Romanian National Congress of Oncology, 2026

Double synchronous lung adenocarcinoma with discordant molecular profile:
a case report

C.Ș. Apetrei, Adela Văcar, A.B. Apetrei

Medical Oncology Clinical Department, Emergency County Clinical Hospital Târgu Mureș;
“George Emil Palade” University of Medicine, Pharmacy, Sciences and Technology,
Târgu Mureș, Romania

Corresponding author: A.B. Apetrei, e-mail: b_apetrei@yahoo.com

Objective. To highlight the diagnostic necessity and therapeutic challenge of sequencing targeted treatments in synchronous primary lung adenocarcinomas driven by divergent genomic alterations. Case presentation. A 76-year-old non-smoker female with cardiovascular comorbidities was diagnosed in March 2023 with two synchronous lung lesions: right lower lobe (RLL) and left upper lobe (LUL). Workup included CT/PET-CT, biopsy, histopathology, next-generation sequencing (NGS) and surgery. Results. The biopsy from the RLL tumor revealed an SDC4-ROS1 fusion. Targeted therapy with crizotinib led to a mixed response: the RLL tumor went into complete metabolic remission, but the LUL tumor continued to grow. Following a multidisciplinary tumor board discussion, the patient underwent surgery in January 2024 to remove the left upper lobe along with nearby lymph nodes (ypT2a N2 L0 Pn0 R0). After surgery, she completed two cycles of platinum-based chemotherapy (carboplatin plus pemetrexed). Genetic testing of the surgical tissue then identified an EGFR L858R mutation, proving that the two tumors were biologically independent primary cancers. She was then started on adjuvant osimertinib. In November 2024, the ROS1-positive cancer in the RLL returned, triggering a severe paraneoplastic condition with disseminated intravascular coagulation (DIC) and critically low platelet counts. Restarting crizotinib successfully controlled both the consumption coagulopathy and tumor burden until October 2025, when refractory bilateral pleural dissemination required thoracenteses, pleurostomy and an indwelling ASEPT catheter. Second-line nivolumab was initiated. The clinical course culminated in an acute ischemic stroke and refractory malignant cardiac tamponade, resulting in fatal multiorgan failure. Conclusions. This case underscores the necessity of independent molecular profiling for each synchronous neoplastic focus to guide rational, sequential tyrosine kinase inhibitor (TKI) therapy. Paraneoplastic vascular events and baseline cardiovascular fragility represent critical prognostic factors that can rapidly accelerate clinical deterioration.

Challenging boundaries: curative endoscopic submucosal dissection
for mixed-histology early gastric cancer – a pathologist’s perspective

Didina-Cătălina Barbălată^1,2, Andrei Voiosu^2,3,
Luciana Nichita^1,2, Cristiana Popp^1,2

1. Department of Pathology, Colentina Clinical Hospital, Bucharest, Romania

2. “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania

3. Department of Gastroenterology, Colentina Clinical Hospital, Bucharest, Romania

Objective. The study aims to highlight the curative potential of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) and to present the challenges faced by the pathologist in reaching a complete diagnosis. We report a case of ESD performed for a mixed-histology EGC, achieving a score of 0 on the endoscopic curability scale for undifferentiated carcinoma (eCuraU). Materials and method. A 53-year-old male patient underwent ESD for a 60/40 mm clinically diagnosed undifferentiated EGC located at the incisura angularis. The specimen, measuring 80/62/2 mm, was marked with clips corresponding to proximal (5 o’clock) and distal (8 o’clock) margins, pinned and fixed in formalin for 45 hours. To preserve orientation, the specimen was dyed with two inks, corresponding to upper and lower quadrants. The specimen was serially sectioned at 2 mm intervals, and the lateral margins were resected perpendicularly in order to determine the invasion. After processing, the specimen was microscopically analyzed for histological differentiation, ulceration, vertical and lateral invasion, lymphovascular and perineural invasion. Results. The specimen was resected in 31 sections. Microscopical analysis revealed a tumoral proliferation with signet ring cell morphology, invading focally the muscularis mucosae (maximum thickness 0.70 mm). Small foci of intestinal-type adenocarcinoma developed on high grade areas of dysplasia were identified. Margins were negative (0.23 mm from the deep margin, 20 mm from lateral margins), no lymphovascular invasion and no ulceration were identified. Based on these aspects, the eCuraU score was 0, corresponding to a low risk of lymph node metastasis. Endoscopic and imagistic workup at three months after resection were negative. Conclusions. This case showcases ESD as a minimally invasive, effective treatment option for undifferentiated EGC. The collaboration between endoscopist and pathologist in orientation and marking of the specimen facilitated an accurate diagnosis with precise analysis of invasion.

Complete radiological response
after definitive chemoradiotherapy
in unresectable tracheal spindle cell carcinoma: a case report

Valentina-Gabriela Bobilca¹, B.M. Chivu²

1. Radiotherapy Department, “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology,
Bucharest, Romania

2. Neolife Medical Center, Bucharest, Romania

Primary tracheal carcinomas are extremely rare malignancies, representing less than 0.2% of respiratory tract cancers. Spindle cell squamous cell carcinoma (SpC-SCC) is an uncommon and aggressive histological variant with major diagnostic challenges and limited therapeutic evidence. We report a rare case of unresectable distal tracheal SpC-SCC with carinal invasion treated with definitive concurrent chemoradiotherapy. A 73-year-old former heavy smoker (approximately 195 pack-years) with Global Initiative for Chronic Obstructive Lung Disease (GOLD) IV COPD, grade III hypertension, two previous ischemic strokes and prior carotid endarterectomy presented with one week of progressive dyspnea, cough and hemoptysis, becoming hypoxemic and tachypneic. Computed tomography (CT) showed an 18×16×28 mm mass of the posterior wall of the distal trachea extending to the carina and right main bronchus, without nodal or distant disease. Bronchoscopy confirmed a friable, necrotic tumor almost completely occluding the right main bronchus, and the respiratory reserve was severely limited, with a forced expiratory volume in 1 second (FEV1) of 23% predicted. Rigid-bronchoscopic debulking restored airway patency and secured the diagnosis of a poorly differentiated (G3) spindle cell squamous carcinoma, with Ki-67 of approximately 60% and loss of conventional epithelial markers. Programmed death-ligand 1 (PD-L1) expression was negative (tumor proportion score [TPS] <1%). The tumor was staged cT2 cN0 M0 according to the Piórek classification, which categorizes primary tracheal tumors based on their extent and local invasion. Carinal involvement and significant cardiopulmonary comorbidities made surgical resection unfeasible. Definitive image-guided intensity-modulated radiotherapy (IMRT) delivered 54 Gy in 27 fractions with a sequential boost to 66 Gy in 33 fractions, concurrent with weekly paclitaxel and carboplatin. The treatment was completed without interruption and with good tolerance. At the 12-month follow-up, the evaluation revealed complete radiological regression of the tracheal tumor, with no locoregional or distant progression. Spindle cell squamous cell carcinoma of the distal trachea and carina is an exceptionally rare entity, with limited therapeutic data. This case highlights the role of multidisciplinary management and demonstrates that definitive concurrent chemoradiotherapy with modern IMRT techniques can provide effective curative-intent treatment for unresectable tracheal carcinoma, even in patients with significant comorbidities.

Real-world experience with vismodegib
and cemiplimab in advanced basal
cell carcinoma: a single-center Romanian
case series

Cristina-Georgiana Bratu

“Dr. Carol Davila” Emergency University Central Military Hospital, Bucharest; “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania

Corresponding author: Cristina-Georgiana Bratu, e-mail: drcristinabratu@gmail.com

Introduction. Advanced basal cell carcinoma (aBCC) remains a therapeutic challenge in patients unsuitable for surgery or radiotherapy. Hedgehog pathway inhibitors (HHI) and anti-PD-1 immunotherapy have reshaped management, yet real-world data from Central and Eastern Europe remain scarce. Materials and methods. We retrospectively analyzed consecutive patients with locally advanced BCC treated in a single center with vismodegib 150 mg daily, with cemiplimab available upon progression or intolerance (December 2024 – September 2026). Treatment status, toxicity (CTCAE), dose modifications and best clinical response, assessed by a dermato-oncologist, were evaluated. Results. Nine patients were included (six males; median age: 67 years old; range: 52-85); two had Gorlin-Goltz syndrome. The predominant sites were periocular (n=3), multifocal scalp/facial disease (n=3) and the nasal pyramid (n=1); one patient had metatypical (basosquamous) carcinoma recurring on a free-flap reconstruction. Best response to vismodegib was partial response in 5/9 patients and stable disease in 3/9, corresponding to an objective response rate of 56% and disease control of 89%. Adverse events occurred in 6/9 patients: muscle spasms/arthralgia (n=6; grade 3 in one), dysgeusia (n=3), nausea (n=2) and alopecia (n=1). Toxicity was managed with alternate-day or intermittent dosing in 4/9 patients, allowing continued treatment; no discontinuation for toxicity occurred, and one patient stopped at his own request after grade 2 arthralgia. One patient progressed under vismodegib, with orbital and nasolacrimal duct invasion, and he was switched to cemiplimab, achieving a partial response. At data cutoff, 7/9 patients remained on vismodegib. Conclusions. In routine Romanian practice, vismodegib achieved meaningful disease control in locally advanced BCC with manageable toxicity; individualized intermittent dosing preserved treatment continuity, and cemiplimab proved a feasible option after HHI failure. Although vismodegib is not yet reimbursed in Romania and access remains challenging, this series offers a glimpse of real-world evidence from Romanian practice.

Don’t judge a tumor by its mucin:
one histology, two immune fates – MMR status resolves the hot-cold paradox
of mucinous colon adenocarcinoma

Ioana-Anastasia Cibotariu¹, Laura-Elena Stanciu¹,
Sabina Zurac^1,2, Alexandra Zeca¹, Cristiana Popp^1,2

1. Department of Pathology, Colentina Clinical Hospital, Bucharest, Romania

2. “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania

Introduction and objectives. Mucinous colon adenocarcinoma carries contradictory immunological reputations: mucin has been associated with reduced T-cell infiltration, predicting “cold” tumors, while mucinous morphology classically signals mismatch repair deficiency (MMRd) – the most immunogenic colorectal phenotype, predicting “hot” ones. We tested which prediction holds at the invasive margin by quantifying CD8-positive cell density in relation to mucinous differentiation and MMR expression. Materials and method. We retrospectively analyzed 35 patients (26 men, nine women; median age: 72 years old; range: 46-83) with confirmed colon adenocarcinoma. MMR proteins and CD8-positive cells were assessed immunohistochemically on the most representative invasive-margin blocks. CD8-positive cells were quantified digitally (QuPath v0.7.0) and dichotomized at an externally validated cut-off (231 cells/mm²). Mucinous differentiation was graded as absent, 1-50% or >50%. Results. Mucinous differentiation (18/35 tumors) was tightly linked to MMRd – 8/9 MMRd versus 10/26 MMRp tumors (p=0.018) – yet across the whole cohort mucin content predicted nothing: CD8-positive density did not differ by mucin category (p=0.446), grade, tumor budding or lymphovascular invasion (all p>0.4). Stratification by MMR status resolved this apparent silence: mucinous tumors split into the two immunological extremes of the cohort. MMRd mucinous carcinomas carried its densest infiltrates (median: 824.7 cells/mm²), while MMRp mucinous carcinomas were its most depleted subgroup (median: 170 cells/mm²; p<0.001), falling below the CD8-low cut-off. Within MMRp tumors, mucinous differentiation was directly associated with lower CD8-positive density than non-mucinous histology (170 versus 497 cells/mm²; p=0.008), concordant with large-cohort reports of mucin-associated T-cell depletion. Conclusions. One histology conceals two immune fates. In MMRd tumors, neoantigen-driven immunity dominates the phenotype regardless of mucin content; in MMRp tumors, mucin marks significantly lower CD8+ cell densities.

The importance of a multidisciplinary approach in the diagnosis and treatment of autoimmune toxicity

Simina Condruz

Oncology Department, MedLife Hospital Brașov, Romania

Small-cell lung cancer (SCLC) is a malignancy occurring almost exclusively in smokers, being associated with a poor prognosis and a high metastatic potential. Survival in patients with SCLC is lower than in those with other types of lung cancer. The addition of radiotherapy and immunotherapy has improved treatment outcomes in these tumors. We present the case of a 66-year-old former smoker diagnosed with small-cell lung cancer of the left inferior lobe. CT scan revealed locoregional lymphadenopathy and, also, raised the suspicion of an adrenal metastasis. Due to the extensive locoregional disease, treatment with chemoimmunotherapy was initiated, consisting of etoposide/carboplatin in combination with durvalumab. After two cycles of treatment, the patient developed severe dizziness. Brain metastases were ruled out by imaging, endocrine toxicity was excluded, and there was no evidence of cardiac toxicity. Following a comprehensive neurological evaluation, the patient was diagnosed with immune-mediated Guillain-Barré syndrome. She underwent four sessions of plasmapheresis, resulting in a gradual improvement in her neurological symptoms. Imaging reassessment demonstrated a partial response to oncological treatment. Continuation of treatment with concurrent chemoradiotherapy was planned. Subsequently, the patient developed fever, cough and dyspnea, being hospitalized with suspected pneumonia. Despite antibiotic therapy, her clinical condition deteriorated, with decreasing oxygen saturation, requiring transfer to the intensive care unit. Her condition gradually improved following corticosteroid therapy, and the episode was ultimately considered to represent immune-mediated pneumonitis. Chemoradiotherapy was subsequently continued, with favorable results. The patient achieved a complete pulmonary response; however, a pancreatic lesion was detected. At present, it cannot be definitively classified as either a primary pancreatic tumor or a secondary lesion related to the small-cell lung cancer. The patient is currently undergoing further gastroenterological evaluation.

Ribociclib in routine practice: hematological toxicity and dose management in the adjuvant versus metastatic setting – a single-center retrospective study

Angela-Maria Dincă¹, Elena Șerban¹, Laurenția-Nicole Galeș^1,2

1. Department of Medical Oncology II, “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest, Romania

2. “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania

Corresponding author: Angela-Maria Dincă, e-mail: angela.enache@drd.umfcd.ro

Objective. Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors are the standard of care in hormone receptor-positive, human epidermal growth factor receptor 2-negative (HER2-negative) breast cancer. Ribociclib is given at 600 mg/day in metastatic disease and 400 mg/day in the adjuvant setting. Neutropenia is the most frequent toxicity, and dose reduction is often used as its indirect marker. Materials and method. This is a retrospective, observational, single-center study of 46 women treated with ribociclib (21 adjuvant, 25 metastatic). Discharge summaries were reviewed and blood counts re-read individually in the laboratory system for 46 patients, graded per Common Terminology Criteria for Adverse Events (CTCAE) v5.0. We used Fisher’s exact and Mann-Whitney tests, two-sided =0.05. Results. Grade 3-4 neutropenia was confirmed in 3/46 patients (6.5%): 0/21 adjuvant and 3/25 metastatic (12%; p=0.24). Dose reduction for toxicity occurred exclusively in the metastatic arm: 6/25 (24%) versus 0/21 (0%), p=0.025. Only two of the six reductions were driven by neutropenia; the others followed renal failure, rash, cardiac deterioration and corrected QT interval (QTc) prolongation. Conversely, one grade-3 event required no reduction. Median treatment duration was 11.3 versus 21.8 months (p=0.009). Prior chemotherapy was more frequent in the adjuvant group (76.2% versus 36%; p=0.009). Conclusions. Dose reduction was significantly more frequent at 600 mg than at 400 mg, but it does not measure neutropenia: only one third of reductions were attributable to it. The observed grade 3-4 neutropenia rate (6.7%) is far below NATALEE (44.4%) and MONALEESA (60%) trials, a gap explained by when counts are drawn in routine care – on day 1 of the cycle, after the treatment-free week, not at nadir.

Tackling oligoprogression and endocrine toxicity in the age of immunotherapy:
a case of metastatic ccRCC

Diana-Elena Hosu-Durnea¹, Daniel-Vasile Dulf²

1. “Prof. Dr. Ion Chiricuță” Institute of Oncology, Cluj-Napoca, Romania

2. Municipal Clinical Hospital Cluj-Napoca, Romania

Corresponding author: Diana-Elena Hosu-Durnea, e-mail: dr.hosudiana@gmail.com

Introduction. Immune checkpoint inhibitors (ICIs) are the standard first-line treatment for metastatic clear cell renal cell carcinoma (ccRCC). However, discordant responses and oligoprogression create uncertainty regarding whether to maintain an effective systemic regimen and add metastasis-directed therapy (MDT), or to change systemic therapy. Additionally, endocrine immune-related adverse events (irAEs) are common and generally manageable with hormone replacement and do not necessarily require permanent ICI discontinuation. Case presentation. A 68-year-old male underwent partial nephrectomy in February 2024 for stage III ccRCC. In August 2024, he developed distant metastases (IMDC intermediate risk) and initiated first-line nivolumab plus ipilimumab, followed by nivolumab maintenance. Concurrently, he developed grade-3 hypothyroidism secondary to ICI. Nivolumab was temporarily withheld for steroid tapering and hormone replacement, then safely resumed upon clinical and biological normalization. In June 2025, CT showed a dissociated response: overall regression but progression of an infracarinal lymph node and a new right third-rib lesion. MDT with SBRT was delivered to the bone metastasis while nivolumab was continued. By November 2025, imaging confirmed the response at the irradiated rib and overall disease control. In March 2026, persistent pulmonary growth, a new right hilar node and two new hepatic metastases met iRECIST1.1 criteria for progressive disease. Nivolumab was discontinued, and second-line cabozantinib was initiated. At the first reassessment in June 2026, tumor burden decreased by 28%, with no new lesions. Conclusions. MDT with SBRT can prolong the clinical benefit from an effective ICI backbone in carefully selected oligoprogressive ccRCC. However, increasing multisite progression signals systemic resistance, prompting a switch to targeted therapy like cabozantinib. Proactive management of endocrine irAEs allows the safe continuation of ICIs, without compromising outcomes.

Biomarkers-driven systemic therapies
in advanced and metastatic breast cancer

Dan-Corneliu Jinga

Neolife Clinic, Bucharest; Faculty of Medicine, “Titu Maiorescu” University, Bucharest, Romania

Corresponding author: Dan-Corneliu Jinga, e-mail: dan.jinga@neolife.ro

Introduction. Comprehensive genomic profiling (CGP) increasingly guides therapy in advanced breast cancer, where alterations in the estrogen-receptor and PI3K/AKT/PTEN pathways inform endocrine, targeted and immunotherapeutic strategies. Tissue biopsy remains the reference standard, but it is limited by sample availability, quality and its capacity to capture spatial and temporal heterogeneity. Plasma-derived circulating tumor DNA (ctDNA) offers a minimally invasive, repeatable complement enabling real-time molecular characterization and resistance monitoring. Objective. To evaluate the analytical robustness and clinical utility of a hybrid capture-based 1021-gene next-generation sequencing (NGS) assay (Oncology Multi-Gene Variant Assay, GenePlus) applied in parallel to formalin-fixed paraffin-embedded (FFPE) tissue and plasma, emphasizing the incremental diagnostic yield of integrated tissue-and-plasma profiling in breast cancer. Materials and method. The assay was validated analytically and clinically for single-nucleotide variants, insertions/deletions, copy-number variations and gene fusions, as well as microsatellite instability (MSI) and tumor mutational burden (TMB), down to a 0.5% variant allele frequency with 100% positive and negative percent agreement on reference standards (Meintani et al., International Journal of Molecular Sciences, 2025). Real-world metastatic implementation incorporated parallel leukocyte sequencing to exclude clonal hematopoiesis and identify germline variants (Florou-Chatzigiannidou et al., Scientific Reports, 2026). Concordance between matched FFPE and plasma specimens was assessed for on-label, off-label and resistance-associated alterations. Results. Breast cancer showed the highest proportion of on-label biomarkers of any tumor type (44.13% of cases in the liquid-biopsy cohort), driven predominantly by PIK3CA mutations, ESR1 alterations and ERBB2 amplification, with ESR1 alterations recurring as endocrine-therapy resistance events (Florou-Chatzigiannidou et al., Scientific Reports, 2026). PIK3CA was the most frequent on-label gene overall (40 patients), followed by ESR1 (28 patients). In paired-specimen analysis, concordance for clinically actionable on-label variants between tissue and plasma reached approximately 90%, confirming ctDNA reliability for truncal, high-allele-fraction targets, while certain resistance-associated and subclonal alterations (e.g., ESR1) were detected uniquely in plasma. Parallel white-blood-cell sequencing enabled confident germline detection (11.26% of patients overall, including BRCA1/2 carriers) and mitigated clonal-hematopoiesis-driven false positives. Conclusions. Integrated next-generation sequencing of matched tumor tissue and plasma affords a robust, clinically actionable platform for precision oncology in breast cancer, wherein the two modalities act synergistically to enhance the detection of actionable alterations, longitudinal surveillance of resistance and the evaluation of immunotherapy biomarkers.

Two decades on TKI: an exceptional
long-term survivor of metastatic RCC
and the current treatment landscape

Dan-Corneliu Jinga¹, Polixenia Iorga², Irina Anghel¹,
Raluca Bulboacă¹, Valentina Bobilca³, Bogdan Chivu³

1. Department of Medical Oncology, Neolife Medical Center, Bucharest; Faculty of Medicine, “Titu Maiorescu” University, Bucharest, Romania

2. Department of Medical Oncology, Emergency University Hospital Bucharest;
Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania

3. Department of Radiotherapy, Neolife Medical Center, Bucharest, Romania

Introduction. Before the targeted-therapy era, metastatic renal cell carcinoma (mRCC) had a poor prognosis. The introduction of vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs), including sorafenib and sunitinib, substantially improved the outcomes, and their limited cross-resistance supported sequential use. Case presentation. We report a patient with chromophobe renal cell carcinoma (chRCC) who has survived for more than 20 years with metastatic disease, including prolonged disease control with sequential sorafenib followed by sunitinib. The patient, a 35-year-old man with a solitary horseshoe kidney, was diagnosed in November 2005 with metastatic non-clear cell RCC by peritoneal biopsy, although the primary renal tumour was not initially identified. After two lines of therapy (immunotherapy and chemotherapy), progressive mediastinal and abdominal lymphadenopathy developed. Sorafenib was initiated in December 2007, achieving disease control for almost five years. In September 2013, local and regional disease was surgically resected, including complete nephrectomy. Sunitinib was started in October 2013 for persistent metastatic mediastinal lymph nodes and has maintained long-term disease control. The patient has remained on sunitinib, with stable mediastinal and abdominal lymph node disease, and on chronic dialysis since 2013 with a good performance status. He was among the earliest Romanian patients with RCC treated with a TKI. Conclusions. This exceptional clinical course illustrates that prolonged disease control may be achieved with sequential VEGFR-TKI therapy in selected patients with favourable tumor biology. Although current first-line treatment of mRCC is dominated by immune checkpoint inhibitor-based combinations, TKIs still kept a role in individualized treatment strategies. Identifying clinical and molecular predictors of exceptional long-term response remains an important research priority.

Adjuvant radiotherapy in patients
with implant-based breast reconstruction – Albanian experience

Erald Karaulli, Helidon Nina, Bledi Kreka, Fatjona Kraja

UHCT “Mother Teresa” Oncology Service, Tirana, Albania

Introduction. Radiotherapy is a crucial component of breast cancer treatment, particularly for node-positive, locally advanced and large tumors, often delivered post-mastectomy (PMRT). However, radiotherapy can negatively impact breast reconstruction outcomes, leading to complications like poor cosmesis, infections and reconstruction failure. While advancements in targeted radiotherapy and reconstruction techniques have reduced these issues, challenges remain, particularly concerning the timing and type of reconstruction to optimize both cosmetic and oncologic outcomes. In recent years, in Albania, the number of patients with breast implants treated with radiotherapy has increased. Materials and method. We retrospectively evaluated 23 patients with breast implants who received adjuvant radiotherapy between 2021 and 2025. Breast reconstruction was performed at our public hospital, in private clinics in Albania, or abroad. Patient demographics, reconstructive technique, implant position, type of breast prosthesis and radiotherapy-related complications were assessed. Both definitive implant-based reconstruction and two-stage reconstruction using tissue expanders were included. All patients were treated using volumetric modulated arc therapy (VMAT). The primary focus of the study was the occurrence of treatment-related complications following radiotherapy. Results. The mean age of the patients was 39.4 years old. Fourteen patients (61%) underwent definitive pre-pectoral implant-based breast reconstruction, while two patients (9%) had subpectoral implants. Tissue expanders were used in seven patients (30%) as part of a two-stage reconstructive approach. Following radiotherapy, capsular contracture and implant failure were observed in two patients. Conclusions. Implant-based breast reconstruction remains a feasible option for patients requiring adjuvant radiotherapy. Patients should be counseled regarding the risks of capsular fibrosis, contracture and implant failure. The decision regarding one- or two-stage reconstruction should be individualized and discussed within a multidisciplinary breast tumor board. Further patient accrual and longer follow-up are needed to better define long-term outcomes in our population.

Gastric cancer in Albanian university
clinical practice – treatment modalities
and relapse-free survival of gastric cancer

Bledi Kreka, Ervin Toci, Helidon Nina, Dea Kreka, Erald Karaulli, Fatjona Kraja, Manika Face-Kreka, Arvin Dibra

UHCT “Mother Teresa” Oncology Service, Tirana, Albania

Introduction. In Eastern Europe, where late cancer diagnoses are frequent and survival rates are low, gastric cancer continues to be a leading cause of cancer-related death. Information about the real-world management of gastric cancer in Albania is still limited. Materials and method. This was a prospective longitudinal observational study including 221 patients treated during a four-year period in UHCT “Mother Teresa” Oncology Service, Tirana, Albania. This study aimed to describe the clinic pathological profile, treatment patterns of gastric and relapse-free survival interval of localized stage patients treated in our oncology center. Results. The mean age of the patients was 64±9.9 years old, and most of them were men (71.5%). The diffuse histological type was found in 49.1% of cases, while the intestinal type accounted for 47.7%. A large proportion of patients were diagnosed in advanced stages of disease, with 85.9% classified as T3-T4 tumors. Regional lymph node involvement was present in 78.7% of the patients, and distant metastases were identified in 19.9% at the diagnosis. Surgical treatment was performed in most patients (82%). Adjuvant therapy was used in 69.5% of cases, whereas neoadjuvant treatment was used only rarely (3.2%). Radiotherapy and curative chemotherapy were administered in 14.5% and 12.2% of patients, respectively. Relapses occurred in 37.1% of patients during follow-up. The median relapse-free survival was 28 months (95% CI; 25.04-30.96). The relapse risk strongly correlated with increasing lymph node involvement (N1: HR=5.31; N2: HR=6.53; N3: HR=9.59). Conclusions. Most gastric cancer patients in Albania continue to present with advanced disease. The management is still based mainly on surgery followed by postoperative treatment. The low use of neoadjuvant therapy may suggest difficulties in the implementation of modern multimodal treatment strategies in everyday clinical practice.

Palliative radiotherapy in advanced head and neck cancer: meta-analysis across hypofractionation schedules

Horia-Dan Lișcu^1,2, Lucian-Ionuț Antone-Iordache^1,3,
Georgiana Gagiu^1,3, Iman Mologani^1,3

1. “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania

2. Radiotherapy Department, Emergency University Hospital Bucharest, Romania

3. Radiotherapy Department, Colțea Clinical Hospital, Bucharest, Romania

Corresponding author: Horia-Dan Lișcu, e-mail: horia.liscu@umfcd.ro

Introduction and objective. Once cure is no longer achievable, short-course radiotherapy remains the main local option in advanced head and neck cancer. Practice is heterogeneous: many fractionation schemes are in use, and none has emerged as standard. Quad Shot carries the largest body of evidence among them, yet it has seldom been placed side by side with competing short-course schedules in a quantitative synthesis. We therefore pooled the available data to test whether outcomes differ between Quad Shot and other hypofractionated palliative approaches. Materials and method. Three databases (MEDLINE, Scopus, Web of Science) were queried for reports issued between January 2005 and December 2025, following PRISMA 2020. Study quality was appraised with the NIH Quality Assessment Tools. Included cohorts were assigned to one of two groups: Quad Shot or other hypofractionated schedules. Random-effects models generated pooled figures for overall response rate (ORR), median overall survival (OS) and grade-3 mucositis and dermatitis. Results. Fifty reports contributed with 3671 patients. Median OS was similar in the two groups, with most cohorts reporting between 6 and 10 months. Response was likewise near-identical (ORR 0.66 versus 0.67; p=0.91). Severe dermatitis was infrequent in both groups, and the small difference favoring Quad Shot was not statistically significant. Grade-3 mucositis appeared less frequently under Quad Shot (1% versus 10%; p=0.002), an association that withstood adjustment for delivery technique and BED10, but dissolved once outlying cohorts were removed, showing the estimate rests on few studies. Seventy percent of patients received all three planned cycles. Conclusions. Quad Shot performs on a par with competing hypofractionated schedules in both disease response and treatment burden, and it remains a defensible palliative option in advanced head and neck cancer. The apparent mucositis advantage is not robust and awaits prospective confirmation.

Histologic transformation to small-cell lung cancer as a mechanism of relapse
on adjuvant osimertinib in EGFR-mutant lung adenocarcinoma: diagnostic
and therapeutic challenges

Ana-Maria Matei, Mădălina Tolea, Andreea Pătrașcu

Department of Medical Oncology, “Elias” Emergency University Hospital, Bucharest;
“Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania

Corresponding author: Ana-Maria Matei, e-mail: anamaria2001matei@gmail.com

Introduction. Adjuvant osimertinib is the standard of care for resected EGFR-mutated non-small cell lung cancer. While histologic transformation to small-cell lung cancer (SCLC) is a recognized mechanism of acquired resistance in metastatic disease (3-10%), its emergence in the adjuvant setting remains rare and poses significant clinical challenges. Case presentation. A 63-year-old female underwent left lower lobectomy and lymphadenectomy in September 2023 for pT2aN2 lung adenocarcinoma harboring an EGFR exon 21 L858R mutation. Following adjuvant cisplatin-pemetrexed, adjuvant osimertinib was initiated in January 2024. In May 2026 (after 28 months of therapy), surveillance CT revealed aggressive intrathoracic progression with necrotizing mediastino-hilar adenopathies and pulmonary nodules. Repeat thoracoscopic biopsy confirmed small-cell neuroendocrine carcinoma. Comprehensive tissue NGS revealed persistence of the original EGFR L858R mutation (VAF 38%), along with a TP53 mutation and MYCL amplification. The patient was started on carboplatin, etoposide and durvalumab, with thoracic consolidative radiotherapy planned for multidisciplinary evaluation. Discussion. This case highlights the imperative role of repeat tissue biopsy upon progression on tyrosine kinase inhibitors (TKIs), as liquid biopsy cannot identify phenotypic transformation. The identified genomic alterations (TP53, MYCL) represent characteristic features of neuroendocrine divergence. The clinical management raised key debates: the addition of durvalumab per standard SCLC regimens despite limited evidence for immunotherapy in EGFR-driven disease, safety considerations regarding subsequent TKI re-challenge, and the value of local consolidation with radiotherapy in thorax-confined relapse. Conclusions. SCLC transformation is an aggressive pathway of relapse under adjuvant osimertinib. Prompt tissue re-biopsy and comprehensive molecular testing are vital to shift therapy toward small-cell regimens and optimize subsequent treatment sequences.

Personalized medicine in metastatic
HR-positive breast cancer: cerebrospinal fluid genomic profiling guiding treatment decisions in leptomeningeal disease

Radu Matei^1,2, Adelina-Silvana Gheorghe¹,
Anca-Alexandra Stolojanu¹, Elena Iovănescu^1,2, Ioana Geală¹, Ioana Dochinoiu¹, Sânziana Prundianu¹,
Dana-Lucia Stănculeanu^1,2

1. “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest, Romania

2. “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania

Corresponding author: Radu Matei, e-mail: radu.matei@drd.umfcd.ro

Introduction. The treatment landscape of hormone receptor (HR)-positive metastatic breast cancer has evolved beyond CDK4/6 inhibitors with the integration of targeted therapies and antibody-drug conjugates. Despite these advances, atypical patterns of progression and diagnostic uncertainty underscore the limitations of standard approaches and support the need for individualized treatment strategies. Case presentation. We report the case of a 47-year-old female diagnosed with stage IV invasive lobular breast carcinoma, HR-positive, HER2-low, with extensive bone, nodal and bone marrow involvement at diagnosis. Severe thrombocytopenia prompted the initiation of chemotherapy as first-line treatment. Endocrine therapy combined with a CDK4/6 inhibitor was subsequently introduced; however, disease progression shortly appeared. Given the HER2-low expression, trastuzumab deruxtecan was initiated, achieving a partial radiological response and good tolerability. During follow-up, the patient developed neurological symptoms with a fluctuating course. Serial brain MRI evaluations remained inconclusive, raising suspicion of leptomeningeal involvement without definitive confirmation. Initial cerebrospinal fluid (CSF) cytology was non-diagnostic. Further work-up included CSF analysis and liquid biopsy. While plasma circulating tumor DNA was undetectable, CSF-based next-generation sequencing demonstrated a high tumor fraction and revealed a tumor mutational burden higher than 10 mut/Mb (TMB-high). Based on TMB-high status, pembrolizumab was initiated, with improvement in neurological symptoms and good tolerability. Conclusions. This case emphasizes the value of molecular profiling in individualizing treatment decisions. In selected scenarios, site-specific genomics can reveal actionable biology beyond standard approaches, highlighting how precision medicine can meaningfully influence patient outcomes.

Sinonasal mucosal melanoma
with local recurrence despite adjuvant pembrolizumab: salvage radiotherapy and nivolumab-ipilimumab combination therapy – a case report

I.C. Mihai, T.C. Berisha, A.M. Ciurea, A.M. Mehedințeanu,
E.C. Nuță, L. Bițână

“Sf. Nectarie” Oncology Center, Craiova; University of Medicine and Pharmacy of Craiova, Romania

Objective. To report a case of sinonasal mucosal melanoma with repeated local recurrence despite radical surgery and adjuvant anti-PD-1 monotherapy, illustrating the therapeutic sequence that included salvage radiotherapy and combination immune checkpoint blockade. Materials and method. We present the case of a 66-year-old woman diagnosed with BRAF-negative malignant melanoma of the right nasal fossa. The initial treatment consisted of radical excision of the right maxillary sinus with polypectomy (March 2025), with histopathology confirming acral/amelanotic melanoma, pT3. A second intervention (October 2025), comprising polypectomy, inferior and middle uncinectomy, radical maxillary sinus clearance, ethmoidectomy and antrostomy, was followed by adjuvant pembrolizumab, administered for eight cycles. Despite adjuvant immunotherapy, local disease progression occurred, requiring two further excisions (January and May 2026) for recurrent tumor in the nasal fossa and the naso-sino-orbital region, both confirmed as melanoma. Given the persistent local evolution, the patient subsequently received radiotherapy (70 Gy; June-August 2026) followed by the initiation of combination immunotherapy with nivolumab and ipilimumab. Results. The disease course, spanning four surgical interventions and adjuvant anti-PD-1 monotherapy, illustrates the markedly recurrent local behavior of sinonasal mucosal melanoma despite guideline-concordant adjuvant treatment. The patient is currently undergoing salvage radiotherapy and combination nivolumab-ipilimumab therapy, with close multidisciplinary follow-up (ENT, ophthalmology) and periodic imaging planned to assess the response and to detect further recurrence or toxicity. Conclusions. Sinonasal mucosal melanoma is a rare, biologically aggressive subtype with a strong tendency toward local recurrence, even after radical surgery and adjuvant anti-PD-1 therapy. This case highlights the value of salvage radiotherapy and dual immune checkpoint blockade (nivolumab plus ipilimumab) as a therapeutic option in patients who progress on anti-PD-1 monotherapy, together with structured multidisciplinary surveillance.

Beyond biomarkers: perioperative immunotherapy in gastric cancer

I.A. Mirea, Ioana-Niculina Luca, Adina-Emilia Croitoru

Department of Medical Oncology, Fundeni Clinical Institute, Bucharest, Romania

Introduction. The perioperative treatment of resectable gastric adenocarcinoma is continuously evolving. Results from the phase III MATTERHORN trial demonstrated a benefit from adding durvalumab to FLOT chemotherapy, with improved event-free survival and pathological response. Case presentation. We present the case of a 41-year-old woman with persistent gastrointestinal symptoms, in whom the investigations revealed an infiltrative gastric lesion. Histopathological examination confirmed a diffuse-type, poorly cohesive, poorly differentiated G3 gastric adenocarcinoma with mucinous features and focal signet-ring cells. PET-CT revealed gastric wall thickening and regional lymphadenopathy, with no distant metastases. The biological profile was MSS, HER2-negative, claudin 18.2-negative and PD-L1 CPS 0. Given the localized disease and the availability of an early-access program at our institution, perioperative treatment with FLOT plus durvalumab was initiated. Four neoadjuvant cycles were administered, with good tolerance, followed by total gastrectomy with lymphadenectomy. Histopathological examination showed diffuse-type G3 gastric adenocarcinoma, ypT3N1, with 2/40 positive lymph nodes, lymphovascular and perineural invasion, with negative resection margins and a partial treatment response (TRG 2). Perioperative treatment was continued with FLOT plus durvalumab, followed by durvalumab monotherapy. At the latest assessment, the patient had an ECOG performance status of 1, being in good general condition, and had no clinical evidence of disease recurrence. Conclusions. This case illustrates the use of perioperative FLOT plus durvalumab in a patient with localized gastric adenocarcinoma, unfavorable biological features, and no conventional predictive biomarkers. Early access to this treatment strategy allowed the implementation of recent MATTERHORN data in clinical practice, with a partial pathological response and a favorable clinical course.

Treating the untreatable?
A multidisciplinary therapeutic journey in advanced hepatic epithelioid hemangioendothelioma

Ioana Chiriac-Moruzzi, Dragoș-Petru-Teodor Iancu

Regional Institute of Oncology Iași, Romania

Introduction and objective. Hepatic epithelioid hemangioendothelioma (HEHE) is a rare vascular malignancy with an unpredictable clinical course and limited evidence on systemic treatment. In advanced disease, treatment decisions are challenging and often require an individualized, multidisciplinary approach. We present the clinical course of a young patient with advanced HEHE, focusing on the sequence of systemic, local and supportive treatments. Case presentation. A 34-year-old woman was diagnosed with stage IV hepatic HEHE with TFE3 gene rearrangement. The diagnosis was established by multiphasic CT, MRI, core-needle biopsy and immunohistochemistry. Histology showed epithelioid morphology with positivity for CD31, CD34 and ERG. The patient underwent orthotopic liver transplantation (OLT) in January 2023 and received sirolimus-based immunosuppression. In May 2023, biopsy confirmed acute/chronic graft rejection, followed by progressive extrahepatic disease. Subsequent CT, MRI and PET/CT revealed bilateral pulmonary micronodules with ground-glass opacities and extensive osteolytic metastases involving the thoracic and lumbar spine, sacroiliac joints and pelvis. With progressive metastatic disease, treatment options were discussed within a multidisciplinary team. The patient subsequently entered the phase I TEADES clinical trial and received the investigational oral pan-TEAD inhibitor ODM-212. Bisphosphonates were also administered because of extensive bone involvement. Increasing cancer-related bone pain led to palliative radiotherapy. The thoracic and lumbar spine were treated with a planned dose of 30 Gy in ten fractions, followed by planned irradiation of the sacropelvic lesions with 16 Gy in four fractions. Radiotherapy was subsequently interrupted during therapeutic reassessment, in the setting of newly documented pulmonary abnormalities and the need for a treatment-free interval before consideration of pazopanib. Molecular/genetic testing was also performed to help guide further treatment decisions. Results. Radiotherapy resulted in a significant improvement of cancer-related bone pain, without major acute radiation-related toxicity. Despite the different therapeutic approaches, pulmonary and skeletal metastatic disease persisted, requiring continued systemic and supportive treatment. Conclusions. This case illustrates the difficulty of treating advanced hepatic epithelioid hemangioendothelioma in the absence of a standardized systemic treatment strategy. Treatment required repeated reassessment and adjustment according to disease progression, symptoms and available therapeutic options. A multidisciplinary approach combining systemic and investigational treatment with bone-directed therapy and palliative radiotherapy was essential throughout the course of the disease.

Metastatic gastric adenocarcinoma claudin 18.2 positive

Cornelia Nițipir, Cristina-Maria Orlov-Slavu, Ioana Cocona

Department of Medical Oncology, “Prof. Dr. Agrippa Ionescu” Clinical Emergency Hospital, Balotești, Romania

This case highlights the clinical value of biomarker profiling in metastatic gastric adenocarcinoma, the efficacy and tolerability of zolbetuximab combined with mFOLFOX6 in a CLDN18.2-positive, HER2-negative tumor. Relevant diagnostic, pathological, molecular, imaging and treatment data from the medical records of a 70-year-old woman with gastric adenocarcinoma were retrospectively reviewed. Endoscopy identified a large ulcerated lesion at the gastric angle. Histopathology confirmed poorly differentiated G3 gastric adenocarcinoma. Staging PET-CT demonstrated an FDG-avid gastric primary tumor, perigastric lymphadenopathy and metabolically active peritoneal nodules, consistent with stage IV disease with peritoneal metastases. Tumor profiling showed CK7 and CEA positivity, Ki-67 90%, HER2 negativity, discordant PD-L1 CPS results (CPS1 with 22C3) and CLDN18.2 positivity in 90% of tumor cells. DPD status was wild-type. After final diagnosis and staging, mFOLFOX6 was initiated. 5-FU was initially administered at 50% of the planned dose, while DPD testing was pending, then continued at full dose. Zolbetuximab was added in accordance with biomarker-directed treatment for HER2-negative, CLDN18.2-positive, metastatic gastric cancer. A favorable treatment response was observed, with tumor markers (CEA and CA 19-9) decreasing significantly during treatment. Response assessment PET-CT revealed the disappearance of previously metabolically active subdiaphragmatic lymphadenopathy and no detectable peritoneal nodules or ascites, while the primary gastric tumor was still active. Toxicities included grade I peripheral neuropathy, grade II nausea and vomiting during zolbetuximab infusion, prompting a reduction in the infusion rate to 40 mL/h, after which the treatment was well tolerated, with weight loss and hypoalbuminemia, raising the possibility of zolbetuximab induced gastritis. Therefore, biomarker-driven treatment selection was associated with favorable oncologic outcomes and manageable toxicity in a metastatic gastric cancer.

Interactions between intratumoral microbiota and immune cell infiltration
in colorectal cancer

M. Novac¹, V. Țuțuianu¹, Valentina Stratan¹, Cristina Popa¹,
Galina Coltuclu¹, Diana Andrușca¹, Veronica Balan¹, M. Ciobanu², N. Balan², L. Bejenaru²

1. Scientific Laboratory of Cancer Biology, IMSP Institute of Oncology, Chișinău, Republic
of Moldova

2. Proctology Department, IMSP Institute of Oncology, Chișinău, Republic of Moldova

Introduction and objective. Colorectal cancer (CRC) progression is influenced by microbial dysbiosis and immune modulation. This study, conducted between January 2024 and May 2026, aimed to evaluate correlations between intratumoral microbial signatures and immune cell profiles, focusing on CD4/CD8 balance and cytotoxic T-cell infiltration. Materials and method. Tumor and adjacent normal tissue (NAT) samples were collected intraoperatively from 15 patients with CRC staged M0 and T2-T3 lesions undergoing curative surgery, being processed under aseptic conditions. Microbiome profiling was performed using 16S rRNA sequencing. Immune parameters were assessed by multiparametric flow cytometry using a panel of CD3, CD4, CD8, CD14, CD20, CD45 and CD45RO. Statistical and bioinformatic analysis was performed using R language. Results. Microbial composition differed significantly between tumor and NAT (p=0.001). Tumors showed enrichment of oral anaerobes (Campylobacter, Treponema, Selenomonas) and depletion of SCFA-producing commensals (Faecalibacterium, Blautia). Eggerthella and Bacteroides correlated positively with CD8+ T cells, while Prevotella aligned with CD4+ T cells and elevated CD4/CD8 ratio. Collinsella was strongly associated with NK cells, while Parabacteroides and Ruminococcus with B cells. Canonical correspondence analysis (CCA) revealed CD8+ infiltration as the main ecological gradient, clustering with Shigella and Pyramidobacter. Additional clustering patterns highlighted antagonistic relationships between CD4+ and CD8+ immune axes, confirming distinct microbial-immune modules within the tumor microenvironment. Discussion and conclusions. Intratumoral dysbiosis in CRC is aligned with specific immunological deviations. The data suggest that microbial communities contribute to shaping distinct immune axes, with cytotoxic (CD8+) and helper (CD4+) responses structured by different bacterial taxa. The observed segregation of taxa into functional modules underscores the role of microbiome composition in defining immune architecture, supporting the concept of a microbially driven remodeling of the tumor microenvironment.

Atezolizumab-bevacizumab beyond IMbrave150 eligibility: outcomes
in advanced hepatocellular carcinoma with baseline platelet counts below 75,000/μL

Denisa Oprean, R.A. Vidra

Medical Oncology Department, “Prof. Dr. Octavian Fodor” Regional Institute of Gastroenterology and Hepatology, Cluj-Napoca, Romania

Corresponding author: Denisa Oprean, e-mail: opreandenisa2@gmail.com

Introduction. Patients with advanced hepatocellular carcinoma and baseline platelet counts below 75,000/μL were excluded from the pivotal IMbrave150 trial, leaving limited evidence to guide treatment decisions in this high-risk population. We evaluated the safety and clinical outcomes of first-line atezolizumab plus bevacizumab in patients with thrombocytopenia below this threshold. Materials and method. We conducted a retrospective case series including nine patients with advanced hepatocellular carcinoma treated with first-line atezolizumab plus bevacizumab at our institution. All patients had baseline platelet counts below 75,000/μL. Clinical characteristics, liver function, portal hypertension status, variceal prophylaxis, treatment exposure, tumor response and bleeding events were collected from medical records. Results. Median age was 65 years old (range: 24-74), and 77.8% were males. Cirrhosis, portal hypertension and esophageal varices were present in 88.9% of patients. Child-Pugh class was A in 66.7%, B in 22.2% and C in 11.1%. BCLC stage B and C disease accounted for 55.6% and 44.4% of cases. Baseline platelet counts ranged from 44,000 to 71,000/μL, and the median number of treatment cycles was 5 (3-15). Among six evaluable patients, four (66.7%) achieved stable disease, while two (33.3%) had primary progressive disease. Three patients were non-evaluable due to early discontinuation or loss to follow-up. During treatment, one patient (11.1%) developed upper gastrointestinal bleeding, attributed to probable variceal rupture after the fifth cycle, leading to treatment discontinuation. No other hemorrhagic events were recorded despite low platelet counts in several patients throughout therapy. Conclusions. In this real-world series, atezolizumab plus bevacizumab were feasible in selected patients with baseline thrombocytopenia below 75,000/μL. Bleeding complications were uncommon, with only one variceal hemorrhage observed, suggesting that thrombocytopenia alone should not necessarily represent an absolute contraindication when patients undergo appropriate assessment and management of portal hypertension and esophageal varices.

Stereotactic radiotherapy
as a treatment-line-sparing strategy
in oligoprogressive solid tumors:
time to next systemic therapy

Dan-Dumitru Pop, Tatiana Cirimpei, Cristina Coza

Radiotherapy Department, Medisprof Cancer Center, Cluj-Napoca, Romania

Corresponding author: Dan-Dumitru Pop, e-mail: danpop@medisprof.ro

Objective. To evaluate whether stereotactic body radiotherapy/stereotactic radiosurgery (SBRT/SRS) for oligoprogressive solid tumors can prolong the continuation of an otherwise effective systemic treatment line. Materials and method. We retrospectively analyzed 101 unique patients with oligoprogressive solid tumors treated with SBRT/SRS while receiving active systemic therapy. The primary endpoint was time to next systemic therapy (TTNT), measured from SBRT/SRS to progression-triggered initiation of the next systemic line; patients without a treatment change were censored at death or at the data-lock date (1 May 2026), as applicable. Progression-free survival (PFS) was operationally defined from SBRT/SRS to progression-triggered treatment change or death. Overall survival (OS) was calculated from SBRT/SRS to death. Local control and best radiological response were evaluated per irradiated lesion. Kaplan-Meier estimates, log-rank tests and exploratory Cox regression were used. Results. Median TTNT was 11 months (95% CI; 7.5-15.3; 66 events). Median operational PFS was 10.5 months (95% CI; 7-14.9; 70 events) and median OS was 51.4 months (95% CI; 44.4-69.3; 25 deaths). Among 151 evaluable irradiated lesions, the objective response rate was 57%, while the disease control rate was 92.7%. Kaplan-Meier local control was 83.6% at six months and 69.5% at 12 months; median local control was not reached. In exploratory multivariable analysis, each additional irradiated lesion was associated with shorter TTNT (hazard ratio 1.37; 95% CI; 1.03-1.83; p=0.032), while the global model was borderline (p=0.054). Conclusions. SBRT/SRS for oligoprogression was associated with a median continuation of the same systemic treatment line of approximately 11 months. These findings support the prospective validation of treatment-line-sparing strategies and of lesion burden as a potential selection factor.

Real-world analysis of current
pathology practice of HER2 testing
in breast cancer in Romania (SPECTRUM):
challenges and implications

Ovidiu Pop^1,2, Alis-Liliana-Carmen Dema³, Dan Ferariu⁴,
Mihai Stoicea⁵, Corina Voinea⁶, Maria Olinca^7,8

1. University of Oradea, Romania

2. Resident Laboratory, Oradea, Romania

3. “Victor Babeș” University of Medicine and Pharmacy, Timișoara, Romania

4. Regional Institute of Oncology Iași, Romania

5. Unirea Medical Center – Regina Maria, Bucharest, Romania

6. Medical Department, AstraZeneca, Bucharest, Romania

7. Oncoteam Diagnostic, Bucharest, Romania

8. “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania

Introduction and objective. The current practice of human epidermal growth factor receptor 2 (HER2) testing by immunohistochemistry (IHC) in patients with breast carcinoma (BC) across Romanian pathology laboratories is scarcely documented. The real-world study SPECTRUM explored national patterns in HER2 IHC practices over two phases (2023 and 2024) to identify progress and challenges. Materials and method. This retrospective chart review was conducted by pathologists from public and private pathology laboratories. Information on each laboratory practice and the results of the HER2 IHC testing on formalin-fixed paraffin-embedded tissue over same three-month predefined periods, in 2023 and 2024, was extracted. The statistics were descriptive. Results. IHC testing practice in 2023 versus 2024: 22 versus 23 laboratories participated, 320 versus 350 median number of BC cases/year, 20 versus 25 median number of IHC HER2 tests/month, 77% versus 83% reflex HER2 IHC, 68% versus 70% reflex in situ hybridization (ISH) only on cases with IHC=2+ score. The most frequently used clone was pre-diluted VENTANA anti-HER2/new (4B5): 64% versus 57%. Standardized pathology reporting format was implemented in 68% of laboratories in 2023 compared to 56% in 2024. Detection kit was explored only in 2024 (52% ultraView). Participation in quality assurance programs was reported by 68% laboratories in 2023 and 78% in 2024. HER2 testing included 151 patients in the 2023 cohort and 161 in the 2024 cohort, with no differences between cohorts. Sensitivity analyses revealed that the probability for accurately classifying as HER2-low increased in 2024 (p=0.074 by Fisher’s exact test, confirmed by multilevel logit models; OR=2.28; p<0.10). Conclusions. Modest improvements over one-year period were noted in HER2 testing practice. External control is in place in most sites, yet variability in reporting and methodology remains a challenge. Expanding standardization efforts is crucial, as accurate HER2 assessment underpins the identification of patients eligible for emerging targeted therapies in breast carcinoma.

Funding: AstraZeneca

Therapeutic challenges in synchronous colorectal and pancreatic malignancies in a patient with Bloom syndrome phenotype and compound heterozygous BLM variants

Danușia Pușcașu, Elena Șerban, Laurenția Galeș

Department of Medical Oncology, “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest, Romania

Introduction. Bloom syndrome is a rare autosomal recessive disorder characterized by genomic instability, distinctive phenotypic features and a marked predisposition to the early development of multiple malignancies. Fewer than 300 affected individuals have been documented worldwide, underscoring the limited therapeutic evidence. Selecting appropriate oncological treatment is challenging because of increased toxicity from cytotoxic agents. Case presentation. We report the case of a 42-year-old woman with marked short stature, micrognathia, generalized cutaneous hyperpigmentation and a history of attenuated familial adenomatous polyposis. In August 2024, she was diagnosed with right-sided colon adenocarcinoma, RAS/BRAF wild-type, pMMR/MSS, stage T2N2M0, and she underwent colectomy with rectal preservation. Concurrent computed tomography revealed a pancreatic mass, and percutaneous biopsy confirmed moderately differentiated pancreatic ductal adenocarcinoma. Multiple pulmonary lesions radiologically suspicious for metastatic disease were also identified. Genetic testing identified two BLM variants reported in compound heterozygosity: c.1237_1240del, p.(Glu413*), classified as potentially pathogenic, and c.98+6T>G, classified as a variant of uncertain significance. The characteristic phenotype and genetic findings supported a clinical diagnosis of Bloom syndrome. Given the synchronous malignancies, suspected pulmonary metastases and underlying genetic susceptibility, FOLFOX6 was initiated at 50% of standard doses. The treatment was well tolerated and resulted in radiological regression of the pancreatic lesion. Following disease progression, the treatment was switched to gemcitabine plus nab-paclitaxel. Subsequent peritoneal and lymph node progression prompted treatment with liposomal irinotecan, 5-fluorouracil, leucovorin and bevacizumab. The subsequent course was marked by lymph node, pulmonary and peritoneal progression, severe nutritional deterioration and death. Conclusions. This case highlights the diagnostic and therapeutic challenges associated with synchronous gastrointestinal malignancies in a patient with a Bloom syndrome phenotype. Treatment individualization, dose reduction and careful toxicity monitoring are essential. Multidisciplinary evaluation is crucial when balancing disease control against treatment-related toxicity in genetically vulnerable patients. Nevertheless, the optimal therapeutic strategy remains uncertain, because specific evidence-based recommendations for this exceptionally rare population are lacking.

Chemotherapy-induced peripheral neuropathy in breast cancer patients: bridging the gap between clinician communication and patient perception

Diana-Maria Pușcașu^1,2, Ioana Creangă-Murariu^1,3,4,5,
Matei-Ioan Rusu³, Mihai-Vasile Marinca^1,5,
Vlad-Adrian Afrăsânie^1,5, Teodora Alexa-Stratulat^1,3,5

1. Oncology-Radiotherapy Department, “Grigore T. Popa” University of Medicine and Pharmacy, Iași, Romania

2. Department of Medical Genetics, “Grigore T. Popa” University of Medicine and Pharmacy, Iași, Romania

3. “Prof. Ostin C. Mungiu” Advanced Research and Development Center for Experimental Medicine (CEMEX), “Grigore T. Popa” University of Medicine and Pharmacy, Iași, Romania

4. Centre for Translational Medicine, Semmelweis University, Budapest, Hungary

5. Department of Medical Oncology, Regional Institute of Oncology Iași, Romania

Introduction. Chemotherapy-induced peripheral neuropathy (CIPN) is a significant toxicity associated with cancer therapy. Early symptom detection relies on patient education and accurate recognition of clinical manifestations and facilitates shared decision-making. This study evaluated the communication of CIPN risk by clinicians compared to its perception by breast cancer patients receiving taxane therapy, aiming to identify discrepancies between delivered information and patient understanding. Materials and method. In this study, two distinct questionnaires were administered to clinicians (n=48) and patients (n=33) to assess counseling timing, education content, monitoring protocols, neuropathy terminology and patient symptom recognition. Comparative analyses utilized Fisher’s exact test, Newcombe hybrid score 95% confidence intervals and the Benjamini-Hochberg correction for false discovery rate control in multiple testing. Results. Clinicians frequently reported addressing neuropathy prior to treatment (91.5%) and reassessing it before each cycle (87.5%). While most patients confirmed receiving pre-treatment counseling (75.8%), only 65.6% recognized the risk of chronic, post-treatment symptoms. Tingling and numbness were well-recognized by patients (77.4%). However, significant communication gaps emerged regarding burning sensations and muscle weakness, which were recognized by 41.9% of patients but disclosed by only 54.2% of clinicians at the initial consultation. Additionally, 48.4% of patients misattributed alopecia to neuropathy, though higher educational attainment strongly inversely correlated with total misconceptions. Conclusions. Although neuropathy is routinely addressed in oncological practice, substantial gaps remain regarding patient recognition and understanding of its full clinical spectrum. Standardizing patient counseling and employing more comprehensive, patient-accessible vocabulary may improve early symptom identification and prompt self-reporting.

Beyond deficient and proficient:
the clinical impact of heterogeneous
MMR expression in gastric cancer

Laura-Elena Stanciu¹, Alexandra Bastian^1,2,
Gianina Micu¹, Sabina Zurac^1,2, A.C. Popa^2,3,
Ioana-Anastasia Cibotariu¹, Alexandra Zeca¹,
Cristina-Alina Sora¹, Cristiana Popp^1,2

1. Department of Pathology, Colentina Clinical Hospital, Bucharest, Romania

2. “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania

3. Department of General Surgery, Colentina Clinical Hospital, Bucharest, Romania

Introduction and objective. Gastric cancer remains a leading cause of cancer-related mortality. Advances in molecular biology enabled its classification into four distinct subtypes, offering new perspectives for targeted therapies. One is microsatellite instability (MSI), suspected in patients with deficient mismatch repair (MMR) status using immunohistochemistry (IHC). While MMR status is typically classified as deficient or proficient, cases exhibiting heterogeneous expression have been reported. These heterogeneous patterns involve deficient MMR subclones, some holding significant clinical relevance. Materials and method. Twenty-nine gastrectomy specimens (collected between 2023 and 2025) were included, comprising 11 total and 18 subtotal gastrectomies. Representative paraffin blocks were selected, and immunohistochemical testing was performed for MLH1, PMS2, MSH2 and MSH6. The expression of MMR proteins was evaluated and categorized as pMMR (proficient), dMMR (deficient) or heterogeneous MMR, defined as sub-clonal and/or intraglandular heterogeneity. Results. IHC revealed a high prevalence of heterogeneous MMR expression: MLH1 22/29 (75.9%), MSH6 17/29 (58.6%), PMS2 12/29 (41.4%) and MSH2 6/29 (20.7%); deficient MMR was rare – 2/29 (6.9%). Heterogeneous MLH1 was significantly more frequent in men (17/19 versus 5/10; p=0.030), while heterogeneous MSH2 was seen exclusively in men (p=0.068). Heterogeneous MLH1 and MSH6 descriptively correlated with aggressive features. Specifically, heterogeneous MLH1 cases frequently exhibited lymphovascular invasion (LVI; 18/22), perineural invasion (PNI; 18/22), pT4 (12/22) and G3 differentiation (13/22). Similarly, MSH6 cases showed high rates of PNI (14/17) and LVI (13/17). Heterogeneous PMS2 and MSH2 were less frequent and showed no consistent association with aggressive clinicopathologic features. Conclusions. In this gastrectomy series, heterogeneous MMR expression is frequent in gastric cancer when evaluating sub-clonal and intraglandular patterns. MMR heterogeneity holds molecular and therapeutic implications. Accurate stratification is crucial, as spatial MMR heterogeneity may directly impact immune checkpoint inhibitor efficacy, guiding personalized oncology.

Integrating miRNA and tumor infiltrating lymphocyte signatures to guide prognostic stratification in stage II colorectal cancer

Daniel Sur¹, Cornelia Braicu², Oana Zănoagă¹, Liviuța Budișan¹, Radu Pîrlog^2,3, Cristina Ciocan², Ekaterina Isachesku²,
Andrada Iovita², Paula Zamfir², Ioana Rus⁴, Andrei Cismaru², Ioana Berindan-Neagoe²

1. Department of Medical Oncology, “Iuliu Hațieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania

2. Institute of Biomedical Research – MEDFUTURE, Department of Genomics,
“Iuliu Hațieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania

3. Département de Pathologie, Hôpitaux Universitaires Henri Mondor,
Assistance Publique-Hôpitaux de Paris (AP-HP), Créteil, France; Université Paris Est Créteil, Créteil, France; INSERMU955, Institut Mondor de Recherche Biomédicale, Créteil, France

4. Department of Pathology, “Octavian Fodor” Regional Institute of Gastroenterology
and Hepatology, Cluj-Napoca, Romania

Corresponding author: Daniel Sur, e-mail: daniel.sur@umfcluj.ro

Introduction. Colorectal cancer (CRC) remains one of the most frequently diagnosed malignancies and a leading cause of cancer-related mortality worldwide. Current approaches to the prognostic stratification of patients with stage II CRC remain inadequate, highlighting the need for additional biomarkers to guide patient management. MicroRNAs (miRNAs) and tumor-infiltrating lymphocytes (TILs) have independently demonstrated prognostic relevance in CRC; however, their combined utility has not been fully elucidated. Materials and method. Formalin-fixed paraffin-embedded (FFPE) tissue specimens obtained from 71 patients with histologically confirmed stage II CRC were retrospectively analyzed. Global miRNA expression profiling was performed in a discovery cohort using Agilent SurePrint Human miRNA microarrays, followed by RT-qPCR validation of selected candidate miRNAs. TILs were assessed by immunohistochemistry staining for CD4⁺ and CD8⁺ T cells. Bioinformatic and statistical analyses, including Ingenuity Pathway Analysis (IPA), were applied to evaluate the prognostic significance of miRNAs, TILs and a model (MIR-TIL) integrating these two parameters. Results. Comparative transcriptomic analysis identified 42 differentially expressed miRNAs between tumor tissue and matched adjacent normal tissue (20 upregulated, 22 downregulated). Increased intratumoral TIL density was significantly associated with improved overall survival (p<0.01). The integrated MIR-TIL model offered superior prognostic stratification compared with either mIRNAs or TILs alone, with this combination of both high TIL density and a favorable miRNA expression profile independently predicting improved clinical outcomes (HR=0.42; 95% CI; 0.24-0.74). IPA analysis implicated the PI3K/Akt, p53 and IL-17/NF-B-associated signaling pathways in these associations. Conclusions. The proposed MIR-TIL model offers a promising integrative biomarker approach to guide risk stratification and adjuvant treatment decisions in stage II colorectal cancer.

Post-induction obstructive shock
and cardiac tamponade in advanced mucinous pulmonary adenocarcinoma:
a management challenge

Andreea-Alexandra Tocuț-Marin

Department of Medical Oncology, “Prof. Dr. Ion Chiricuță” Institute of Oncology, Cluj-Napoca, Romania

Objective. Primary mucinous adenocarcinoma of the lung represents a rare (approximately 10% of lung adenocarcinomas) and aggressive histology characterized by high invasiveness and marked metastatic potential. I report the case of a patient presenting with a massive laterocervical adenopathy and pleural effusions, who decompensated rapidly following the second cycle of systemic therapy, requiring urgent intensive care unit admission. Materials and method. A 50-year-old male, smoker, presented with a painful right laterocervical mass (15/10 cm), odynophagia and cough. Lymph node biopsy confirmed a metastatic mucinous adenocarcinoma of pulmonary origin based on immunohistochemistry. Computed tomography and magnetic resonance imaging established a stage IVB disease due to extensive extrathoracic nodal dissemination (cervical conglomerate 88/70 mm, right axillary/subpectoral 43/28 mm, subcarinal 50 mm), an extensive retrofaryngeal mass (25/115 mm), bilateral pulmonary ground-glass consolidations and baseline effusions (pericardial 14 mm, right pleural 28 mm, left 15 mm). Facing impending upper airway compromise, high-dose dexamethasone was instituted. To achieve rapid response, immediate treatment with carboplatin-paclitaxel was commenced (cycle 1). Following steroid weaning and airway stabilization, pembrolizumab was added to carboplatin-paclitaxel for cycle 2. Results. Within 48 hours post-cycle 2, the patient developed dyspnea, stridor and unrecordable blood pressure. Emergent angio-CT excluded pulmonary embolism but revealed acute serosal expansion: a 35-mm pericardial effusion precipitating overt cardiac tamponade and bilateral pleural effusions, with left upper-lobe atelectasis and 80% hemithoracic opacification. Despite urgent ICU admission, decompressive pericardiocentesis, bilateral pleurocenteses and maximal vasopressor support, worsening lactic acidosis, coagulopathy and ischemic hepatocytolysis proved ultimately fatal. Conclusions. This aggressive subtype of non-small cell lung cancer carries a worse prognosis in more advanced stages and poses substantial diagnostic challenges. Furthermore, bulky thoracic disease predisposes to life-threatening complications, such as cardiac tamponade, shortly after systemic chemo-immunotherapy induction.

Molecular profiling and multimodal management of BRCA2-mutated prostate adenocarcinoma with neuroendocrine differentiation and a metachronous second primary urothelial carcinoma

Diana-Elena Tomescu, Mihaela Pițurcă, Michael Schenker

“Sf. Nectarie” Oncology Center, Craiova, Romania

Introduction. Neuroendocrine differentiation carries a worse prognosis than conventional prostate adenocarcinoma and shifts systemic treatment towards platinum. Roughly a quarter of metastatic patients harbor homologous recombination repair defects, most often BRCA2, which predict response to PARP inhibitors. NCCN and ESMO ask for germline testing, not only somatic. Objective. To present the long-term multimodal management of a young patient with aggressive-variant prostate cancer and a second genitourinary primary, in whom molecular testing opened a targeted therapeutic line. Materials and method. A 51-year-old man was diagnosed in May 2023 with prostate adenocarcinoma, Gleason 9 (4+5), ISUP grade group 5, neuroendocrine differentiation in 10% of the tumor and de novo low-volume nodal metastatic hormone-sensitive disease. He received androgen deprivation therapy (ADT) with six cycles of cisplatin-etoposide for the neuroendocrine component, followed by radiotherapy to the primary and pelvic nodes (46 Gy, boost: 78 Gy). At castration resistance: six cycles of docetaxel, enzalutamide with an LHRH analogue. In November 2025, a metachronous high-grade urothelial carcinoma (pT1 G3 with carcinoma in situ) required intravesical therapy, discontinued for local toxicity. Somatic tumor sequencing was negative for BRCA1/2, while germline testing identified the pathogenic variant BRCA2 c.8331+1G>A. Results. Imaging in February 2026 showed partial response, with regression of retroperitoneal and pelvic nodes. At biochemical progression, olaparib 300 mg twice daily was added to androgen deprivation in August 2026, an option opened by the germline result and supported by NCCN and ESMO after prior androgen receptor pathway inhibition. The treatment is ongoing and well tolerated, with PSA declining from 2.23 to 0.8 ng/mL. Conclusions. Sequential systemic treatment, radiotherapy and the management of a second primary have preserved disease control over three years. The germline result proved decisive and argues for testing in all metastatic prostate cancer, not only castration-resistance.

16S rRNA metataxonomic analysis
of tumor and histologically normal adjacent tissue in colorectal cancer

V. Țuțuianu¹, Valentina Stratan¹, Cristina Popa¹,
M. Novac¹, M. Ciobanu², Veronica Balan¹, N. Balan²,
L. Bejenaru², S. Roșca², O. Pătrașcu²

1. Scientific Laboratory of Cancer Biology, Institute of Oncology, Chișinău, Republic of Moldova

2. Proctology Department, Institute of Oncology, Chișinău, Republic of Moldova

Objective. The evaluation of the taxonomic profile and average relative abundance of microorganisms in tumor tissue compared to histologically normal tissue adjacent to the tumor (NAT) in patients with colorectal cancer (CRC). Materials and method. Paired samples (tumor tissue and NAT) were collected from 15 patients with primary CRC (M0) who underwent surgical resection. The extracted DNA was sequenced using 16S rRNA gene sequencing (V2-V9 regions, Ion GeneStudio S5 platform). Bioinformatics and statistical analyses (R, decontam, phyloseq, vegan, LEfSe, Random Forest) evaluated alpha/beta diversity, taxonomic biomarkers and functional profiles. Results. The median taxonomic richness decreased significantly from 58 in NAT to 47 in the tumor (Wilcoxon test; p<0.01). Beta diversity analysis (PCoA, Bray-Curtis) revealed a global reconfiguration of the microbial community according to tissue type (p=0.013). The genus Campylobacter showed a significant enrichment in tumor tissue (4.72% versus 0.09% in NAT, p=0.002, LDA score = 4.67). Conversely, commensal butyrate-producing taxa, such as Ruminococcus (LDA score = 4.71) and Faecalibacterium (LDA score = 4.40), were severely depleted in tumor tissue. Co-abundance network analysis identified a strong positive correlation between pathogenic taxa, notably forming a Fusobacterium-Parvimonas cluster (p=0.0015). Functional profiling confirmed an increase in potentially pathogenic (p=0.0009), strictly anaerobic (p=0.0026) and biofilm-forming bacteria (p=0.0084), alongside a decrease in butyrate producers (p=0.0015). Discussion and conclusions. The data suggest a destabilization of the colorectal tumor microenvironment. The loss of protective commensal bacteria and the selection of proinflammatory, anaerobic and biofilm-forming species suggest a microenvironment dominated by hypoxia and oxidative stress. Furthermore, the identification of pathogenic co-abundance networks (Fusobacterium-Parvimonas) and a proinflammatory enterotype in some NAT samples supports the presence of a microbiomic “field effect”, suggesting that microbial reconfiguration extends beyond the histological boundaries of the tumor.

Reducing delayed imaging results through workflow optimization between investigation, interpretation
and result validation: a six-month quality improvement project

A.A. Udrea, Raluca Stupar, Bianca Ciortea,
N. Bogdan, C. Arcalean, Patricia Zapartean, Iulia Ignat,
Lorena Pojar

Medisprof Cancer Center, Cluj-Napoca, Romania

Objective. This quality improvement project aimed to reduce the percentage of imaging investigations (computed tomography, magnetic resonance imaging, mammography) with results released beyond the internally agreed deadline, through optimization of the workflow between investigation, interpretation and result validation, within six months. Materials and method. A retrospective analysis of internal data (4789 scans; May-September 2025) established a baseline delay rate of 2.78%. A satisfaction questionnaire (141 patients) and a cause-and-effect analysis identified contributing factors at secretariat, technician, physician and patient level. Using the Institute for Healthcare Improvement (IHI) Model for Improvement, two sequential Plan-Do-Study-Act (PDSA) cycles (October 2025 – March 2026) implemented five measures: individual physician key performance indicators (KPIs), balanced case allocation, additional imaging physicians and secretariat staff, staff retraining and revised call-center scripts. Monthly delay rates were monitored by investigation type through run charts. Results. The overall delay rate decreased from 2.78% to 1.48% (−47%), reaching a minimum of 0.39% in January 2026. CT delays fell from 1.9% to 1.2% (−37%); MRI from 6.9% to 5.5% (−20%), remaining the main contributor (54% of all delays despite 22% of volume). Mammography maintained 0% delay, with a single isolated case in January 2026. A transient increase in February 2026 (1.90%), linked to higher MRI volume, was corrected through reallocation, reaching 1.42% in March. Conclusions. Simultaneous implementation of high-impact measures within sequential PDSA cycles produced a sustained 47% reduction in imaging result delays within six months, confirming that the final target ≤0.75% is achievable. MRI remains the priority risk area, requiring a further PDSA cycle (April-September 2026) to sustain the target for at least three consecutive months and to standardize the improved workflow. Keywords: imaging results delay, workflow optimization, PDSA methodology, quality improvement, radio­logy department