, such as pain, fever, or weight loss, initially made the presentation clinically nonspecific. Still, the persistent swelling and its characteristics on physical examination and imaging raised strong suspicion of salivary gland neoplasia. Methods: The diagnostic process included a detailed clinical evaluation and sequential complementary exams. Initially, basic laboratory tests were performed, showing results within normal limits, except for a mild, nonspecific elevation of C-reactive protein. Imaging investigation began with an ultrasound of the cervical region, which revealed a hypoechoic, solid, and vascularized nodular mass in the right submandibular gland. A contrast-enhanced CT scan of the neck confirmed the mass, with no signs of invasion of adjacent structures or lymph node enlargement. Ultrasound-guided fine-needle aspiration biopsy was suggestive of salivary gland neoplasia, but not definitive. Results: Histopathological examination of the surgical specimen confirmed the diagnosis of adenoid cystic carcinoma of the submandibular gland, classified as low/intermediate grade. The surgical margins were considered clear, but focal perineural invasion was identified, a crucial finding due to its prognostic impact. Based on the perineural invasion, the patient was referred for adjuvant radiotherapy with the Intensity Modulated Radiation Therapy technique. Acute side effects were observed and managed during radiotherapy. Conclusion: This case of adenoid cystic carcinoma of the submandibular gland demonstrates the importance of early diagnosis and a multimodal approach in the treatment of salivary gland tumours, especially those with risk factors such as perineural invasion. The patient was successfully treated with surgery and adjuvant radiotherapy. Still, the aggressive nature and propensity of adenoid cystic carcinoma to late recurrence and distant metastases require rigorous and continuous long-term follow-up, with periodic clinical examinations and serial imaging studies (neck and chest CT scans), to monitor disease recurrence and optimise the patient's survival and quality of life.

Abstract Background: Trastuzumab deruxtecan (T-DXd), an antibody-drug conjugate targeting HER2, has shown significant clinical benefit in patients with HER2-low metastatic breast cancer. The DESTINY-Breast04 trial led to its approval in this setting, particularly among hormone receptor-positive (HR+) patients. Given its topoisomerase I inhibitor payload and DNA-damaging mechanism, tumors with homologous recombination deficiency, such as those harboring BRCA1/2 mutations, may be particularly sensitive to T-DXd. While prior studies have explored this hypothesis, the predictive role of BRCA mutations in the efficacy of T-DXd in HR+/HER2-low disease remains unclear and has not been systematically quantified. Objectives: To evaluate whether BRCA1/2 mutations are associated with improved efficacy of trastuzumab deruxtecan in patients with hormone receptor-positive, HER2-low metastatic breast cancer, by comparing objective response rate (ORR) and progression-free survival (PFS) between BRCA-mutated and BRCA wild-type populations. Methods: A systematic review and meta-analysis were conducted on June 23, 2025 according to PRISMA guidelines. Literature searches were performed in PubMed, Embase, Cochrane Library, and ASCO and ESMO websites databases. Eligible studies reported T-DXd outcomes stratified by BRCA mutation status in HR+/HER2-low metastatic breast cancer. Two reviewers independently performed study selection and data extraction. The primary endpoints were objective response rate (ORR) and progression-free survival (PFS). Analyses were performed using R software (v.4.2.2) with random-effects models. The protocol for this systematic review and meta-analysis was registered in the PROSPERO international prospective register of systematic reviews (ID: CRD420251089678). Results: A total of 3,194 records were retrieved, and after deduplication, 2,461 unique records were screened. Three studies were included: two randomized trials (DESTINY-Breast04 and DESTINY-Breast06) and one large real-world cohort (Tarantino et al., 2025). Patients with BRCA1/2 mutations demonstrated a significantly higher ORR compared to BRCA wild-type counterparts, with a pooled odds ratio of 4.48 (95% CI 1.66-12.09; I2 = 0%). For PFS, the pooled hazard ratio favored BRCA-mutated patients (HR 0.56, 95% CI 0.15-2.04), although with substantial heterogeneity (I2 = 90.3%). Conclusions: This is the first meta-analysis to evaluate the predictive impact of BRCA1/2 mutations on the efficacy of T-DXd specifically in HR+/HER2-low metastatic breast cancer. BRCA mutations appear to be associated with significantly higher response rates and a potential progression-free survival advantage. These results highlight the need to consider BRCA status as a predictive biomarker in future clinical trials of T-DXd and support its role in guiding therapeutic decisions in HER2-low disease. Citation Format: L. P. Genovez, H. J. Kim, S. M. Sanches, M. G. Cesca. Analysis of BRCA1 and 2 mutations as predictive biomarkers of response to trastuzumab deruxtecan in hormone receptor-positive, HER2-low metastatic breast cancer: a systematic review and meta-analysis [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-02-06.

Abstract Background: Obesity is an increasing concern in breast cancer, influencing both prognosis and treatment tolerance. While abemaciclib has demonstrated efficacy in high-risk HR (hormone receptor) +/HER2- patients, real-world evidence regarding its safety and efficacy across BMI (body mass index) categories remains limited. Methods: We conducted a retrospective and prospective, observational study involving 146 patients who received adjuvant abemaciclib combined with endocrine therapy between January 2021 to June 2025 at a comprehensive cancer center. Patients were stratified by BMI (kg/m2) as obese (≥30), overweight (25 ≤ BMI < 30), and non-overweight (<25). We assessed treatment-related toxicities, dose reductions, pathological response to neoadjuvant chemotherapy (RCB), recurrence, and disease-free survival. Statistical analyses included chi-square tests, Spearman correlation, Kaplan-Meier survival curves, and Cox regression. Results: Obese patients experienced higher rates of dose reduction (72%) compared to non-obese (47%) and overweight patients (29%), although the difference did not reach statistical significance (p = 0.075). Regarding neoadjuvant response, non-overweight patients achieved more RCB-0 (complete response), while 30.8% of obese patients had RCB-III (high residual disease). Although no significant association was found between BMI and RCB (p = 0.135), a clinical trend was observed. Larger tumors (>5 cm) were more frequent in obese patients (23.1%) compared to non-obese (14.3%). Anemia showed a positive correlation with BMI (Spearman p = 0.043), with a higher frequency in obese patients (27.3%) versus non-overweight (15.2%). No statistically significant associations were observed between BMI and other toxicities (diarrhea, neutropenia, transaminase elevation, arthralgia). Four recurrences were documented: three in obese and one in a non-overweight patient. Kaplan-Meier curves suggested a trend toward longer disease-free survival among obese patients (median: 641 days) compared to non-overweight patients (237 days). However, this finding did not reach statistical significance (Cox regression HR = 2.6; p = 0.235). ANOVA for time to recurrence showed a significant difference between BMI groups (p = 0.003), favoring delayed recurrence in obese patients. Conclusion: In this real-world Brazilian cohort, obesity was associated with higher rates of dose reduction due to toxicity, lower pathological response to neoadjuvant chemotherapy, and larger tumors. Paradoxically, obese patients demonstrated longer disease-free survival, a finding consistent with the "obesity paradox" described in the literature. These results highlight the need for further research into the complex role of body composition in HR+/HER2- breast cancer treated with CDK4/6 inhibitors. Citation Format: C. Pereira dos Santos, M. Celeleste Tavares, C. Campanholo Marques, S. Moraes Sanches. Impact of Body Mass Index on the Efficacy and Safety of Adjuvant Abemaciclib in a Real-World Brazilian Cohort of Patients With High-Risk Early Breast Cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-02-22.

Abstract Introduction: The incorporation of CDK4/6 inhibitors has significantly improved outcomes in patients with Luminal HER2-negative metastatic breast cancer. Nonetheless, resistance invariably emerges, limiting long-term efficacy and challenging subsequent treatment decisions. The therapy of choice after progression to cyclin inhibitor is not clearly defined, therefore molecular profiling may offer a valuable opportunity to uncover resistance mechanisms and identify actionable genomic alterations. This study aimed to characterize molecular alterations of luminal breast cancers treated with CDK4/6i in the real world setting, with the goal of guiding future therapy selection and optimizing treatment sequencing. Methods: Tumor samples were obtained from patients with HR+/HER2− breast cancer treated with CDK 4/6i, either from metastatic lesions collected at progression or from primary tumors prior to systemic therapy initiation. Following histopathologic evaluation and manual microdissection, DNA was extracted from FFPE tumor slides and sequenced using a targeted NGS panel (Somatic GS Focus Panel). The panel interrogates SNVs and Indels across 25 cancer-relevant genes (AKT1, ALK, ATM, BRAF, BRCA1, BRCA2, EGFR, ERBB2, ESR1, FGFR3, IDH1, IDH2, KIT, KRAS, MET, NRAS, PALB2, PDGFRA, PIK3CA, POLE, PTEN, RET, and TP53) and detects high-level copy number alterations in PTEN, EGFR and ERBB2. Variants were interpreted by molecular pathologists within a certified molecular diagnostics workflow. Results: Of the 72 patients selected, 16 (22%) were excluded due to insufficient DNA quality obtained from tumor samples or due to technical sequencing failure, resulting in 56 successfully sequenced cases. Among these, 30/56 (54%) presented a mutation in one of the genes analyzed. Pathway-level analysis revealed mutations in the PI3K/AKT/mTOR signaling in 21 (38%) cases (15 PIK3CA, 2 AKT1, 4 PTEN). Also related to resistance to endocrine therapy, ESR1 mutations were present in 3 tumors (5%). We also observed alterations related to homologous recombination deficiency in 5 cases (10%), including 1 BRCA1mut, 2 BRCA2mut, 2 ATMmut. Additionally, TP53 mutations were detected in 6 cases (8%) and ERBB2 mutations in 5 samples (7%). These genomic profiles reflect distinct therapeutic resistance mechanisms and highlight targetable vulnerabilities that may indicate the value of using agents like SERDs, PI3K inhibitors, or therapies targeting DNA repair deficiencies. Conclusion: Post-progression molecular profiling following CDK4/6 inhibitor failure reveals a diverse spectrum of clinically relevant alterations in luminal HER2-negative breast cancer. The predominance of PIK3CA, TP53 and ESR1 mutations, along with alterations in canonical signaling pathways, supports the integration of genomic data into post-CDK4/6 therapeutic planning. These findings reinforce the importance of a precision oncology approach to optimize treatment sequencing and personalize care for patients with HR+/HER2− metastatic breast cancer. The high failure rate (22%) of tissue testing underscores the need for more effective methods to obtain this valuable information, such as liquid biopsies. Citation Format: L. Coelho de Mattos, A. Cicilini, N. Soldi, V. Basilio, M. Godner, L. Leite, A. Ribeiro, R. Souza, N. Pandolfi, M. Tavares, F. Pinto, A. Diniz, M. de Brot, F. Makdissi, S. Sanches, V. Lima, E. Santana dos Santos. Rewiring Treatment Pathways: How Molecular Profiling After CDK4/6 Inhibitor (CDK4/6i) Failure Shapes Future Therapy in Luminal HER2-Negative Breast Cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-08-12.

<title>Abstract</title> Purpose Nutritional screening tools are widely used in routine oncologic care to identify patients at nutritional risk. However, their ability to identify hospitalized patients with relevant alterations in body composition remains unclear. This study aimed to evaluate whether nutritional screening tools routinely used in clinical practice capture patients with CT-defined changes in muscle mass and quality. Methods This retrospective, cross-sectional study included hospitalized adult cancer patients treated at a tertiary cancer center in São Paulo, Brazil, between 2022 and 2023. Eligible patients underwent abdominal computed tomography (CT) and nutritional screening during hospitalization. Skeletal Muscle Index (SMI) and skeletal muscle density (SMD) were assessed at the third lumbar vertebra (L3) using CoreSlicer® software. Nutritional risk was evaluated using routinely implemented screening tools, and associations with CT-derived body composition parameters were analyzed. Results 272 patients were included. Low muscle mass was identified in 51.1% of patients and low muscle density in 52.2%, including individuals with normal or elevated body mass index. Nutritional risk identified by NRS-2002 was significantly associated with SMI but showed limited ability to identify CT-defined alterations when used in isolation. The CNS demonstrated high sensitivity but low specificity. Many patients with CT-detected alterations in muscle mass and quality were not classified as at nutritional risk by screening tools. Conclusion Widely used screening instruments may overlook clinically relevant alterations in body composition among patients. When imaging is already available as part of routine oncologic care, opportunistic CT-based assessment may complement screening and support more individualized supportive care interventions