A 25-year-old male patient was admitted to the Department of Pneumonology, Oncology and Allergologybecause of non-small cell carcinoma of the left lung with squamous cell and NOS components. His medicalhistory included an episode of removing asbestos from a roof without protective equipment for several daysapproximately 7 years earlier and a cough lasting for about 6 months. The patient was also a light smokerand had a family history of cancer. Multiple metastases to the lungs, bones, and central nervous system werediagnosed. The patient underwent radiotherapy to the scapula, spine, iliac bone, and occipital lobe. He wasqualified for chemoimmunotherapy with carboplatin, paclitaxel, and cemiplimab. After 2 weeks, the patientwas admitted to the Emergency Department because of breathlessness, dizziness, tinnitus, and nausea.CT and MRI of the cerebrum and cerebellum showed more metastatic lesions (approximately 50) than in the previousexamination; therefore, brain radiotherapy was continued. The patient's condition deteriorated during hospitalization,with severe headache, nausea, and periodic loss of coherent contact. The patient died due to respiratoryfailure and cardiac arrest. This case shows that squamous cell lung cancer can occur in very young people,and physicians must be aware of this possibility even in such a young group of patients. Exposure to carcinogenssuch as asbestos or tobacco smoke may increase the risk of developing lung cancer in this young population.
Cutaneous and soft-tissue metastases from colorectal cancer are uncommon, and involvement of the acral regionsis particularly rare. We report the case of a 28-year-old man with metastatic rectal adenocarcinoma (cT4N1M1)who developed a rapidly progressive lesion involving the left fifth finger during systemic chemotherapy. Despite aninitial biochemical and radiographic response to systemic chemotherapy, the digital lesion appeared and enlargedrapidly. Initially interpreted as a periungual infection, it failed to respond to antibiotic therapy. Hand radiographsdemonstrated soft-tissue involvement without radiographic evidence of osseous destruction, and surgical biopsyconfirmed mucinous metastatic adenocarcinoma of colorectal origin. Germline genetic testing did not identifyLynch syndrome-associated pathogenic variants but identified a heterozygous pathogenic variant in PTPRJ.This case highlights the diagnostic challenges posed by atypical acral metastases, the potential for discordantmetastatic progression during systemic therapy, and the importance of prompt histopathologic confirmation ofrapidly progressive digital lesions in patients with known colorectal cancer.
Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape of advanced non-small celllung cancer (NSCLC) in patients without clinically relevant EGFR, ALK, or ROS1 alterations. However, their efficacyin rare oncogene-driven NSCLC and their optimal integration with targeted therapies remain incompletelydefined. This narrative review summarizes the current evidence regarding ICI-based therapies in NSCLC harboringBRAF, MET exon 14 (METex14) skipping, HER2 (ERBB2), RET, NTRK, and EGFR exon 20 insertion (EGFRex10ins) alterations. Available data demonstrate substantial heterogeneity in immunotherapy responsivenessacross these molecular subgroups. BRAF-mutated NSCLC appears to derive the greatest benefit from ICIs,particularly among patients with smoking-associated tumors, high PD-L1 expression, and TP53 co-mutations.In contrast, ICI monotherapy generally demonstrates modest activity in METex14, HER2-mutated, and EGFRex20ins-positive NSCLC, whereas chemoimmunotherapy produces more favorable outcomes. In addition,RET-rearranged tumors consistently demonstrate poor responses and evidence regarding NTRK fusion-positiveNSCLC remains limited. Across several molecular subgroups, chemoimmunotherapy appears to provide greaterclinical benefit than ICI monotherapy, although targeted therapies remain the preferred treatment strategy owingto their superior efficacy. Overall, the activity of ICIs in rare oncogene-driven NSCLC is strongly influencedby tumor biology and the immune microenvironment. Future prospective studies should focus on identifyingpredictive biomarkers beyond PD-L1 and defining the optimal sequencing and integration of immunotherapywith targeted therapies in molecularly selected patients.
Cancer cachexia is a multifactorial syndrome characterized by involuntary weight loss, skeletal muscle wasting, systemic inflammation, metabolic dysregulation, and progressive functional impairment. It affects approximately 50–80% of patients with advanced malignancies and is associated with reduced quality of life, poorer treatment tolerance, and increased mortality. The pathophysiology of cancer cachexia involves complex interactions between tumor-derived factors and host responses, including chronic inflammation mediated by cytokines such as IL-6, TNF-α, and IL-1β, altered energy metabolism, adipose tissue dysfunction, and enhanced skeletal muscle proteolysis. This narrative review summarizes current knowledge regarding the mechanisms underlying cancer cachexia and evaluates available therapeutic strategies. A structured literature search of PubMed, Scopus, and Web of Science was performed, focusing on clinical trials, systematic reviews, meta-analyses, and key experimental studies published up to 2024. Current evidence indicates that single-agent therapies provide limited benefits due to the heterogeneous and multifactorial nature of cachexia. Consequently, multimodal management combining nutritional support, exercise interventions, pharmacological treatment, and targeted molecular therapies appears to be the most effective approach. Nutritional strategies enriched with omega-3 fatty acids and high-protein formulas may support muscle preservation, while resistance and aerobic exercise improve physical function and metabolic capacity. Pharmacological agents such as anamorelin and anti-inflammatory therapies provide partial symptomatic benefit. Emerging targeted therapies aimed at cytokine signaling and myostatin pathways show promising potential but require further clinical validation. Future progress depends on earlier diagnosis, biomarker-driven phenotyping, and individualized multimodal interventions focused on improving functional outcomes and quality of life.
Nectins and nectin-like molecules (Necls) are calcium-independent immunoglobulin-like cell adhesion molecules with emerging roles in cancer biology, immune regulation, and targeted therapy. Their growing importance as therapeutic targets, immune checkpoint ligands, and predictive biomarkers across many tumour types has been described. NECTIN-1 functions as a major metastasis-suppressor gene in melanoma. NECTIN-1 is deleted in approximately 55% of melanomas, and its loss promotes IGF1-driven melanoma dissemination. Nectin-1 also serves as the entry receptor for oncolytic herpes simplex virus therapy (T-VEC, talimogene laherparepvec). Nectin-2/CD112 and Necl-5/CD155 are key T cell immunoreceptors with Ig and ITIM domains (TIGIT) and are CD226 immune checkpoint ligands. CD155 overexpression predicts resistance to anti-PD-1 therapy and poor prognosis in melanoma, non-small cell lung cancer (NSCLC), and small cell lung cancer (SCLC). Nectin-4 is an oncogenic driver (via PI3K/AKT and SOX-2) in lung cancer and BRAF-inhibitor-resistant melanoma, as well as a validated target of enfortumab vedotin in urothelial carcinoma. Necl-2/CADM1 acts as a tumor suppressor in melanoma and NSCLC, as it suppresses the epithelial-mesenchymal transition (EMT). Data on renal cell carcinoma remain limited. Nectins and Necls constitute a clinically significant protein family in oncology. Currently, Nectin-4 and CD155/TIGIT represent the most therapeutically actionable targets. Combination strategies targeting TIGIT (tiragolumab, ociperlimab, or vibostolimab) with PD-1/PD-L1 blockade are under investigation. Moreover, enfortumab vedotin, an antibody-drug conjugate (ADC) targeting Nectin-4-high tumors, is under investigation in many solid tumors.
INTRODUCTION: Avelumab maintenance is the standard of care for patients with metastatic urothelial carcinoma (mUC) not progressing after first-line platinum-based chemotherapy. Split-dose cisplatin (gemcitabine plus cisplatin day 1 and 8; GC split-dose) extends cisplatin eligibility to patients with creatinine clearance (CrCl) 30–60 mL/min, yet adoption in clinical practice remains inconsistent. The immunological consequences of choosing carboplatin over split-dose cisplatin in this population — particularly with respect to subsequent avelumab activity — have not been examined. We present an interim analysis of the UROCAPOL registry, published ahead of study completion given the potential clinical significance of these findings. MATERIAL AND METHODS: Three objectives were addressed: (1) objective response rate (ORR) to first-line chemotherapy by regimen (gemcitabine + carboplatin — GK, gemcitabine + cisplatin — GC single-dose, GC split-dose); (2) proportion of GK-treated patients with CrCl 30–60 mL/min; and (3) ORR to avelumab maintenance and treatment duration by prior regimen. Statistical comparisons used Fisher’s exact test and chi-squared test. RESULTS: Of 76 patients, 34 received GK, 20 GC single-dose, and 16 GC split-dose. Critically, 22 of 31 GK patients with available CrCl data (71.0%; 64.7% of all GK patients) had CrCl in the 30–60 mL/min range — the recognized eligibility window for split-dose cisplatin — and no GK patient had CrCl below 30 mL/min. Chemotherapy ORRs were: 48.4% (GK), 61.1% (GC single-dose), 91.7% (GC split-dose; GK vs. GC split-dose; p = 0.014). Among 61 patients receiving avelumab maintenance, ORR was 12.5% (GK), 27.8% (GC single-dose), and 66.7% (GC split-dose; 3-group; p = 0.004; GK vs. GC split-dose; p = 0.002). Median avelumab treatment duration was 85.0 days (GK), 105.0 days (GC single-dose), and 183.5 days (GC split-dose); duration data were available for 41 of 61 patients (68.3%), with the remainder likely still on treatment at the data cut. CONCLUSIONS: The majority of GK-treated patients had CrCl values compatible with split-dose cisplatin eligibility, yet received carboplatin. GC split-dose was associated with significantly superior avelumab ORR and approximately twice the treatment duration compared to GK. Mechanistic data suggest split-dose fractionation may optimize immune priming for subsequent checkpoint inhibition. These findings support re-evaluation of platinum selection in patients with CrCl 30–60 mL/min who are candidates for avelumab maintenance.
Rak piersi jest najczęściej rozpoznawanym nowotworem u kobiet na świecie, przy czym 75% stanowią nowotwory hormonozależne, niewykazujące nadekspresji receptora HER2. Pomimo wprowadzenia nowoczesnych terapii celowanych oraz immunoterapii efekt leczenia chorych w stadium zaawansowanym choroby wciąż pozostaje niezadowalający. Mutacje w genach kodujących białka szlaku sygnałowego PI3k/AKT/mTOR występują u 45–55% (40–45% mutacje w PIK3CA, 3–5% mutacje w AKT1, 5–11% mutacje w PTEN) chorych na zaawansowanego HR+, HER2– raka piersi i są kluczowym czynnikiem oporności na terapię hormonalną oraz tę opartą na inhibitorach CDK4/6. Poznanie roli zaburzeń szlaku sygnałowego PI3k/AKT/mTOR w procesie transformacji nowotworowej pozwoliło na wprowadzenie nowych leków do terapii HR+, HER2- raka piersi. Kapiwasertyb (AZD536) jest doustnym, selektywnym inhibitorem blokującym funkcję wszystkich izoform białka AKT wykazującego aktywność kinazy serynowo-treoninowej i stanowiącego element szlaku sygnałowego PI3K/AKT/mTOR. Jego konstytutywna aktywacja stwierdzana jest u ponad 50% chorych na HR+, HER2– raka piersi. Efekt kliniczny kapiwasertybu stosowanego w skojarzeniu z fulwestrantem w leczeniu u chorych na HR+, HER2– zaawansowanego raka piersi, u których doszło do progresji podczas terapii z użyciem inhibitora aromatazy oceniono w badaniu CAPItello-291 wykazując istotne wydłużenie mPFS w populacji chorych objętych badaniem jak też chorych z potwierdzonymi zaburzeniami szlaku PI3l/AKT. Ze względu na niedojrzałość danych nie wykazano wpływu terapii na czas przeżycia całkowitego.
W niniejszym artykule przedstawiono rekomendacje zespołu ekspertów Polskiej Grupy Raka Płuca i Towarzystw Naukowych zajmujących się diagnostyką, kwalifikacją i leczeniem chorych na niedrobnokomórkowego raka płuca w III stopniu zaawansowania klinicznego z zastosowaniem radiochemioterapii (jednoczasowej i sekwencyjnej).
INTRODUCTION: Metastatic pancreatic cancer (mPC) is a highly aggressive disease associated with elevated rates of morbidity and mortality, and long-term survival remains poor. New therapeutic options, such as gemcitabine plus nab-paclitaxel (GEM-NAB), demonstrate statistically significant improvements in both overall survival (OS) and progression-free survival (PFS). Evidence-based data regarding the management of mPC in the elderly population remain limited. MATERIAL AND METHODS: This retrospective study analyzed a total of 245 patients with mPC treated with first-line GEM-NAB between February 2017 and January 2025. Of these, 143 (58.4%) were aged ≥ 65 years, including 88 (61.5%) women and 55 (38.5%) men. RESULTS: The median PFS was 6.07 months (95% CI: 5.24–6.89), and the median OS was 9.33 months (95% CI 8.64–10.03). The most common adverse events (AEs) were anemia, fatigue, neutropenia, peripheral neuropathy, and thrombocytopenia. No significant differences in the safety profile were observed between the older and younger patient groups; notably, the incidence of grade 4 toxicities was comparable. Dose modifications were required in 69.2% of cases to effectively manage AEs. Alcohol consumption and CEA levels were identified as independent prognostic factors for both OS and PFS. CONCLUSIONS: Our findings demonstrate that GEM-NAB is a safe and effective regimen for elderly patients in good clinical condition. Proactive dose modifications are essential to maintain treatment tolerability without compromising efficacy.
Introduction. Early phase (phase I-II) clinical trials in oncology increasingly evaluate biologically active agents and combination strategies. However, outcomes in patients treated in contemporary studies remain incompletely defined. We aimed to assess treatment response and survival outcomes in patients enrolled in early phase oncology trials at a single academic center. Material and methods. This retrospective analysis included adult patients with malignant tumors treated in phase I-II clinical trials between 2019 and 2024. Treatment outcomes included overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Survival outcomes were estimated using the Kaplan-Meier method and compared across clinically relevant subgroups. Results. A total of 146 patients were included. Objective responses were observed in 60 patients, corresponding to an ORR of 41.1%, and disease control was achieved in 83.6% of patients. Median OS was 1.44 years, with estimated 1-year and 2-year OS rates of 63.3% and 38.8%. Median PFS was 0.63 years, with 1-year and 2-year PFS rates of 38.6% and 26.2%, respectively. Higher response rates and numerically longer survival outcomes were observed in patients treated in earlier lines of therapy. Tumor type significantly influenced both OS and PFS, with the most favorable outcomes observed in lymphoid malignancies. No statistically significant differences in survival were observed according to treatment regimen, trial phase, or disease stage. Conclusions. In the real-world cohort, participation in early phase clinical trials was associated with meaningful antitumor activity and clinically relevant survival outcomes, supporting early phase studies as a therapeutic option for selected patients with advanced malignancies.
Introduction. The choice of cisplatin regimen concomitant with radiotherapy (CRT) has been a matter of debate in recent years. In the adjuvant setting, the phase III JCOG 1008 trial has demonstrated non-inferiority of the weekly dose (qW) regimen in terms of overall survival. In the radical setting, the phase III ConCERT trial did the same in terms of 2-year local control rate. However, data from the 6-year results of the phase III clinical trial by Noronha et al. (adjuvant setting) and the meta-analysis conducted by Zhu, J. et al. (2012) (radical setting) positions the three-weekly (q3W) regimen as superior. Material and methods. This was a retrospective, descriptive, comparative observational non-inferiority study (delta = 10%). We analyzed data from 58 patients with HNSCC treated with CRT (36 q3W, 22 qW; 44.8% adjuvant setting and 53.4% radical setting) between January 2019 and December 2023. Patients in the qW arm were less fit than those treated with q3W in our sample. Results. We found no difference in median cumulative cisplatin dose or in G3 toxicity rate. With a median follow-up of 27 months (q3W) and 14 months (qW), the recurrence, progression, or exitus rate was 19.4%, 22.2%, and 25% (q3W) vs. 13.6%, 18.2%, and 18.2% (qW). No significant differences were found in the Kaplan-Meier survival estimates (long-rank test p: local/distant-DFS = 0.93; PFS = 0.91; OS = 0.71). Conclusions. Tolerability and compliance of the qW regimen in a less fit patient population was similar to that of the fitter q3W patients. No differences were found in DFS, PFS, and OS.
Adenosquamous carcinoma of the lung is a rare and aggressive subtype of non-small cell lung cancer, consisting of adenocarcinoma and squamous cell carcinoma components. The pathogenesis remains unclear, the diagnosis is challenging and underrecognized, and the therapeutic strategy requires further investigation. We report a case of a patient with adenosquamous lung cancer presenting different molecular profiles between the two tumor components sampled from the primary lesion and metastatic lymph nodes, who was treated with tyrosine kinase inhibitors (TKIs). In addition, we summarised the available evidence on TKI effectiveness in epidermal growth factor receptor (EGFR)-mutated adenosquamous carcinoma, suggesting potential therapeutic benefit in this subgroup with emphasis on existing diagnostic limitations and the need to deepen the current knowledge.
Apocrine carcinoma is a rare adnexal malignancy lacking standardized treatment strategies in the metastatic setting, with systemic therapies often yielding limited and short-lived responses. The role of radiotherapy in this context remains poorly defined. We report the case of a 49-year-old man with metastatic axillary apocrine carcinoma in whom immunotherapy was contraindicated due to active autoimmune disease requiring chronic immunosuppression. Following surgery and multiple lines of systemic chemotherapy, the patient developed locoregional and distant progression, including cutaneous, nodal, and skeletal metastases. Radiotherapy delivered to the axilla (30 Gy in 10 fractions) resulted in complete regression of clinically evident cutaneous disease, with durable local control despite ongoing systemic progression outside the irradiated field. Subsequent palliative radiotherapy to symptomatic bone metastases (20 Gy in 5 fractions) achieved prompt and sustained pain relief, accompanied by radiological evidence of recalcification. All treatments were well tolerated, with no observed acute or late toxicities. The repeated responses to radiotherapy observed in this case support the radiosensitivity of apocrine carcinoma and suggest its potential role as an effective local treatment modality across both curative and palliative settings. In metastatic disease, where standardized systemic options are lacking, radiotherapy may represent a valuable component of multidisciplinary management, particularly when other therapies are ineffective or contraindicated.
