Centrum Onkologii-Instytutu

Purpose The dermatological management of cancer patients with cutaneous adverse events occurring during and after oncologic treatment is known as supportive oncodermatology. This includes prevention, early identification, and mitigation of dermatologic toxicities. The aim of the international RESCUE (Residents’ survey on training of dermatology residents in supportive oncodermatology) study was to ascertain the current level of expertise in supportive oncodermatology among dermatology residents. Methods The European Task Force “Dermatology for cancer patients” and the US Oncodermatology Society developed an online questionnaire with 30 multiple-choice items. Responses were collected using qualitative ordinal data (yes/no, 1–5 ratings) and multiple-choice options. Ordinal range results were analyzed by aggregating responses 1 + 2 + 3 versus 4 + 5, with 5 representing the highest grade (“extremely confident” or “full training”). Results A total of 442 dermatology residents from 20 countries replied. These participants reported receiving less comprehensive training in supportive oncodermatology (only 41% receiving complete training) compared to immunodermatology (75%), cutaneous oncology (75%), dermoscopy (64%), and dermatologic surgery (50%). Only 17% of the residents reported feeling confident in managing the dermatological toxicities associated with anticancer treatments. Residents also indicated receiving less education regarding toxicities related to endocrine therapies (28%). In particular, lower levels of competence were reported in managing nail, hair, and oral toxicities. A significant majority of residents (98%) deemed it essential to enhance training in dermatological toxicities associated with anticancer therapies during their oncology residency. Conclusion The RESCUE study represents the first project assessing residents’ education in supportive oncodermatology. To enable future generations of dermatologists to provide enhanced care for cancer patients, supportive oncodermatology training should be integrated in residency programs worldwide, corresponding to training in other subspecialties. A more practical approach should also be incorporated, including extended training in hair, nail, and oral toxicities, enhancing the competencies of dermatology residents in all countries.

Clinical question In adult patients undergoing colonoscopy for any indication (screening, surveillance, follow-up of positive faecal immunochemical testing, or gastrointestinal symptoms such as blood in the stools) what are the benefits and harms of computer-aided detection (CADe)? Context and current practice Colorectal cancer (CRC), the third most common cancer and the second leading cause of cancer-related death globally, typically arises from adenomatous polyps. Detection and removal of polyps during colonoscopy can reduce the risk of cancer. CADe systems use artificial intelligence (AI) to assist endoscopists by analysing real-time colonoscopy images to detect potential polyps. Despite their increasing use in clinical practice, guideline recommendations that carefully balance all patient-important outcomes remain unavailable. In this first iteration of a living guideline, we address the use of CADe at the level of an individual patient. Evidence Evidence for this recommendation is drawn from a living systematic review of 44 randomised controlled trials (RCTs) involving more than 30 000 participants and a companion microsimulation study simulating 10 year follow-up for 100 000 individuals aged 60-69 years to assess the impact of CADe on patient-important outcomes. While no direct evidence was found for critical outcomes of colorectal cancer incidence and post-colonoscopy cancer incidence, low certainty data from the trials indicate that CADe may increase positive endoscopy findings. The microsimulation modelling, however, suggests little to no effect on CRC incidence, CRC-related mortality, or colonoscopy-related complications (perforation and bleeding) over the 10 year follow-up period, although low certainty evidence indicates CADe may increase the number of colonoscopies performed per patient. A review of values and preferences identified that patients value mortality reduction and quality of care but worry about increased anxiety, overdiagnosis, and more frequent surveillance. Recommendation For adults who have agreed to undergo colonoscopy, we suggest against the routine use of CADe (weak recommendation). How this guideline was created An international panel, including three patient partners, 11 healthcare providers, and seven methodologists, deemed by MAGIC and The BMJ to have no relevant competing interests, developed this recommendation. For this guideline the panel took an individual patient approach. The panel started by defining the clinical question in PICO format, and prioritised outcomes including CRC incidence and mortality. Based on the linked systematic review and microsimulation study, the panel sought to balance the benefits, harms, and burdens of CADe and assumed patient preferences when making this recommendation Understanding the recommendation The guideline panel found the benefits of CADe on critical outcomes, such as CRC incidence and post-colonoscopy cancer incidence, over a 10 year follow up period to be highly uncertain. Low certainty evidence suggests little to no impact on CRC-related mortality, while the potential burdens—including more frequent surveillance colonoscopies—are likely to affect many patients. Given the small and uncertain benefits and the likelihood of burdens, the panel issued a weak recommendation against routine CADe use. The panel acknowledges the anticipated variability in values and preferences among patients and clinicians when considering these uncertain benefits and potential burdens. In healthcare settings where CADe is available, individual decision making may be appropriate. Updates This is the first iteration of a living practice guideline. The panel will update this living guideline if ongoing evidence surveillance identifies new CADe trial data that substantially alters our conclusions about CRC incidence, mortality, or burdens, or studies that increase our certainty in values and preferences of individual patients. Updates will provide recommendations on the use of CADe from a healthcare systems perspective (including resource use, acceptability, feasibility, and equity), as well as the combined use of CADe and computer aided diagnosis (CADx). Users can access the latest guideline version and supporting evidence on MAGICapp, with updates periodically published in The BMJ .

Importance Treating locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) involves any combination of surgery, radiation, and chemotherapy, followed by routine monitoring for local recurrence or distant metastases. Given the poor patient outcomes, a significant unmet clinical need for improved treatment options remains. Objective To evaluate efficacy and safety of maintenance atezolizumab in patients with LA SCCHN at high risk of disease progression after multimodal definitive treatment. Design, Setting, and Participants IMvoke010 was a phase 3, global, double-blind, randomized clinical trial. Patients were recruited at 128 sites in 23 countries between April 3, 2018, and February 14, 2020 (clinical cutoff date: September 27, 2023). Eligible patients had LA SCCHN (stage IVa/IVb involving the oral cavity, larynx, hypopharynx, or human papillomavirus–negative oropharynx, or stage III human papillomavirus–positive oropharynx [ AJCC Cancer Staging Manual, eighth edition]) without disease progression after multimodal definitive treatment. Intervention Patients were randomized (1:1) to receive atezolizumab 1200 mg or placebo every 3 weeks for 1 year or until disease recurrence, disease progression, unacceptable toxicity, or consent withdrawal. Main Outcomes and Measures The primary end point was investigator-assessed event-free survival. Other end points included overall survival and safety. Results Overall, 406 patients were randomized to receive atezolizumab (n = 203) or placebo (n = 203); baseline demographics were balanced between both treatment groups (<65 years, 142 [70.0%] vs 155 [76.4%]; male, 168 [82.8%] vs 174 [85.7%]; Asian, 68 [35.6%] vs 61 [31.0%]; Black, 1 [0.5%] vs 1 [0.5%]; and White, 121 [63.4%] vs 135 [68.5%], respectively). At clinical cutoff (median follow-up, 46.5 months), median investigator-assessed event-free survival was 59.5 months (95% CI, 46.8 to not estimable) with atezolizumab vs 52.7 months (95% CI, 41.4 to not estimable) with placebo (hazard ratio, 0.94; 95% CI, 0.70-1.26; P = .68). There was no difference in overall survival between atezolizumab and placebo (24-month overall survival, 82.0% vs 79.2%, respectively). No new or unexpected safety signals were identified. Conclusions and Relevance In this study, atezolizumab did not improve clinical outcomes in patients with LA SCCHN at high risk of disease progression after multimodal definitive treatment. These data contribute to evidence on the limited activity of checkpoint inhibitors in the global population of this disease setting. Overall, the role of immunotherapy for patients with LA SCCHN remains to be determined. Trial Registration ClinicalTrials.gov Identifier: NCT03452137

Background We report the results of the pre-planned secondary analysis of radiologic responses (RRs) of ISG-STS 1001, a randomized trial comparing anthracycline + ifosfamide (AI) versus histology-tailored (HT) neoadjuvant chemotherapy for primary localized high-risk soft-tissue sarcomas of the extremities and trunk wall. Patients and methods Patients with undifferentiated pleomorphic sarcoma (UPS), leiomyosarcoma (LMS), malignant peripheral nerve sheath tumor, synovial sarcoma or myxoid liposarcoma (MLPS) were randomized, whereas patients with myxofibrosarcoma, pleomorphic liposarcoma, pleomorphic rhabdomyosarcoma or unclassified sarcoma were included in the observational arm (O) and treated with AI. Patients with UPS, LMS or MLPS needing concurrent preoperative radiotherapy were included in O. We evaluated associations between: disease-free survival (DFS)/overall survival (OS) and centrally reviewed RR, assessed with RECIST 1.1 and as percent dimensional variation (D; both dichotomized and continuous); DFS/OS and histology; RR and histology. Results Four hundred and thirty-five patients were included (287 randomized, 148 observed). The analysis of RRs comprised 236 patients (154 randomized, 82 observed) with measurable disease and available for central review. RECIST best responses were: 28 (11.9%) partial response (PR), 195 (82.6%) stable disease (SD), 13 (5.5%) progressive disease (PD). RECIST significantly correlated with DFS [PD versus PR: hazard ratio (HR) 8.18, 95% confidence interval (CI) 2.96-22.58; SD versus PR: HR 2.96, 95% CI 1.30-6.75] and OS (PD versus PR: HR 12.61, 95% CI 3.40-46.84; SD versus PR: HR 4.24, 95% CI 1.34-13.47). The median value of D was −1.6%. Patients with D >−1.6% had worse clinical outcomes than those with D <−1.6% (DFS: HR 1.73, 95% CI 1.19-2.50; OS: HR 1.86, 95% CI 1.21-2.86). D in continuous scale inversely correlated with DFS (HR 1.53, 95% CI 1.25-1.87) and OS (HR 1.78, 95% CI 1.41-2.25). Conclusions These results confirm the prognostic value of RRs as per RECIST and D and demonstrate that any variation in size predicts the proportional efficacy of treatment.

Background/Objectives: Patients with chronic lymphocytic leukemia (CLL) are susceptible to infections that can affect their clinical outcomes. Aims: The aims of this study were to assess the following: (1) the incidence of pneumonia in CLL patients treated with venetoclax-based regimens in a real-world setting, (2) the risk factors for event-free survival (EFS), and (3) overall survival (OS). Methods: This multicenter study included 322 patients from eight centers. Univariable and multivariable analyses (MVA) were performed, with the development of pneumonia during venetoclax-based treatment and OS as outcomes. Results: The most common complication was neutropenia (59%). During treatment with venetoclax-based regimens, 66 (20%) patients developed pneumonia—50 (23%) patients in the rituximab-plus-venetoclax (R-VEN) group and 13 (16%) patients in the obinutuzumab-plus-venetoclax (O-VEN) group (p = 0.15). Chronic obstructive pulmonary disease (COPD)/asthma, splenomegaly, elevated creatinine, and anemia < 8 g/dL were the risk factors for EFS in MVA (HR = 2.08, 95%CI 1.16–3.74, p = 0.014; HR 1.73, 95%CI 1.08–2.78, p = 0.02; HR 2.13, 95%CI 1.10–4.11, p = 0.03, HR 3.58, 95%CI 2.18–5.89, p < 0.001, respectively). Relapsed/refractory (R/R) CLL patients treated with R-VEN with pneumonia had worse OS than those without (p < 0.001). In patients treated with O-VEN, median OS did not differ between patients with and without pneumonia (p = 0.45). Conclusions: Our real-world study showed that pneumonia during venetoclax treatment occurs more frequently than reported in registration trials and has a negative impact on OS, especially in patients with R/R CLL who are treated with R-VEN. Neutropenia is not a risk factor for pneumonia.

Radial forearm free flap (RFFF) is one of the most popular free flaps in the history of reconstructive microsurgery. Due to its characteristics, it has found its main application in reconstructions in the head and neck region. Before harvesting this flap due to the removal of 1 of the 2 major forearm arteries, an Allen test has historically been recommended. However, is it necessary to use this test in every patient? During the period of 2013 to 2023, 237 RFFF reconstructions were performed on 220 patients. Each surgeon performing a given procedure received a questionnaire to complete, which concentrated on only 2 questions, each had 2 possible answers. The first, whether the Allen test was performed before harvesting the radial forearm free flap, and second, if there was, whether it ever resulted in the change of the approach to reconstruction. In a whole analyzed group of 237 harvested flaps, there were no acute or chronic ischemic complications regarding the hand itself. Three surgeons who performed the RFFF most frequently stated that they had never done Allen test during the last decade. The remaining number of operators have assured that they always have used Allen test, but the result has never forced them to change the approach. Our study shows that the Allen test has limited utility in patients where the radial forearm flap was harvested from a previously intact donor site.

Recent years have brought new, highly effective systemic treatments to clinical practice, which can be used to treat patients with locally advanced or metastatic skin cancers. Using these regimens in neoadjuvant strategy influences surgical treatment by facilitating surgical resection, avoiding extensive resections with complex reconstructions and even omitting surgery in some cases. Integrating systemic therapy with surgery is ongoing and requires novel quality measures of surgical treatment to capture the clinical benefits of multidisciplinary strategies better. The Textbook Outcome (TO) is a novel measure of surgical quality, which captures the short-term outcomes of surgery and reflects long-term survival. Textbook Outcomes match a particular type of surgery, are intuitive to interpret, and may be widely applied in surgical oncology and general surgery. Therefore, this review aims to describe recent findings on neoadjuvant skin cancer treatment and their implications for surgical proceedings in the context of Textbook Outcomes.

Purpose Dermatologic management of cancer patients with cutaneous adverse events, acquired during and after oncologic treatments, is known as supportive oncodermatology. This subspecialty within dermatology includes the prevention, early identification, and mitigation of dermatologic toxicities affecting the skin, hair, nails, and mucous membranes resulting from chemotherapy, targeted therapies, immunotherapy, endocrine therapies and radiation therapy. Methods The European Academy of Dermatology and Venereology (EADV) Task Force “Dermatology for Cancer Patients,” in partnership with the US Oncodermatology Society conducted this international questionnaire-based study RESCUE (RESIDENTS SURVEY ON TRAINING OF DERMATOLOGY RESIDENTS IN SUPPORTIVE ONCODERMATOLOGY), aiming to evaluate the current state of knowledge and training in supportive oncodermatology. Results 442 dermatology residents from 20 countries participated in the RESCUE study. Main results showed that dermatology residents declared to be less trained in supportive oncodermatology (only 41% received complete training) compared to immunodermatology (75%), cutaneous oncology (75%), dermoscopy (64%) and dermatologic surgery (50%). Only 17% of residents affirmed feeling comfortable dealing with dermatological toxicities of anticancer treatments. Residents stated being less educated in the management of dermatological toxicities of endocrine therapies (28%). They felt less qualified in nail, hair and oral toxicities. 98% of residents considered that improving training on dermatological toxicities of anticancer therapies is important during residency. Conclusion A specific dedicated residency program including a more practical approach, together with an extended training in endocrine therapies, as well as hair, nail and oral toxicities, would improve the skills of dermatology residents in the management of cutaneous adverse events of anticancer therapies.

A survey regarding utilisation of brachytherapy was distributed to European brachytherapy professionals. Eighty replies from 26 countries were received, two of which were outside Europe. The replies showed that brachytherapy is still widely used. The main indications for brachytherapy are gynaecological and prostate cancer, with >80 % of the responding countries performing brachytherapy for these indications. There is on average one brachytherapy centre per 0.8 million inhabitants, ranging from 0.4 per million to 2.3 per million inhabitants. The organisation of brachytherapy on national levels also varies from country to country, with less than half of the countries having a central brachytherapy registry. All in all, the survey shows that brachytherapy still plays a role on modern radiotherapy, but the field could benefit from a stronger collaboration both nationally and internationally.

INTRODUCTION: The abrupt transition to remote learning caused by the COVID-19 pandemic clearly indicated the need to implement radical technological and institutional changes to the current approach to teaching. Virtual reality (VR) and artificial intelligence (AI) assisted programs have emerged as the new and effective methods utilized in education and medical training. MATERIAL AND METHODS: The Virtual Clinic (VC) is a new online application developed by Polish medical universities which implement AI algorithms to teach students the medical interview including obtaining patients medical history, performing a physical examination as well as diagnostics and treatment planning. Our study enrolled 164 medical students who tested the VC and completed an online questionnaire. RESULTS: The results of the survey showed that 93.9% of the respondents believe that the VC will prove effective as an educational tool supporting teaching at faculties of medicine and health sciences. CONCLUSIONS: Our preliminary experiences suggest that the use of AI assisted programs such as the VC seems highly anticipated and justified in medical higher education.

Breast cancer (BC) is a leading cause of death among women, with approximately 30% HER2-positive (HER2+). Although HER2-targeted therapies have improved outcomes for patients with HER2+ metastatic breast cancer (mBC), significant clinical challenges and prognostic variability remain. Tumor-infiltrating lymphocytes (TILs) have emerged as prognostic and predictive biomarkers in various tumors, including BC, but their role in HER2+ mBC is poorly understood. This multicentric retrospective cohort study evaluated the prognostic significance of TILs in 110 patients with HER2+ mBC treated with pertuzumab, trastuzumab, and taxane-based chemotherapy at two Italian institutes from June 2013 to May 2024.TILs were assessed on metastatic or primary tumor samples. High TILs levels (> 5%) were independently associated with longer PFS and OS. TILs levels were higher in primary tumours than in metastases (p=0.009), with significant variation by metastatic site. These findings underscore the potential of TILs as prognostic biomarkers in HER2+ mBC, necessitating further prospective studies.

Psoriasis and psoriatic arthritis are chronic inflammatory conditions that constitute a significant global health burden due to their prevalence and impact on quality of life. A deeper comprehension of psoriasis and psoriatic arthritis pathogenesis has recently led to the emergence of novel classes of biologics targeting the IL-23/Th17 pathway. The specific role of interleukin-12, -23, and -17 in cancer as either promoters or inhibitors is under investigation in various studies. Here, we explore the potential role of interleukin-12, -23, and -17 in the development of skin tumours as well as the safety of using their inhibitors in the treatment of psoriasis and psoriatic arthritis, particularly in relation to the risk of melanoma and non-melanoma skin cancer (NMSC) development.

T cell inhibitory mechanisms prevent autoimmune reactions, while cancer immunotherapy aims to remove these inhibitory signals. Chronic ultraviolet (UV) exposure attenuates autoimmunity through promotion of poorly understood immune-suppressive mechanisms. Here we show that mice with subcutaneous melanoma are not responsive to anti-PD1 immunotherapy following chronic UV irradiation, given prior to tumor injection, due to the suppression of T cell killing ability in skin-draining lymph nodes. Using mass cytometry and single-cell RNA-sequencing analyzes, we discover that skin-specific, UV-induced suppression of T-cells killing activity is mediated by upregulation of a Ly6ahigh T-cell subpopulation. Independently of the UV effect, Ly6ahigh T cells are induced by chronic type-1 interferon in the tumor microenvironment. Treatment with an anti-Ly6a antibody enhances the anti-tumoral cytotoxic activity of T cells and reprograms their mitochondrial metabolism via the Erk/cMyc axis. Treatment with an anti-Ly6a antibody inhibits tumor growth in mice resistant to anti-PD1 therapy. Applying our findings in humans could lead to an immunotherapy treatment for patients with resistance to existing treatments.

Simple Summary Adaptive proton therapy (APT) is an evolving approach to proton beam scanning treatment planning. We performed dosimetric study on two groups of head and neck (H&N) patients to evaluate the influence of plan adaptation on planning target volume (PTV) and organs at risk (OARs) doses, resulting from the changes in patient anatomy observed in control computed tomography (CT). The adapted treatment plans, which incorporated the changes observed in the control CT images, statistically improved mostly PTV coverage compared to initial plan. Study shows that applying adaptive procedures in clinical workflow may increased efficiency by controlling the proper irradiation of the treated area for H&N cancer patients. Abstract Applying a proton beam in radiotherapy enables precise irradiation of the tumor volume, but only for continuous assessment of changes in patient anatomy. Proton beam range uncertainties in the treatment process may originate not only from physical beam properties but also from patient-specific factors such as tumor shrinkage, edema formation and sinus filling, which are not incorporated in tumor volume safety margins. In this paper, we evaluated variations in dose distribution in proton therapy resulting from the differences observed in the control tomographic images and the dosimetric influence of applied adaptive treatment. The data from weekly computed tomography (CT) control scans of 21 patients, which serve as the basis for adaptive radiotherapy, were used for this study. Dosimetric analysis of adaptive proton therapy (APT) was performed on patients with head and neck (H&N) area tumors who were divided into two groups: patients with tumors in the sinus/nasal area and patients with tumors in the brain area. For this analysis, the reference treatment plans were forward-calculated using weekly control CT scans. A comparative evaluation of organ at risk (OAR) dose-volume histogram (DVH) parameters, as well as conformity and homogeneity indices, was conducted between the initial and recalculated dose distributions to assess the necessity of the adaptation process in terms of dosimetric parameters. Changes in PTV volume after replanning were observed in seventeen patient cases, showing a discrepancy of over 1 cm3 in ten cases. In these cases, tumor progression occurred in 30% of patients, while regression was observed in 70%. The statistical analysis indicates that the use of the adaptive planning procedure results in a statistically significant improvement in dose distribution, particularly in the PTV area. The findings led to the conclusion that the adaptive procedure provides significant advantages in terms of dose distribution within the treated volume. However, when considering the entire patient group, APT did not result in a statistically significant dose reduction in OARs (α = 0.05).

Introduction Extramedullary plasmacytoma (EMP) is an uncommon solitary tumor originating from neoplastic plasma cells located outside the bone marrow. Despite its rarity, the occurrence of EMP without a concurrent diagnosis of multiple myeloma (MM) is considered extremely rare. Approximately 80–90% of EMP cases are found in the head and neck region, with a higher incidence in men aged between 50 and 60 years. The current treatment modalities include radiotherapy (RT) as a first-line approach, with surgery or chemotherapy regarded as other therapeutic options. While RT proves effective in the majority of EMP cases, there are instances where the tumor remains refractory to radiation. In this case report, we present an unusual scenario of EMP resistant to RT without concurrent signs of multiple myeloma which was successfully treated with surgery followed by systemic therapy. Case report A 72-year-old male was admitted to the Head and Neck Cancer Clinic with a 6-month history of swallowing difficulties. He denied experiencing weight loss or pain on swallowing. Basic laboratory tests yielded results within normal limits, except for beta-2 microglobulin. Physical examination revealed an enlarged submandibular lymph node on the right side. Fiberoptic examination identified a soft tissue polypoid mass within the right piriform fossa, slightly protruding into the vocal slit. A CT scan displayed a well-circumscribed 2 cm polypoid, homogeneously enhancing soft tissue mass adjacent to the posterior surface of the epiglottis and the right side of the tongue base. Bone marrow biopsy revealed no abnormalities, and there were no clinical or laboratory signs of multiple myeloma. Based on the tumor biopsy results and imaging studies, a diagnosis of EMP was made. Due to the lack of response to RT, surgical removal of the tumor was pursued, followed by systemic therapy. Ultimately, the patient achieved full recovery with effective disease control. Conclusion In conclusion, EMP without concurrent multiple myeloma is an exceedingly rare condition that demands a multidisciplinary approach for both diagnosis and treatment. Moreover, although RT continues to be the primary standard treatment for EMP, in some cases other therapeutic regimens prove to be successful.

Background: Allergen immunotherapy (AIT) is a well-established and efficient method of causative treatment for allergic rhinitis, asthma and insect venom allergy. Traditionally, a recent history of malignant neoplasm is regarded as a contraindication to AIT due to concerns that AIT might stimulate tumor growth. However, there are no data confirming that the silencing of the Th2 response affects prognosis in cancer. Objectives: The aim of this study was to investigate frequency of malignant tumors in patients undergoing AIT and the association between AIT and cancer-related mortality. Patients and Methods: A group of 2577 patients with insect venom allergy undergoing AIT in 10 Polish allergology centers was screened in the Polish National Cancer Registry. Data on cancer type, diagnosis time and patients’ survival were collected and compared with the general population. Results: In the study group, 86 cases of malignancies were found in 85 patients (3.3% of the group). The most common were breast (19 cases), lung (9 cases), skin (8 cases), colon and prostate cancers (5 cases each). There were 21 cases diagnosed before AIT, 38 during and 27 after completing AIT. Laplace’s crude incidence rate was 159.5/100,000/year (general population rate: 260/100,000/year). During follow-up, 13 deaths related to cancer were revealed (15% of patients with cancer). Laplace’s cancer mortality rate was 37.3/100,000/year (general population rate: 136.8/100,000/year). Conclusions: Malignancy was found in patients undergoing immunotherapy less often than in the general population. Patients with cancer diagnosed during or after AIT did not show a lower survival rate, which suggests that AIT does not affect the prognosis.

Cancer progression and therapeutic resistance are closely linked to the acquisition of a stemness phenotype. In this context, we introduce a novel protein expression-based stemness index (PROTsi) designed to evaluate oncogenic dedifferentiation in relation to histopathology, molecular features, and clinical outcomes in tumor samples. The methodology involved the application of a machine learning model to predict the stemness molecular phenotype, leveraging proteomic data. The prediction model was built from human pluripotent stem cells from the Human Induced Pluripotent Stem Cells Consortium (HipSci). Using datasets sourced from the Clinical Proteomic Tumor Analysis Consortium (CPTAC) across eleven distinct tumor types, we validate PROTsi's effectiveness in accurately quantifying stem-like features. Integrating the PROTsi with gene expression, DNA methylation, microRNA expression, copy number alteration, and protein post-translational modification data such as protein acetylation, glycosylation, and phosphorylation, we unveiled proteogenomic associations related to stemness. This comprehensive analysis enabled the identification of proteins and modified proteins functioning as active nodes within transcriptional networks, thereby steering the cancer aggressiveness. Proteins highly correlated with stemness were identified as potential drug targets both tumor-specific and shared among tumor types. The stemness-associated proteins we identified demonstrate prognostic value for clinical outcomes, as confirmed through immunohistochemistry in independent samples. This underscores PROTsi's efficacy as a valuable tool for selecting both prognostic protein and drug targets. This dual functionality enhances its utility in customizing anti-cancer therapy and propels the clinical development of effective cures for diverse cancer patient populations. In conclusion, our study not only introduces PROTsi as a robust method for evaluating stemness in cancer but also sheds light on potential opportunities for targeted therapies, emphasizing the significance of personalized treatment strategies in the pursuit of more effective cancer interventions. Citation Format: Iga Kołodziejczak-Guglas, Renan Simões, Elizabeth G. Demicco, Rossana L. Segura, Alexander J. Lazar, Weiping Ma, Erik Storrs, Francesca Petralia, Antonio Colaprico, Felipe da Leprevost, Pietro Pugliese, Michele Ceccarelli, Alexey I. Nesvizhski, Bożena Kamińska, Bing Zhang, Henry Rodriguez, Mehdi Mesri, Ana I. Robles, Clinical Proteomic Tumor Analysis Consortium, Li Ding, Tathiane M. Malta, Maciej Wiznerowicz. Deciphering oncogenic dedifferentiation: A proteomic approach to quantifying stemness scores and unveiling druggable targets [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB004.

Key Clinical Message Identifying myeloid sarcoma in rare locations is a diagnostic challenge and requires careful evaluation. The optimal management of extramedullary disease requires further investigation, but tissue biopsy and a personalized approach are crucial. Abstract Herein, we describe an unusual case of acute myeloid leukemia presenting with an isolated involvement of the temporal bone after a complete remission of systemic disease for more than a year. The clinical, radiological, and pathological features are discussed, highlighting the importance of considering differential diagnoses and appropriate management.