Background: Recent publications underscore the need for updated recommendations addressing less radical surgery for <2 cm tumors, induction chemotherapy, or immunotherapy for locally advanced stages of cervical cancer, as well as for the systemic therapy for recurrent or metastatic cervical cancer. Aim: To summarize the current evidence for the diagnosis, treatment, and follow-up of cervical cancer and provide evidence-based clinical practice recommendations. Methods: Developed according to AGREE II standards, the guidelines classify scientific evidence based on the Agency for Health Technology Assessment and Tariff System criteria. Recommendations are graded by evidence strength and consensus level from the development group. Key Results: (1) Early-Stage Cancer: Stromal invasion and lymphovascular space involvement (LVSI) from pretreatment biopsy identify candidates for surgery, particularly for simple hysterectomy. (2) Surgical Approach: Minimally invasive surgery is not recommended, except for T1A, LVSI-negative tumors, due to a reduction in life expectancy. (3) Locally Advanced Cancer: concurrent chemoradiation (CCRT) followed by brachytherapy (BRT) is the cornerstone treatment. Low-risk patients (fewer than two metastatic nodes or FIGO IB2-II) may consider induction chemotherapy (ICT) followed by CCRT and BRT after 7 days. High-risk patients (two or more metastatic nodes or FIGO IIIA, IIIB, and IVA) benefit from pembrolizumab with CCRT and maintenance therapy. (4) Metastatic, Persistent, and Recurrent Cancer: A PD-L1 status from pretreatment biopsy identifies candidates for Pembrolizumab with available systemic treatment, while triplet therapy (Atezolizumab/Bevacizumab/chemotherapy) becomes a PD-L1-independent option. Conclusions: These evidence-based guidelines aim to improve clinical outcomes through precise treatment strategies based on individual risk factors, predictors, and disease stages.

Spontaneous osteonecrosis of the knee (SONK) is a poorly understood but debilitating disease, that is a common cause of unilateral acute knee pain and swelling. The term \"SONK\" has been replaced by the term \"subchondral insufficiency fracture\" in the latest pathology and imaging literature. Few studies investigated the pathogenesis of SONK by examining the histological changes of the tissues. Very recently, the development of SONK was associated with a meniscal root tear. In terms of the preferred imaging, plain radiographs can confirm the diagnosis in late stages; however, magnetic resonance imaging (MRI) scan is often required. Regarding the treatment, conservative management is usually the treatment of choice in early stages, including a period of non-weightbearing or the use of medications, such as nonsteroidal anti-inflammatory drug (NSAIDS) or bisphosphonates. However, when SONK progresses, often a surgical intervention is required, such as knee replacement, but also minimally invasive techniques, such as arthroscopic intervention, have been described. We present a case of early SONK and discuss the possible pathogenesis of SONK, the clinical presentation, the radiological findings, and we focus on the importance of early diagnosis and early off-load period that is required to prevent further progression of the disease.

Lung cancer remains the leading cause of cancer-related deaths worldwide, mainly due to late diagnosis and the presence of metastases. Several countries around the world have adopted nation-wide LDCT-based lung cancer screening that will benefit patients, shifting the stage at diagnosis to earlier stages with more therapeutic options. Biomarkers can help to optimize the screening process, as well as refine the TNM stratification of lung cancer patients, providing information regarding prognostics and recommending management strategies. Moreover, novel adjuvant strategies will clearly benefit from previous knowledge of the potential aggressiveness and biological traits of a given early-stage surgically resected tumor. This review focuses on proteins as promising biomarkers in the context of lung cancer screening. Despite great efforts, there are still no successful examples of biomarkers in lung cancer that have reached the clinics to be used in early detection and early management. Thus, the field of biomarkers in early lung cancer remains an evident unmet need. A more specific objective of this review is to present an up-to-date technical assessment of the potential use of protein biomarkers in early lung cancer detection and management. We provide an overview regarding the benefits, challenges, pitfalls and constraints in the development process of protein-based biomarkers. Additionally, we examine how a number of emerging protein analytical technologies may contribute to the optimization of novel robust biomarkers for screening and effective management of lung cancer.

OBJECTIVE: Investigating treatment modalities\' association with second primary malignancy risk in early-stage head and neck squamous cell carcinoma (HNSCC).
METHODS: Data of 5-year survivors of early-stage (stages I-II, seventh TNM staging manual) HNSCC from 2000 to 2020 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Standardized incidence ratio and excess absolute risk were used to assess second primary malignancy (SPM) development externally. Relative risk was estimated to compare SPM risk within groups. Fine-Gray\'s model estimated cumulative incidence of second primary malignancy.
RESULTS: Overall, 8957 5-year survivors with early-stage HNSCC were enrolled. Patients receiving definitive radiotherapy had poorer survival than surgery patients. Surgery correlated with lower risk of second primary malignancy (RR = 0.89, 95% CI 0.80-0.99), especially for oropharyngeal squamous cell carcinoma (RR = 0.56, 95% CI 0.39-0.82). Differences in the risk of second primary malignancy among subgroups based on clinical characteristics were not significant. Treatment modalities did not significantly affect risk of second primary malignancy within each subgroup.
CONCLUSIONS: Surgery led to better survival and lower risk of second primary malignancy compared to definitive radiotherapy in 5-year survivors. Incidence and sites of second primary malignancy varied by primary sites, emphasizing targeted long-term surveillance\'s importance.

BACKGROUND: This article is aimed to make predictions in terms of prognostic factors and compare prediction methods by using Cox proportional hazards regression analysis (CPH), some machine learning techniques and Accelerated Failure Time (AFT) model for post-treatment survival probabilities according to clinical presentations and pathological information of early-stage breast cancer patients.
METHODS: The study was carried out in three stages. In the first stage, the CPH method was applied. In the second stage, the AFT model and in the last stage, machine learning methods were applied. The data set consists of 697 breast cancer patients who applied to Marmara University Hospital oncology clinic between 01.01.1994 and 31.12.2009. The models obtained by using various parameters of the patients were compared according to the C index, 5-year survival rate and 10-year survival rate.
CONCLUSIONS: According to the models obtained as a result of the analyses applied, MetLN and age were obtained as a significant risk factor as a result of CPH method and AFT methods, while MetLN, age, tumor size, LV1 and extracapsular involvement were obtained as risk factors in machine learning methods. In addition, when the c-index values of the handheld models are examined, it is obtained as 69.8 for the CPH model, 70.36 for the AFT model, 72.1 for the random survival forest and 72.8 for the gradient boosting machine. In conclusion, the study highlights the potential of comparing conventional statistical methods and machine-learning algorithms to improve the precision of risk factor determination in early-stage breast cancer prognosis. Additionally, efforts should be made to enhance the interpretability of machine-learning models, ensuring that the results obtained can be effectively communicated and utilized by clinical practitioners. This would enable more informed decision-making and personalized care in the treatment and follow-up processes for early-stage breast cancer patients.

BACKGROUND: Early-stage anal squamous cell carcinomas (ASCC) are usually treated with chemoradiotherapy (CRT), with good outcomes. Radiotherapy (RT) alone might be sufficient while reducing toxicity.
METHODS: Patients included in the French prospective FFCD-ANABASE and treated for T1-2N0 ASCC between 2015/01 and 2020/04 were divided into CRT and RT groups. Clinical outcomes and toxicity were reported. Propensity score matching was conducted for 105 pairs of patients.
RESULTS: 440 patients were analyzed: 261 (59.3 %) in the CRT group and 179 (40.7 %) in the RT group. The median follow-up was 35.7 months. Patients receiving CRT were younger, had better Performance Status (PS) and larger tumors. No statistical difference was observed for 3-year Disease-free survival (85.3 % vs 83 %, p = 0.28), Overall survival (89.6 % vs 94.8 %, p = 0.69) and Colostomy-free survival (84.5 % vs 87.2 %, p = 0.84) between CRT and RT groups, respectively. Propensity score-matched analysis confirmed these findings. Treatment interruptions were significantly more frequent in the CRT group (36.3 % vs 21.9 %, p = 0.0013), resulting in an Overall Treatment Time (OTT) extended by 7 days. Grade 3 CTCAE v4.0 toxicities were more prevalent in the CRT group (46 % vs 19 %, p < 0.001).
CONCLUSIONS: Adding chemotherapy to radiotherapy did not significantly improve outcomes for T1-2N0 ASCC in our study, but increased toxicity and OTT.

BACKGROUND: This study compared the survival outcomes after thermal ablation versus wedge resection in patients with stage I non-small cell lung cancer (NSCLC) ≤ 2 cm.
METHODS: Data from the United States (US) National Cancer Institute Surveillance Epidemiology and End Results (SEER) database from 2004 to 2019 were retrospectively analyzed. Patients with stage I NSCLC and lesions ≤ 2 cm who received thermal ablation or wedge resection were included. Patients who received chemotherapy or radiotherapy were excluded. Propensity-score matching (PSM) was applied to balance the baseline characteristics between patients who underwent the two procedures.
RESULTS: Univariate and Cox regression analyses were performed to determine the associations between study variables, overall survival (OS), and cancer-specific survival (CSS). After PSM, 328 patients remained for analysis. Multivariable Cox regression analysis revealed, compared to wedge resection, thermal ablation was significantly associated with a greater risk of poor OS (adjusted HR [aHR]: 1.34, 95% CI: 1.09-1.63, p = 0.004) but not CSS (aHR: 1.28, 95% CI: 0.96-1.71, p = 0.094). In stratified analyses, no significant differences were observed with respect to OS and CSS between the two procedures regardless of histology and grade. In patients with tumor size 1 to 2 cm, compared to wedge resection, thermal ablation was significantly associated with a higher risk of poor OS (aHR: 1.35, 95% CI: 1.10-1.66, p = 0.004). In contrast, no significant difference was found on OS and CSS between thermal ablation and wedge resection among those with tumor size < 1 cm.
CONCLUSIONS: In patients with stage I NSCLC and tumor size < 1 cm, thermal ablation has similar OS and CSS with wedge resection.

UNASSIGNED: Treatments for early laryngeal squamous cell carcinoma (SCC) include radiotherapy (RT), chemoradiotherapy (CRT), and larynx-preserving surgery. In this study, early laryngeal SCC was treated with RT in patients with stage I (T1N0) tumors and with CRT and docetaxel (DOC) in patients with stage II (T2N0) tumors and the treatment results and effectiveness of the chemotherapy were compared.
UNASSIGNED: A total of 78 patients with early-stage laryngeal SCC were enrolled in this study. The T1N0 patients received radiation for the primary lesions as outpatients at a total dose of 63-70 Gy. By contrast, the T2N0 patients were hospitalized and treated with CRT, receiving a total radiation dose of 66-70 Gy. Docetaxel (DOC, 10 mg/m2) was administered intravenously once a week for 6-8 consecutive weeks concurrently with radiotherapy. The adverse events and survival rates with local control rates were examined.
UNASSIGNED: The number of non-glottic T2N0 patients was significantly higher than that of T1N0 patients. Although all patients completed their treatment schedule, significantly more grade 3 adverse events were observed in the T2N0 patients, in particular mucositis and dermatitis, than in T1N0 patients. The 5-year overall survival rate, disease specific survival rate, local control rate, and laryngeal preserve rate of the T1N0 and T2N0 patients were 86.1, 93.3, 88.6, and 94.3% and 85.9, 88.0, 93.1, and 93.1%, respectively.
UNASSIGNED: CRT with docetaxel showed the best therapeutic outcomes for the treatment of laryngeal SCC in patients with T2N0 tumours, with a higher local control rate, effective laryngeal preservation, and relatively few adverse events.

This study aimed to identify the clinical manifestation and implications according to the grading of tumor spread through air spaces in early-stage small (≤2 cm) pathological stage I non-mucinous lung adenocarcinomas. Medical records of patients with pathological stage I tumors sized ≤2 cm were retrospectively reviewed and analyzed. The furthest distance of the spread through air spaces from the tumor margin was measured on a standard-length scale (mm). Enrolled patients were categorized into spread through air spaces (STAS) (-) and STAS (+), and STAS (+) was subdivided according to its furthest distance as follows: STAS (+)-L (<2 mm) and STAS (+)-H (≥2 mm). Risk factors for STAS (+) included papillary predominant subtype (p = 0.027), presence of micropapillary patterns (p < 0.001), and EGFR (p = 0.039). The overall survival of the three groups did not differ significantly (p = 0.565). The recurrence-free survival of STAS (+)-H groups was significantly lower than those of STAS (-) and STAS (+)-L (p < 0.001 and p = 0.039, respectively). A number of alveolar spaces were definite risk factors for STAS (+)-H groups (p < 0.001), and male gender could be one (p = 0.054). In the patient group with small (≤2 cm) pathological stage I lung adenocarcinomas, the presence of STAS ≥ 2 mm was related to significantly lower recurrence-free survival. For identifying definite risk factors for the presence of farther STAS, more precise analysis from a larger study population should be undertaken.

UNASSIGNED: Most patients with breast cancer have early-stage hormone receptor (HR)-positive, human epidermal growth factor receptor-2 (HER2)-negative disease. Even though the prognosis for most of these patients is good, there is a need to identify patients at risk for poor outcomes and to develop strategies to mitigate this risk.
UNASSIGNED: The addition of immunotherapy to standard neoadjuvant chemotherapy represents a promising option for select patients with HR-positive early breast cancer. Three randomized clinical trials have shown favorable results to date. In this review, we discuss the findings of I-SPY2, CheckMate 7FL (NCT04109066), and KEYNOTE-756 (NCT03725059).
UNASSIGNED: Despite the promising results of these trials, there are unanswered questions that need to be considered before incorporating neo/adjuvant immunotherapy in the treatment paradigm of early-stage HR-positive breast cancer. One example of an unanswered question is patient selection. Because the regimens used in these protocols are associated with long-term toxicities, identifying the patients who are more likely to derive a benefit from these agents, such as through the use of biomarkers, is critical. A second example is the optimal integration of adjuvant therapies that improve invasive disease-free survival, such as abemaciclib and ribociclib, which are not safely administered concurrently with immunotherapy.