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Simple Summary: The combination of chemoradiotherapy followed by surgery (trimodality therapy) is considered standard of care for patients with locally advanced esophageal adenocarcinoma, but many potential candidates for surgery receive curative-intent chemoradiotherapy alone. This study compared the outcomes of patients who received trimodality therapy to those who received curative-intent chemoradiotherapy. Our primary analysis found that trimodality therapy reduced the risk of local tumor recurrences, but we did not detect statistically significant differences in the risks of distant metastases or mortality. These results can help patients and clinicians make informed treatment decisions, although further studies are needed to refine our understanding of the trade-offs between the two treatment strategies. The optimal management of patients with locally advanced esophageal adenocarcinoma is unclear. Neoadjuvant chemoradiotherapy followed by esophagectomy (trimodality therapy) is supported as a standard of care, but definitive chemoradiotherapy is frequently given in practice to patients who may have been surgical candidates. This multi-institutional retrospective cohort study compared the outcomes of consecutive patients diagnosed with stage II to IVA esophageal adenocarcinoma between 2004 and 2018 who planned to undergo trimodality therapy or definitive chemoradiotherapy. A total of 493 patients were included, of whom 435 intended to undergo trimodality therapy and 56 intended to undergo definitive chemoradiotherapy. After a median follow-up of 7.3 years, trimodality therapy was associated with a lower risk of locoregional failure (5-year risk, 30.5% vs. 61.3%; HR, 0.39; 95% CI, 0.24–0.62; p < 0.001 ) but not distant metastases (5-year risk, 58.2% vs. 53.9%; HR, 1.21; 95% CI, 0.77–1.91; p = 0.40 ). There were no differences in overall survival (HR, 0.78; 95% CI, 0.56–1.09; p = 0.14 ) or cancer-specific survival (HR, 0.83; 95% CI, 0.57–1.21; p = 0.33 ). Findings were consistent on propensity score-matched sensitivity analyses. In conclusion, trimodality therapy was associated with a lower risk of locoregional failure, but this did not translate into a significantly lower risk of distant failure or improved survival. Further studies are required to accurately estimate the trade-offs between the two treatment strategies. [ABSTRACT FROM AUTHOR]

Simple Summary: The prognosis of metastatic lung cancer has been largely modified with targeted therapies and immunotherapies. Whether this survival benefit for subgroups of patients is beneficial to all patients treated for lung cancer has never been explored. The Institut Curie is an anti-cancer center in Paris, France, treating patients with lung cancer. Since the 2000s, Institut Curie has implemented dematerialized medical records, allowing for a large overview of the survival of patients with lung cancer according to treatment evolution. We found that the survival of patients with metastatic lung cancer has improved over the past 20 years, mostly in NSCLC (non-small cell lung cancer) but not in SCLC (small cell lung cancer). SCLC remains a disease with poor prognosis for which novel therapies are needed. Over the past 20 years, several innovative therapies have been implemented in the treatment of lung cancer that have had reported survival benefits in clinical trials. Whether these improvements translate into the clinic setting has not been studied yet. We retrospectively analyzed all patients consecutively treated at Institute Curie for metastatic lung cancer. Diagnosis date was used to define three periods, based on the approvals of novel treatment strategies in the first-line setting, including targeted therapies in 2010 and immunotherapy in 2018. Endpoints included Overall survival (OS), survival rate of 2 years and 5 years, and a conditional survival rate of 2 years (if still alive at 6 months from treatment initiation). A total of 673 patients were identified for Period 1—2000 to 2009, 752 for Period 2—2010 to 2017, and 768 for Period 3—2018 to 2020. Median OS in the whole cohort was 11.1, 15.5, and 16.2 months, respectively. Median OS for patients with NSCLC or SCLC was 11.2, 17.2, and 18.2 months, or 10.9, 11.7, and 11.2 months, respectively. The two-year conditional survival was more favorable for NSCLC than SCLC patients. Outcomes were statistically higher for women as compared to men in all periods and all subgroups. Survival of patients with metastatic lung cancer has improved over the past 20 years, mostly in NSCLC, along with the implementation of novel treatment strategies. [ABSTRACT FROM AUTHOR]

Simple Summary: Biliary tract cancers, which include cholangiocarcinoma, gallbladder, and ampulla of Vater cancers, are a significant health concern due to their increasing incidence and poor survival rates. Using data from the Rochester Epidemiology Project, this study tracks changes in incidence and survival rates among residents aged 20 and over in Olmsted County, Minnesota from 1976 to 2018. The findings illustrate a rise in overall biliary tract cancers from 6.53 cases to 10.25 cases per 100,000 person-years between 1976 and 2018 (p = 0.004). The incidence of intrahepatic cholangiocarcinoma has significantly increased from 0.25 to 3.93 per 100,000 person-years over the four decades, with a more pronounced increase observed in males, while gallbladder cancer incidence has decreased among women. Despite improvements in median survival times from 4.2 months to 10.8 months over the four decades (p = 0.019), the overall prognosis remains very poor. This study highlights the evolving epidemiology of these cancers and the critical need for enhanced diagnostic and treatment strategies to improve patient outcomes. Biliary tract cancers, including cholangiocarcinoma, gallbladder, and ampulla of Vater cancers, rank second among hepatobiliary cancers, known for their poor prognoses. The United States has witnessed a notable increase in intrahepatic cholangiocarcinoma incidence. This study examines the incidence and survival outcomes of biliary tract cancers in Olmsted County, Minnesota from 1976 to 2018. Using data from the Rochester Epidemiology Project (REP), residents aged 20 and above were analyzed across four eras. Incidence rates were calculated and adjusted for age and sex, and temporal trends were assessed using Poisson regression. Intrahepatic cholangiocarcinoma exhibited a significant escalation in incidence rates over time, while gallbladder cancers showed a decline among women. Median survival times for biliary tract cancers notably improved. These findings confirm the rising incidence of intrahepatic cholangiocarcinoma and suggest improving survival rates. Nevertheless, the overall prognosis for biliary tract cancers remains very poor, emphasizing the continual need for enhanced management strategies and further research. [ABSTRACT FROM AUTHOR]

Simple Summary: The incidence of metastatic melanoma is rising, making it imperative to identify patients who do not benefit from immunotherapy. This study aimed to develop a radiomic biomarker, using segmentations from 146 baseline and 146 first follow-up CT scans, to predict best overall response, progression-free survival, and overall survival across various immunotherapies. We volumetrically segmented the total tumour load, excluding cerebral metastases. This study also examined whether reducing the number of segmented metastases per patient affects predictive accuracy. The findings suggest that delta radiomics could enhance the prediction of best overall response, progression-free survival, and overall survival in metastatic melanoma patients undergoing first-line immunotherapy. Although volumetric whole tumour load segmentation is complex, it may provide predictive benefits. Background: The prevalence of metastatic melanoma is increasing, necessitating the identification of patients who do not benefit from immunotherapy. This study aimed to develop a radiomic biomarker based on the segmentation of all metastases at baseline and the first follow-up CT for the endpoints best overall response (BOR), progression-free survival (PFS), and overall survival (OS), encompassing various immunotherapies. Additionally, this study investigated whether reducing the number of segmented metastases per patient affects predictive capacity. Methods: The total tumour load, excluding cerebral metastases, from 146 baseline and 146 first follow-up CTs of melanoma patients treated with first-line immunotherapy was volumetrically segmented. Twenty-one random forest models were trained and compared for the endpoints BOR; PFS at 6, 9, and 12 months; and OS at 6, 9, and 12 months, using as input either only clinical parameters, whole-tumour-load delta radiomics plus clinical parameters, or delta radiomics from the largest ten metastases plus clinical parameters. Results: The whole-tumour-load delta radiomics model performed best for BOR (AUC 0.81); PFS at 6, 9, and 12 months (AUC 0.82, 0.80, and 0.77); and OS at 6 months (AUC 0.74). The model using delta radiomics from the largest ten metastases performed best for OS at 9 and 12 months (AUC 0.71 and 0.75). Although the radiomic models were numerically superior to the clinical model, statistical significance was not reached. Conclusions: The findings indicate that delta radiomics may offer additional value for predicting BOR, PFS, and OS in metastatic melanoma patients undergoing first-line immunotherapy. Despite its complexity, volumetric whole-tumour-load segmentation could be advantageous. [ABSTRACT FROM AUTHOR]

Simple Summary: Advanced stage laryngeal squamous cell cancer (LSCC) continues to have poor prognosis, with 5-year survival from 50 to 60% and poor functional outcome. PD-L1 and tumor microenvironment (CD4, CD8, CD68 and CD163) expression were investigated in LSCC using immunohistochemistry. PD-L1 expression showed statistically significant positive correlation with all examined tumor microenvironment cells. Higher CD68 and CD163 expression represented significantly worse prognosticators for clinical outcome in patients with LSCC. To find out which LSCC patients will gain from immunomodulation therapies, it is important to understand the relationship between PD-L1 expression, immune cell distribution and prognosis in LSCC patients. Background: Despite the considerable advancement in the field of medicine over recent decades, laryngeal cancer continues to be a challenge. The field of immune oncology has generated promising immunomodulation therapies and opened up new ways of treatment. Methods: Our retrospective study included 102 patients diagnosed with laryngeal squamous cell cancer (LSCC). Immunohistochemistry was used to evaluate the expression of PD-L1 and tumor microenvironment cells (CD4, CD8, CD68 and CD163). Results: PD-L1 expression showed statistically significant positive correlations with all examined tumor microenvironment cells. Patients with high CD68 and CD163 expression intratumorally (p = 0.0005 and p = 0.006, respectively) had statistically significant shorter disease-specific survival. Moreover, a statistically shorter time to recurrence was found in patients with high CD68 intratumoral and CD8 overall counts (p = 0.049 and p = 0.019, respectively). Also, high CD8 overall (>23%) and CD68 intratumoral (>2.7%) expression were statistically significant predictors of recurrence (p = 0.028, OR = 3.11 and p = 0.019, OR = 3.13, respectively). Conclusions: Higher CD68 and CD163 expression represented significantly worse prognosticators for clinical outcomes in patients with LSCC. In order to determine which LSCC patients will benefit from anti-PD-1/PD-L1 inhibitors, it is crucial to elucidate the relationship between PD-L1 expression, immune cell distribution and prognosis in LSCC patients. [ABSTRACT FROM AUTHOR]

Simple Summary: There is ongoing controversy regarding the diagnosis and appropriate treatment of small choroidal melanocytic tumors. Identifying lesions that may evolve into melanomas is crucial due to their metastatic potential. The debate centers on whether it is feasible to delay tumor treatment until signs of progression are evident. This study aims to analyze the long-term outcomes of patients with small choroidal melanocytic tumors under observation, to determine their rate of transformation to melanoma and survival rates in this population. The results suggest that active observation until signs of progression to melanoma appear can be a safe alternative, avoiding the potential side effects of treatment. This approach preserves the visual function and quality of life for patients with tumors that will never progress to melanoma, without compromising their overall prognosis. Background: The purpose of this study is to analyze the long-term evolution of patients with small choroidal melanocytic tumors (SCMTs) undergoing observation, and to assess their rate of transformation into melanomas and survival. Methods: A retrospective single-cohort study of patients with SCMTs (1–3 mm in height and 5–10 mm in base) diagnosed from January 1992 to February 2023 was carried out, with observation as the initial treatment. The main criterion for a transformation into melanoma is considered to be an increase in size of more than 1 mm in height and/or more than 1 mm in base measured on an ultrasound/retinography, recorded in two consecutive visits separated by one to three months. Results: 243 patients were included with a mean age of 65.3 years and a mean follow-up of 7.9 years (6 months–27.9 years); 27 patients showed tumor growth. The probabilities of growth at 5, 10, and 15 years are 10%, 14%, and 17%, respectively. Regarding survival, 22 patients died and only 3 deaths were due to melanoma metastasis. Survival rates at 5 and 10 years are 99% and 97%. Conclusions: Observation is a viable therapeutic option for SCMTs, avoiding the side effects of treatment, considering the majority of these tumors do not progress to melanoma. With close monitoring, patients can be treated promptly upon detecting a transformation. Additionally, the findings confirm that small melanocytic tumors can lead to metastatic disease, albeit at a low rate. [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate cancer is the most common cancer detected among men and it is the second leading cause of death. According to the WHO, cobalt is probably involved in carcinogenesis. However, there are no studies related to cobalt levels and survival in prostate cancer patients. The aim of this prospective study was to investigate the relationship between serum cobalt levels and survival among prostate cancer patients taking into consideration prostate cancer-specific deaths and non-cancer causes of death. Our findings, based on 261 Polish prostate cancer patients, show that individuals with high serum cobalt levels have a significantly worse survival compared to participants with low serum cobalt levels. Prostate cancer is the most common cancer diagnosed in men and the second leading cause of death in male cancer patients. The WHO suggests that cobalt is involved in the carcinogenesis of prostate cancer. There are, however, no studies associating cobalt levels and prostate cancer patient survival. In this study, 261 Polish prostate cancer (n = 261) patients were recruited into a prospective cohort between 2009 and 2015. Serum cobalt levels were measured using ICP-MS after prostate cancer diagnosis and before treatment. All study participants were assigned into quartiles (QI-QIV) based on the distribution of serum cobalt levels among censored patients. Univariable and multivariable COX regression models were used to calculate hazard ratios (HRs) for each serum cobalt level quartile. We found a significant relationship between high serum cobalt levels and poor prostate cancer patient total survival (HR = 2.60; 95% CI: 1.17–5.82; p = 0.02). In relation to prostate cancer patients who died as a result of other non-cancer causes, the association with high levels of cobalt was even stronger (HR = 3.67; 95% CI: 1.03–13.00; p = 0.04). The impact of high serum cobalt levels on overall survival of prostate cancer-specific-related deaths was not statistically significant. [ABSTRACT FROM AUTHOR]

Simple Summary: Given the wide usage of Bevacizumab in current oncological practice, it is very important to compare the "real-world" results to those obtained in controlled clinical trials. This study aims to describe the clinical experience of using Bevacizumab in a large cohort of cancer patients in "non-controlled real-world" conditions regarding effectiveness, safety, and cost of therapy. For this purpose, we conducted an open, observational, retrospective study involving all patients treated for solid malignant tumors in the Bucharest Institute of Oncology with "Prof. Dr. Al. Trestioreanu" with Bevacizumab-based systemic therapy, between 2017 and 2021. Bevacizumab re-mains a high-cost therapy, but it can add to clinical benefits (like overall survival, progression-free survival, and response rate) when used in conjunction with standard chemotherapy. Similar results as those presented in various controlled trials are observable even on unselected cohorts of patients in the uncontrolled conditions of "real-world" oncological practice. Overall, it is estimated that more than 3,500,000 patients have received Bevacizumab as part of systemic oncologic treatment. Bevacizumab and its biosimilars are currently marketed in over 130 countries. Given the wide usage of Bevacizumab in current oncological practice, it is very important to compare the "real-world" results to those obtained in controlled clinical trials. This study aims to describe the clinical experience of using Bevacizumab in a large cohort of cancer patients in "non-controlled real-world" conditions with regard to effectiveness, safety, and cost of therapy. Methods: For this purpose, we conducted an open, observational, retrospective study involving all patients treated for solid malignant tumors in the Bucharest Institute of Oncology with "Prof. Dr. Al. Trestioreanu" with Bevacizumab-based systemic therapy, between 2017 and 2021. Results: The study consisted of 657 treatment episodes in 625 patients (F/B = 1.62/1, with a median age of 57.6 years) which were treated for malignant tumors (majority colorectal, non-small cell lung, ovarian, and breast cancer). First-line treatment was administered in 229 patients, and the rest received Bevacizumab as second or subsequent lines of treatment. The overall response rate to Bevacizumab-based therapies was around 60–65% across all indication except for subsequent treatment lines in colorectal and ovarian cancers, where lower values were recorded (27.1%, and 31.5% respectively). Median PFS for the entire cohort was 8.2 months (95% CI 6.8–9.6), and the median OS was 13.2 months (95% CI 11.5–14.9). Usual bevacizumab-related toxicities were observed, including bleeding, hypertension, wound-healing complications, gastrointestinal perforation, other types of fistulas, septic complications, and thromboembolic events. Although the clinical benefits are undeniable, the addition of Bevacizumab to standard chemotherapy increased the overall treatment cost by 213%. Conclusions: Bevacizumab remains a high-cost therapy, but it can add to clinical benefits (like overall survival, progression-free survival, and response rate) when used in conjunction with standard chemotherapy. Similar results as those presented in various controlled trials are observable even on unselected cohorts of patients in the uncontrolled conditions of "real-world" oncological practice. Off-label usage is encountered in clinical practice, and this aspect should be monitored given the potential adverse effects of the therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: This study focused on the trends of Head and Neck Cancers (HNC) in the First Nations people of Australia. There is an underwhelming amount of literature holistically analysing the trend of HNC among the First Nations people. This study comprehensively analysed incidence, mortality, and survival rates in the First Nations people, and compared these trends with the non-Indigenous Australian population. This emphasized the need to investigate the underlying causes and barriers for differences in the HNC burden between First Nations people and non-Indigenous Australians. Collaborative efforts, spanning from local to national levels, are required to address the HNC burden in Australia, particularly, in First Nations communities. Background: We aim to assess and compare the HNC trends between the First Nations and non-Indigenous population. Methods: HNC incidence (1998–2013) and mortality (1998–2015) data in First Nations people and non-Indigenous Australians were utilised from the Australian Cancer Database. The age-standardised incidence and mortality trends along with annual percentage changes were analysed using Joinpoint models. Age-standardised incidence and mortality rates according to remoteness, states, and five-year survival rates among First Nations people and non-Indigenous Australians were presented as graphs. Results: First Nations people had over twice the age-standardised incidence (2013; 29.8/100,000 vs. 14.7/100,000) and over 3.5 times the age-standardised mortality rates (2015; 14.2/100,000 vs. 4.1/100,000) than their non-Indigenous counterparts. Both populations saw a decline in mortality, but the decline was only statistically significant in non-Indigenous Australians (17.1% decline, 1998: 4.8/100,000, 2015: 4.1/100,000; p < 0.05). Across all remoteness levels and states, First Nations people consistently had higher age-standardised incidence and mortality rates. Furthermore, the five-year survival rate was lower by 25% in First Nations people. Conclusion: First Nations people continue to shoulder a disproportionate HNC burden compared to non-Indigenous Australians. [ABSTRACT FROM AUTHOR]

Simple Summary: Perineural invasion (PNI) is the infiltration of cancer cells into peripheral nerves and is recognized as potential cancer metastasis. The presence of PNI has been extensively studied as a prognostic factor in head and neck squamous cell carcinoma (HNSCC) recently. The aim of this study was to quantitatively assess the prognostic value of PNI in HNSCC. From the results of the systematic review and meta-analysis, we confirmed that PNI is an independent prognostic factor in HNSCC. Specifically, HNSCC patients with PNI have worse survival, and are more likely to relapse locally, regionally, and distantly compared to those without PNI. We hope that these findings can serve as a basis for consideration of PNI as an indicator for more advanced pathological stages and more intensive clinical management for HNSCC patients. The aim of this study was to conduct a comprehensive review of the predictive significance of PNI in HNSCC survival outcomes. A systematic search was conducted across multiple databases, and all studies published in the last decade were screened (Research Registry ID: reviewregistry1853). The included studies were assessed using the Quality in Prognosis Studies tool. Survival outcome data were extracted, combined, and presented as hazard ratios (HR) with a 95% confidence interval (CI). Totally, 74 studies encompassing 27,559 patients were analyzed and revealed a cumulative occurrent rate of 30% for PNI in HNSCC. PNI+ HNSCC patients had a worse overall survival (HR: 1.91, 95% CI: 1.71–2.13), disease-specific survival (HR: 1.79, 95% CI: 1.55–2.07), disease-free survival (HR: 1.82, 95% CI: 1.69–1.96), local recurrence (HR: 2.54, 95% CI: 1.93–3.33), locoregional recurrence (HR: 2.27, 95% CI: 1.82–2.82), locoregional relapse free survival (HR: 1.77, 95% CI: 1.28–2.45), distant metastasis (HR: 1.82, 95% CI: 1.34–2.48), and distant metastasis-free survival (HR: 2.97, 95% CI: 1.82–4.85) compared to those PNI– patients. The available evidence unequivocally establishes PNI as a critical prognostic factor for worse survival in HNSCC patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Certain genetic changes, called driver mutations, can affect how uveal melanoma progresses and spreads. We reviewed and combined data from 13 studies to better understand these effects. A mutation in the BAP1 gene significantly increases the risk of metastatic disease. Other mutations in GNAQ, GNA11, or SF3B1 did not show a similar risk. The prognosis of uveal melanoma is significantly influenced by the risk of metastasis, which varies according to clinical and genetic features. Driver mutations can predict the likelihood of disease progression and survival, although the data in the literature are inconsistent. This meta-analysis aimed to evaluate the prognostic significance of driver mutations, including GNAQ, GNA11, BAP1, and SF3B1, in the advancement of uveal melanoma. A comprehensive search of databases yielded relevant studies, and data from 13 studies (848 eyes) were synthesized to assess the impact of these mutations on metastasis-free survival. The BAP1 mutation and negative immunohistochemistry were associated with a higher risk of metastasis (logHR = 1.44, 95% CI 1.05–1.83). GNAQ, GNA11, and SF3B1 mutations did not show a significant increase in risk. In summary, BAP1 has proven to reliably predict the likelihood of disease progression in uveal melanoma, while further studies are needed to establish the significance of other driver mutations. [ABSTRACT FROM AUTHOR]

Simple Summary: Thymic neuroendocrine tumors (Th-NETs) are rare, with limited research on prognostic markers and treatments. Our retrospective study evaluated clinicopathological characteristics and therapeutic strategies for Th-NETs, filling gaps in existing studies. We highlighted the importance of biomarkers such as serum neuron-specific enolase, inflammatory factors, and oxygen 6-methylguanine-DNA methyltransferase, as well as the roles of surgical interventions, postoperative therapies, and temozolomide-based chemotherapy in improving patient survival. Our findings confirmed the crucial role of surgical treatment and the potential benefits of postoperative adjuvant radiotherapy. Furthermore, temozolomide-based chemotherapy demonstrated efficacy in Th-NETs treatment, with the neutrophil-to-lymphocyte ratio and serum neuron-specific enolase proving to be valuable prognostic markers necessitating further research. Background: Thymic neuroendocrine tumors (Th-NETs) are rare and aggressive, with a scarcity of research on predicting patient prognosis. Our study aimed to assess the impact of prognostic markers and temozolomide (TMZ)-based chemotherapy on survival in Th-NETs. Methods: We retrospectively reviewed the medical records of patients diagnosed with Th-NETs between 2013 and 2023 at our institution. We collected clinicopathological data, including tumor pathological grading, staging, serum concentrations of neuron-specific enolase (NSE) and pro-gastrin-releasing peptide, levels of inflammatory factors, and expression of oxygen 6-methylguanine-DNA methyltransferase (MGMT). Treatment details (such as surgery and chemotherapy) and survival outcomes were also documented. Results: A total of 32 patients were included in our study after excluding those without complete available information. The median progression-free survival (PFS) was 12.5 months (95%CI, 8–16 months) for 19 patients who received TMZ-based chemotherapy. Twenty-one patients underwent surgery as the primary treatment, demonstrating a median disease-free survival (DFS) of 51.0 months. The inflammatory factor neutrophil-to-lymphocyte ratio (NLR) was an independent prognostic indicator of DFS in postoperative patients and PFS in TMZ-treated patients. The overall 3-, 5-, and 10-year survival rates were 86.6%, 69.5%, and 33.8%, respectively. Ki67 level exceeding 10% (p = 0.048) and absence of surgical resection (p = 0.003) were significantly associated with worse overall survival (OS). Conclusion: Surgical treatment was currently the primary method for treating Th-NETs, and postoperative adjuvant therapy was an essential consideration for specific patient cohorts. Despite widespread positive MGMT expression, TMZ-based chemotherapy showed promise. Some potential prognostic biomarkers such as NLR and NSE need more attention. [ABSTRACT FROM AUTHOR]

Simple Summary: This study is an analytic review of the data on the two most used ALK TKIs, alectinib and lorlatinib, used as the first treatment for ALK-positive NSCLC. These drugs have shown promise in separate studies, but there has not been a direct comparison until now. We analyzed data from two major clinical trials that compared these drugs to crizotinib. We found that lorlatinib may be more effective in delaying the progression of the disease compared to alectinib, especially in controlling brain metastases. Although both drugs have side effects, and an alert has been created for the peculiar toxicities of lorlatinib, more people had to stop taking alectinib due to side effects compared to lorlatinib. Overall, the data suggest that lorlatinib might be a better option for patients with this type of lung cancer, but more research is needed to confirm these findings. This information could help clinicians make better treatment decisions for patients with ALK-positive NSCLC. Various next-generation ALK TKIs are available as first-line options for ALK-positive NSCLC, with alectinib and lorlatinib being commonly preferred. However, no direct comparison between them has been conducted, making it impossible to pick a winner. We performed an analytic, 'non-comparative' assessment of the two phase 3 pivotal clinical trials showing superiority of alectinib (ALEX) and lorlatinib (CROWN) in comparison to crizotinib. Overall, the two studies were very similar in the study design and patient characteristics, with the exception of the selection and evaluation of brain metastases. PFS hazard ratios numerically favored lorlatinib, both according to the investigator and to BICR. Notably, the 3-year PFS rate was numerically higher with lorlatinib (64%) than with alectinib (46.4%). Despite similar response rates and overall intracranial response, the rate of complete intracranial response was higher with lorlatinib, with a cumulative incidence risk of CNS disease progression at 12 months of 9.4% with alectinib and 2.8% with lorlatinib. The peculiar toxicities of lorlatinib were related to lipidic profile alterations, peripheral oedema and cognitive effects, with no impact on cardiovascular risk nor impairment in quality of life versus crizotinib. Furthermore, the rate of permanent treatment discontinuation due to adverse events was numerically higher with alectinib (26%) than with lorlatinib (7%). In conclusion, despite the immature OS data for both drugs, the efficacy of lorlatinib appears higher than alectinib while maintaining a manageable toxicity profile. [ABSTRACT FROM AUTHOR]

Simple Summary: Neoadjuvant chemotherapy in breast cancer facilitates breast and axillary surgery and offers significant prognostic value. We present a retrospective cohort of 482 stage II and III breast cancer patients treated with neoadjuvant chemotherapy based on anthracycline and taxans, plus antiHER2 in HER2-positive cases. The 10-year estimated disease free survival was 77.3% (95%CI 73.3–81.4%) and the Breast cancer specific survival 83.7% (95%CI 80.3–87.2%). The statistically independent factors related to patient survival were pathology subtype (lobular cancers HR, 4); molecular surrogate subtype (triple negative HR, 4); type of surgery (mastectomy HR, 2), response to chemotherapy (the risk incremented according to the residual cancer burden in 2.2, 4.4 and 8.0 times in I, II and III, respectively) and vascular invasion (HR, 2.4). BRCA carriers presented a longer survival, with an estimated 10 years DDFS of 89.6% vs. 77.2% for non-carriers, p = 0.054. Long-term outcomes after neoadjuvant chemotherapy can help patients and clinicians make well-informed decisions. Introduction: Neoadjuvant chemotherapy in breast cancer offers the possibility to facilitate breast and axillary surgery; it is a test of chemosensibility in vivo with significant prognostic value and may be used to tailor adjuvant treatment according to the response. Material and Methods: A retrospective single-institution cohort of 482 stage II and III breast cancer patients treated with neoadjuvant chemotherapy based on anthracycline and taxans, plus antiHEr2 in Her2-positive cases, was studied. Survival was calculated at 5 and 10 years. Kaplan–Meier curves with a log-rank test were calculated for differences according to age, BRCA status, menopausal status, TNM, pathological and molecular surrogate subtype, 20% TIL cut-off, surgical procedure, response to chemotherapy and the presence of vascular invasion. Results: The pCR rate was 25.3% and was greater in HER2 (51.3%) and TNBC (31.7%) and in BRCA carriers (41.9%). The factors independently related to patient survival were pathology and molecular surrogate subtype, type of surgery, response to NACT and vascular invasion. BRCA status was a protective prognostic factor without reaching statistical significance, with an HR 0.5 (95%CI 0.1–1.4). Mastectomy presented a double risk of distant recurrence compared to breast-conservative surgery (BCS), supporting BCS as a safe option after NACT. After a mean follow-up of 126 (SD 43) months, luminal tumors presented a substantial difference in survival rates calculated at 5 or 10 years (81.2% compared to 74.7%), whereas that for TNBC was 75.3 and 73.5, respectively. The greatest difference was seen according to the response in patients with pCR, who exhibited a 10 years DDFS of 95.5% vs. 72.4% for those patients without pCR, p < 0001. This difference was especially meaningful in TNBC: the 10 years DDFS according to an RCB of 0 to 3 was 100%, 80.6%, 69% and 49.2%, respectively, p < 0001. Patients with a particularly poor prognosis were those with lobular carcinomas, with a 10 years DDFS of 42.9% vs. 79.7% for ductal carcinomas, p = 0.001, and patients with vascular invasion at the surgical specimen, with a 10 years DDFS of 59.2% vs. 83.6% for those patients without vascular invasion, p < 0.001. Remarkably, BRCA carriers presented a longer survival, with an estimated 10 years DDFS of 89.6% vs. 77.2% for non-carriers, p = 0.054. Conclusions: Long-term outcomes after neoadjuvant chemotherapy can help patients and clinicians make well-informed decisions. [ABSTRACT FROM AUTHOR]

Simple Summary: Lung cancer remains a leading cause of cancer-related mortality globally, requiring new diagnostic and therapeutic approaches. This research arises from the need to improve diagnostic accuracy and treatment effectiveness for patients with non-small cell lung cancer. The authors aim to systematically evaluate the potential of emerging biomarkers, including circulating tumor DNA, microRNAs and mutational load of blood tumors and their relationship with different treatments. The findings of this study could have a significant impact on the research community by providing a basis for integrating these biomarkers into clinical practice, thereby improving personalized treatment strategies and patient outcomes in non-small cell lung cancer. Non-small-cell lung cancer (NSCLC) comprises approximately 85% of all lung cancer cases, often diagnosed at advanced stages, which diminishes the effective treatment options and survival rates. This systematic review assesses the utility of emerging biomarkers—circulating tumor DNA (ctDNA), microRNAs (miRNAs), and the blood tumor mutational burden (bTMB)—enhanced by next-generation sequencing (NGS) to improve the diagnostic accuracy, prognostic evaluation, and treatment strategies in NSCLC. Analyzing data from 37 studies involving 10,332 patients from 2020 to 2024, the review highlights how biomarkers like ctDNA and PD-L1 expression critically inform the selection of personalized therapies, particularly beneficial in the advanced stages of NSCLC. These biomarkers are critical for prognostic assessments and in dynamically adapting treatment plans, where high PD-L1 expression and specific genetic mutations (e.g., ALK fusions, EGFR mutations) significantly guide the use of targeted therapies and immunotherapies. The findings recommend integrating these biomarkers into standardized clinical pathways to maximize their potential in enhancing the treatment precision, ultimately fostering significant advancements in oncology and improving patient outcomes and quality of life. This review substantiates the prognostic and predictive value of these biomarkers and emphasizes the need for ongoing innovation in biomarker research. [ABSTRACT FROM AUTHOR]

Simple Summary: Identification of germline pathogenic variants in breast cancer patients holds significant importance for accurate risk assessment and therapeutic interventions. However, research focusing on very young breast cancer patients remains limited. Our objective was to describe the prevalence, gene, and variant spectra alongside clinicopathological characteristics and outcomes of women diagnosed with breast cancer ≤30 years. Our observations revealed that one in three patients carried predisposing variants distributed in eight established breast cancer genes. Predominantly, causative variants implicated loss-of-function of BRCA1, TP53, and BRCA2, with TP53 emerging as the second most frequently mutated gene within this cohort. While carrier status did not impact event-free survival, carriers who underwent neoadjuvant chemotherapy exhibited improved prognostic outcomes. Our data underscore the substantial proportion of patients with hereditary predisposition, advocate for the inclusion of TP53 genetic testing, and suggest possible benefits of neoadjuvant chemotherapy in this very young group of breast cancer patients. Early-onset breast cancer constitutes a major criterion for genetic testing referral. Nevertheless, studies focusing on breast cancer patients (≤30 years) are limited. We investigated the contribution and spectrum of known breast-cancer-associated genes in 267 Greek women with breast cancer ≤30 years while monitoring their clinicopathological characteristics and outcomes. In this cohort, a significant proportion (39.7%) carried germline pathogenic variants (PVs) distributed in 8 genes. The majority, namely 36.7%, involved BRCA1, TP53, and BRCA2. PVs in BRCA1 were the most prevalent (28.1%), followed by TP53 (4.5%) and BRCA2 (4.1%) PVs. The contribution of PVs in CHEK2, ATM, PALB2, PTEN, and RAD51C was limited to 3%. In the patient group ≤26 years, TP53 PVs were significantly higher compared to the group 26–30 years (p = 0.0023). A total of 74.8% of TP53 carriers did not report a family history of cancer. Carriers of PVs receiving neoadjuvant chemotherapy showed an improved event-free survival (p < 0.0001) compared to non-carriers. Overall, many women with early-onset breast cancer carry clinically actionable variants, mainly in the BRCA1/2 and TP53 genes. The inclusion of timely testing of TP53 in these patients provides essential information for appropriate clinical management. This is important for countries where reimbursement involves the cost of genetic analysis of BRCA1/2 only. [ABSTRACT FROM AUTHOR]

Simple Summary: This study of nonsquamous lung cancer patients undergoing neoadjuvant chemotherapy with bevacizumab followed by surgery revealed that 20% were pathologic responders, experiencing 100% 5-year survival rates. In contrast, the 80% nonresponders demonstrated significantly lower rates. Pathologic response emerged as a survival predictor, indicating prolonged post-surgery survival for responders, while nonresponders required additional therapy for improved outcomes. The objective of this study was to evaluate the relationship between pathologic response and survival in patients with clinical stage II/IIIA nonsquamous non-small-cell lung cancer (NSCLC) who intended to undergo neoadjuvant chemotherapy with bevacizumab, followed by surgery. In this phase II NAVAL study evaluating the feasibility of neoadjuvant chemotherapy with cisplatin (75 mg/m2), pemetrexed (500 mg/m2), and bevacizumab (15 mg/kg), followed by surgery, progression-free survival (PFS) and overall survival (OS) were assessed as the secondary endpoints. Patients were categorized based on the proportion of residual viable primary tumor in the resected specimen after neoadjuvant chemotherapy: those with residual tumor in less than one-third were classified as pathologic responders, the rest as nonresponders. Of the 30 patients, 25 underwent surgical resection after three cycles of neoadjuvant chemotherapy with bevacizumab; 5 did not undergo surgery. Among all 30 patients, the rates of 2- and 5-year PFS were 41.5% and 34.6%, respectively, and the rates of 2- and 5-year OS were 70.0% and 60.0%, respectively. A total of 6 patients (20%) were classified as pathologic responders; the other 24 (80%), as nonresponders. The five-year PFS differed significantly between pathologic responders (100%) and nonresponders (17.5%; p = 0.002). The five-year OS also differed significantly between pathologic responders (100%) and nonresponders (43.5%; p = 0.006). Pathologic response seems to be a predictor of survival. Long-term survival after surgery is expected for pathologic responders, whereas additional therapy is needed for nonresponders. [ABSTRACT FROM AUTHOR]

Simple Summary: Sorafenib has been the standard of care for advanced hepatocellular carcinoma (aHCC) patients since 2008. Recently, new therapies have been funded that provide increased survival in this patient population. The aim of our retrospective cohort study of linked administrative databases in Ontario was to understand the characteristics of patients with aHCC, their treatment patterns, survival outcomes, healthcare resource utilization (HCRU), and costs. We observed that patients who received systemic therapy for aHCC had a higher median overall survival (mOS) from diagnosis compared to patients who received other systemic therapies or a locoregional treatment (LRT). The mean cost per patient was $52,166 CAD for all the patients in the study, with inpatient hospitalizations and oral medications as the largest cost drivers. The therapeutic landscape for aHCC has evolved in recent years, necessitating a comprehensive analysis of treatment patterns, clinical outcomes, HCRU, and costs to contextualize emerging treatments. This study aimed to investigate these outcomes using real-world data from Ontario, Canada. This retrospective cohort study was conducted using linked administrative databases from April 2010 to March 2020. Patients diagnosed with aHCC were included, and their clinical and demographic characteristics were analyzed, as well as treatment patterns, survival, HCRU, and economic burden. Among 7322 identified patients, 802 aHCC patients met the eligibility criteria for inclusion in the study. Treatment subgroups included 1L systemic therapy (53.2%), other systemic treatments (4.5%), LRT (9.0%), and no treatment (33.3%). The median age was 66 years, and the majority were male (82%). The mOS for the entire cohort from diagnosis was 6.5 months. However, patients who received 1L systemic therapy had an mOS of 9.0 months, which was significantly higher than the other three subgroups. The mean cost per aHCC-treated patient was $49,640 CAD, with oral medications and inpatient hospitalizations as the largest cost drivers. The results underscore the need for the continuous evaluation and optimization of HCC management strategies in the era of evolving therapeutic options. [ABSTRACT FROM AUTHOR]

Simple Summary: The current options for second-line therapy in unresectable liver cancer are limited, with an evolving role for immunotherapeutic regimens. This study examines the role of nivolumab as a second-line treatment option in 42 patients with liver cancer who had failed first-line therapy with sorafenib and compared outcomes in another 38 patients who were maintained on sorafenib therapy. Our results show that nivolumab prolongs survival in such patients compared to those who were continued on sorafenib therapy. This study adds to the growing body of research that nivolumab may be an effective treatment option in patients with unresectable and advanced liver cancer. Background: Limited data exists for the efficacy and outcomes of nivolumab as a second-line treatment for unresectable hepatocellular carcinoma (uHCC). We aimed to assess the efficacy and safety of nivolumab in patients with uHCC who experienced disease progression during sorafenib treatment. Methods: In this retrospective, observational, multicenter study, adult Child-Turcotte-Pugh A/7B patients with uHCC who tolerated sorafenib therapy but showed disease progression switched to second-line intravenous nivolumab (n = 42). A similar number of consecutive, unselected patients who were maintained on sorafenib therapy, regardless of tumoral response or progression, served as historical controls (n = 38). The primary endpoint was overall survival (OS, defined as the time from starting sorafenib in either group up to death due to any cause) and analyzed by intention-to-treat. Results: The mean age of the overall cohort was 72.4 ± 10.1 years, of whom 87.5% were males and 58.8% had underlying viral etiology. Patients in the two cohorts were similar, except those who received nivolumab had more co-morbidities (70.0% vs. 15.4%), ECOG-2 status (21.4% vs. 15.8%), BCLC stage C (81.0% vs. 47.4%), and extravascular invasion (54.4% vs. 21.8%) (p < 0.05 for all). More patients in the nivolumab arm were Child-Turcotte-Pugh B (35.7% vs. 21.1%, p = 0.15). Median OS was 22.2 months (95% CI: 8.9–49.8) on second-line nivolumab and 11.0 months (95% CI: 3.6–18.4) on sorafenib alone (HR 1.93; 95% CI: 1.1–3.3, p = 0.014). Median OS after starting nivolumab was 10.2 months, and time-to-progression was 4.9 months (95% CI: 3.2–6.3). Conclusion: Nivolumab is an effective second-line treatment option in patients with uHCC who progress on sorafenib, with significantly improved OS. These early real-life data offer encouraging results, similar to those shown in Phase I/IIa clinical trials. Further investigations are warranted for the use of nivolumab as a monotherapy. [ABSTRACT FROM AUTHOR]

Simple Summary: For patients with solid tumor brain metastases that progress after whole-brain radiotherapy, there are limited treatment options. The aim of our prospective trial was to examine the usage of bevacizumab as salvage therapy in this specific patient population, with primary endpoints being radiologic response, survival, safety, and quality of life. Our data show that bevacizumab was well tolerated, maintained quality of life, and improved overall survival with radiologic response. Patients with solid tumor brain metastases that progress after whole-brain radiation have limited options. This prospective trial investigated the efficacy, safety, and tolerability of bevacizumab as salvage therapy in this population. Eligible patients received bevacizumab 10 mg/kg intravenously every 2 weeks until progression. The primary endpoint was radiologic response using Response Assessment in Neuro-Oncology (RANO) criteria. The secondary endpoints were progression-free survival (PFS), overall survival (OS), duration of response, and safety. Quality of life (QOL) was studied using the Functional Assessment of Cancer Therapy-Brain (FACT-Br) scale. Twenty-seven patients were enrolled, with twenty-four having evaluable data for response. The majority of histologies (n = 21, 78%) were breast cancer. The remaining histologies were non-small-cell lung cancer (n = 4, 15%), neuroendocrine cancer (n = 1, 3%), and papillary fallopian serous adenocarcinoma (n = 1, 3%). Eighteen patients had radiologic response, with two patients demonstrating partial response (8.33%) and sixteen patients demonstrating stable disease (66.7%). The median duration of response was 203 days. PFS at 6 months was 46%, median PFS was 5.3 m, and median OS was 9.5 m. Treatment was well tolerated, with six patients experiencing grade 3 lymphopenia and hypertension. There was one grade 3 thromboembolism. QOL was not negatively impacted. Bevacizumab is a safe and feasible salvage treatment with durable response and favorable overall survival for patients with progressive brain metastases after whole-brain radiation. [ABSTRACT FROM AUTHOR]

Simple Summary: Stereotactic body radiotherapy (SBRT) is a highly precise, non-invasive, and image-guided form of hypofractionated radiotherapy aimed at well-defined small targets. It is characterized by superior conformity of dose distribution, steep dose drop-off gradients, and short overall treatment time, which allow effective protection of surrounding normal tissue from high radiation doses, potentially resulting in lower toxicity and a more potent biological effect. Currently, SBRT is an established curative therapy for certain cancers and some benign tumors, as well as a valuable palliative option. There is limited experience with SBRT for de novo mucosal carcinoma of the head and neck. A systematic review of the literature and subsequent analysis of 124 patients from five studies treated between 2012 and 2020 confirmed that SBRT is an effective and relatively safe treatment for small tumor targets in de novo mucosal carcinoma of the head and neck. Standardization of SBRT practice and well-designed prospective clinical trials are highly needed. Stereotactic body radiotherapy (SBRT) is characterized by a high dose per fraction, well-defined small targets, superior dose conformity, and a steep off-target dose gradient. A literature search was conducted to examine the experience with SBRT as a curative treatment for newly diagnosed mucosal carcinoma of the head and neck (MCHN). Four retrospective case series and one prospective phase I clinical trial published between 2012 and 2020 described 124 patients. SBRT was mainly performed in older patients with different tumor sites. The median size of the planning target volumes ranged from 5.3 to 41 cm3. Different approaches were used to create margins. In two studies, limited elective nodal irradiation was performed. The equivalent doses used were 60–83.33 Gy delivered in five fractions. Considerable heterogeneity was observed in the radiation dose specification. The incidence of grade ≥3 late toxicity was 0–8.3%, with local and regional control ranging from 73% to 100%. Improved or stable quality of life after SBRT was reported in two studies. Curative-intent SBRT for de novo MCHN appears to be an effective and relatively safe treatment for small tumor targets, preferably without concomitant elective tissue irradiation. Standardization of SBRT practice and well-designed prospective clinical trials are needed to better define the role of SBRT in this setting. [ABSTRACT FROM AUTHOR]

Simple Summary: The epidemiology of primary liver cancer is changing according to effective primary prevention interventions, a strictly clinical follow up of chronic patients with hepatitis and successful drug treatments of virus-related liver diseases. A reduction in virus-related hepatocellular carcinomas cases was followed by an increase in the non-viral aetiology, including metabolic and cryptogenetic factors. We used cancer surveillance data to investigate determinants potentially associated with primary liver cancer survival in a southern Italian setting characterised by a high prevalence of hepatitis viral infections and overweight and obesity. Our study provided some new insights into the potential relationship between deprivation, geographic location, access to care and hepatocarcinoma survival. Comprehensive national and regional health plans should consider the evidence provided to ensure equitable access to prevention and care pathways. While entering the digital prevention era, interoperating cancer registries with other sources providing data on lifestyles and health determinants should be promoted. A retrospective observational study utilising cancer incidence data from a population-based registry investigated determinants affecting primary liver cancer survival in a southern Italian region with high hepatitis viral infection rates and obesity prevalence. Among 2687 patients diagnosed between 2006 and 2019 (65.3% male), a flexible hazard-based regression model revealed factors influencing 5-year survival rates. High deprivation levels [HR = 1.41 (95%CI = 1.15–1.76); p < 0.001], poor access to care [HR = 1.99 (95%IC = 1.70–2.35); p < 0.0001], age between 65 and 75 [HR = 1.48 (95%IC = 1.09–2.01); p < 0.05] or >75 [HR = 2.21 (95%CI = 1.62–3.01); p < 0.0001] and residing in non-urban areas [HR = 1.35 (95%CI = 1.08–1.69); p < 0.01] were associated with poorer survival estimates. While deprivation appeared to be a risk factor for primary liver cancer patients residing within the urban area, the geographic distance from specialised treatment centres emerged as a potential determinant of lower survival estimates for residents in the non-urban areas. After balancing the groups of easy and poor access to care using a propensity score approach, poor access to care and a lower socioeconomic status resulted in potentially having a negative impact on primary liver cancer survival, particularly among urban residents. We emphasise the need to interoperate cancer registries with other data sources and to deploy innovative digital solutions to improve cancer prevention. [ABSTRACT FROM AUTHOR]

Simple Summary: Hereditary breast cancer represents a significant proportion of breast cancer cases worldwide, and BRCA1 and BRCA2 explain the majority of these. Less frequent genes with variable penetrance remain less characterized in Colombia. This study explores the characteristics and outcomes of 82 breast cancer patients with germline pathogenic/likely pathogenic variants (PVs) treated and followed at the Instituto Nacional de Cancerología, Colombia (INC-C) from 2018 to 2021 as part of an Institutional Hereditary Cancer Program implementation. We described the distribution of germline PVs among the different breast cancer molecular subtypes in this cohort of carriers. We observed that most PVs were in known breast cancer susceptibility genes, and PVs in BRCA2 were the most frequent. Notably, we observed that patients with disease progression were predominantly carriers of PVs in the BRCA2 gene. This study aimed to investigate prognosis and survival differences in 82 breast cancer patients with germline pathogenic/likely pathogenic variants (PVs) treated and followed at the Breast Unit of the Instituto Nacional de Cancerología, Colombia (INC-C) between 2018 and 2021. Median age at diagnosis was 46 years, with 62.2% presenting locally advanced tumors, 47.6% histological grade 3, and 35.4% with triple-negative breast cancer (TNBC) subtype. Most carriers, 74.4% (61/82), had PVs in known breast cancer susceptibility genes (i.e., "associated gene carriers" group, considered inherited breast cancer cases): BRCA2 (30), BRCA1 (14), BARD1 (4), RAD51D (3), TP53 (2), PALB2 (2), ATM (2), CHEK2 (1), RAD51C (1), NF1 (1), and PTEN (1). BRCA1-2 represented 53.7%, and homologous recombination DNA damage repair (HR-DDR) genes associated with breast cancer risk accounted for 15.9%. Patients with PVs in non-breast-cancer risk genes were combined in a different category (21/82; 25.6%) (i.e., "non-associated gene carriers" group, considered other breast cancer cases). Median follow-up was 38.1 months, and 24% experienced recurrence, with 90% being distant. The 5-year Disease-Free Survival (DFS) for inherited breast cancer cases was 66.5%, and for other breast cancer cases it was 88.2%. In particular, for carriers of PVs in the BRCA2 gene, it was 37.6%. The 5-year Overall Survival (OS) rates ranged from 68.8% for those with PVs in BRCA2 to 100% for those with PVs in other HR-DDR genes. Further studies are crucial for understanding tumor behavior and therapy response differences among Colombian breast cancer patients with germline PVs. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aimed to identify and validate genes specific for the survival of patients with papillary renal cell carcinoma (PRCC) in the TCGA-KIRP and Korean-KIRP databases. Using machine learning with statistical analysis, 40 survival-specific genes were identified in TCGA-KIRP. Of them, 10 were verified as survival-specific genes for Korean-KIRP patients through next-generation sequencing. Among these, BAP1, PCSK2, and SPATA13 showed significant survival specificity in both overall survival and disease-free survival. Survival gene signatures, including PCSK2, which are commonly obtained from 40 gene signatures in TCGA and 10 gene signatures in Korean databases, are expected to provide insight into predicting the survival of PRCC patients and developing new treatments. Purpose: Papillary renal cell carcinoma (PRCC), the second most common kidney cancer, is morphologically, genetically, and molecularly heterogeneous with diverse clinical manifestations. Genetic variations of PRCC and their association with survival are not yet well-understood. This study aimed to identify and validate survival-specific genes in PRCC and explore their clinical utility. Materials and Methods: Using machine learning, 293 patients from the Cancer Genome Atlas-Kidney Renal Papillary Cell Carcinoma (TCGA-KIRP) database were analyzed to derive genes associated with survival. To validate these genes, DNAs were extracted from the tissues of 60 Korean PRCC patients. Next generation sequencing was conducted using a customized PRCC gene panel of 202 genes, including 171 survival-specific genes. Kaplan–Meier and Log-rank tests were used for survival analysis. Fisher's exact test was performed to assess the clinical utility of variant genes. Results: A total of 40 survival-specific genes were identified in the TCGA-KIRP database through machine learning and statistical analysis. Of them, 10 (BAP1, BRAF, CFDP1, EGFR, ITM2B, JAK1, NODAL, PCSK2, SPATA13, and SYT5) were validated in the Korean-KIRP database. Among these survival gene signatures, three genes (BAP1, PCSK2, and SPATA13) showed survival specificity in both overall survival (OS) (p = 0.00004, p = 1.38 × 10−7, and p = 0.026, respectively) and disease-free survival (DFS) (p = 0.00002, p = 1.21 × 10−7, and p = 0.036, respectively). Notably, the PCSK2 mutation demonstrated survival specificity uniquely in both the TCGA-KIRP (OS: p = 0.010 and DFS: p = 0.301) and Korean-KIRP (OS: p = 1.38 × 10−7 and DFS: p = 1.21 × 10−7) databases. Conclusions: We discovered and verified genes specific for the survival of PRCC patients in the TCGA-KIRP and Korean-KIRP databases. The survival gene signature, including PCSK2 commonly obtained from the 40 gene signature of TCGA and the 10 gene signature of the Korean database, is expected to provide insight into predicting the survival of PRCC patients and developing new treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Epstein–Barr virus (EBV)-associated gastric cancer is accepted as a distinct entity among gastric adenocarcinomas. It is particularly frequent in gastric remnant cancer (GCR), defined as cancer in the gastric stump several decades after distal gastric resection for benign disease. Gastric cancer in the West is a comparatively rare disease, and most of the published data stem from the East. Using population-based data from the West spanning the years from 2001 to 2016, we were able to show that a significantly higher proportion of GRCs compared to non-GRC proximally located cancers were EBV-positive, even in the West. The mode of presentation and findings at upper endoscopy were more subtle and differed significantly from proximally located non-GRC cancers, possibly making the GRCs more difficult to diagnose. Epstein–Barr virus (EBV) is associated with 5–10% of gastric cancers and is recognized as a distinct molecular subtype. EBV positivity is particularly high in gastric remnant cancer (GRC), which may inform the mode of clinical presentation and findings at endoscopy. Most data are from the East, and the question remains how this applies to a Western cohort. We conducted a population-based study in Central Norway, 2001–2016. Patients with GRC (n = 78) and patients with non-GRC proximally located cancer and available tissue for EBV status (n = 116, control group) were identified from the Norwegian Cancer Registry. Relevant data were collected from the individual patient journals. EBV status was assessed using in situ hybridization. The median latency time from the distal gastrectomy to GRC was 37.6 (range 15.7–68.0) years. GRC more often presented with GI bleeding, 31.0% vs. 16.1%, p = 0.017, and at endoscopy more seldom with an ulcer, 19.7% vs. 38.2%, p = 0.012, or a tumour, 40.8% vs. 66.4%, p < 0.001. For GRC, 18.7% were EBV-positive compared to 6.0% among the controls, p = 0.006. EBV status was not associated with patient age, sex, or Lauren histological type. No difference in long-term survival rates between GRC and controls was found or between EBV-positive vs. -negative GRCs. In conclusion, a higher proportion of GRC cases, compared to controls, are EBV positive, indicating different causative factors. The mode of clinical presentation and findings at endoscopy were more subtle in the patients with GRC. [ABSTRACT FROM AUTHOR]

Simple Summary: Little is known about the differences in liver cancer care between liver cancer referral centres, with and without an integrated liver transplant program. Even after adjusting for other important factors, such as tumour stage and patient characteristics, we found that liver transplant centres systematically used different local cancer treatments compared to non-transplant centres. Patients managed at liver transplant centres showed improved overall survival, which was evident even after considering the increased rates of transplantation. The management of early-stage hepatocellular carcinoma (HCC) is complex, with multiple treatment strategies available. There is a paucity of literature regarding variations in the patterns of care and outcomes between transplant and non-transplant centres. We conducted this real-world multi-centre cohort study in two liver cancer referral centres with an integrated liver transplant program and an additional eight non-transplant HCC referral centres across Australia to identify variation in patterns of care and key survival outcomes. Patients with stage Barcelona Clinic Liver Cancer (BCLC) 0/A HCC, first diagnosed between 1 January 2016 and 31 December 2020, who were managed at a participating site, were included in the study. Patients were excluded if they had a history of prior HCC or if they received upfront liver transplantation. A total of 887 patients were included in the study, with 433 patients managed at a liver cancer centre with a transplant program (LTC) and 454 patients managed at a non-transplant centre (NTC). Management at an LTC did not significantly predict allocation to resection (adjusted OR 0.75, 95% CI 0.50 to 1.11, p = 0.148). However, in those not receiving resection, LTC and NTC patients were systematically managed differently, with LTC patients five times less likely to receive upfront ablation than NTC patients (adjusted OR 0.19, 95% CI 0.13 to 0.28, p < 0.001), even after adjusting for tumour burden, as well as for age, gender, liver disease aetiology, liver disease severity, and medical comorbidities. LTCs exhibited significantly higher proportions of patients undergoing TACE for every tumour burden category, including those with a single tumour measuring 2 cm or less (p < 0.001). Using multivariable Cox proportional hazards analysis, management at a transplant centre was associated with reduced all-cause mortality (adjusted HR 0.71, 95% CI 0.51 to 0.98, p = 0.036), and competing-risk regression analysis, considering liver transplant as a competing event, demonstrated a similar reduction in risk (adjusted HR 0.70, 95% CI 0.50 to 0.99, p = 0.041), suggesting that the reduced risk of death is not fully explained by higher rates of transplantation. Our study highlights systematic differences in HCC care between large volume liver transplant centres and other sites, which has not previously been well-described. Further work is needed to better define the reasons for differences in treatment allocation and to aim to minimise unwarranted treatment variation to maximise patient outcomes across Australia. [ABSTRACT FROM AUTHOR]

Simple Summary: Microvesicles (MVs) are essential for inter-cellular signaling in health and disease. We analyzed MV levels in colorectal cancer patients and assessed their release in early-stage colorectal cancer and survival. Considering that all types of MV were elevated beginning in the very early stages of the disease, we believe that the study of circulating MV levels could provide evidence for their use in the early detection of colon cancer in patients. Background: The release of microvesicles (MVs) is an essential phenomenon for inter-cellular signaling in health and disease. The role of MVs in cancer is multidimensional and includes cancer cell survival, proliferation, and invasion. In this prospective study, we analyzed MV levels in colorectal cancer patients and assessed the importance of MV release in early-stage colorectal cancer and survival. Methods: This study included 98 patients and 15 controls. The characterization of MVs from human plasma was performed by flow cytometry using monoclonal antibodies. Results: The levels of total MVs and MUC-1-positive, tissue factor (TF)-positive, and endothelial cell-derived MVs (EMVs) were statistically significantly higher in the colon cancer patients than in the controls (p < 0.001). Furthermore, the subgroup of patients with very early-stage colorectal cancer also had statistically significant differences in the levels of the abovementioned MVs compared to the controls (p < 0.01). Highly differentiated tumors had lower levels of MUC-1-positive MVs (p < 0.02), EMVs (p < 0.002), and EMV/TF combinations (p < 0.001) versus those with tumors with low/intermediate differentiation. Conclusions: Our data demonstrate that the analysis of circulating MV levels in plasma could possibly become a tool for the early diagnosis of colon cancer at a very early stage of the disease. [ABSTRACT FROM AUTHOR]

Simple Summary: Colorectal cancer is a leading cause of death worldwide, with a significant number of patients presenting with liver metastases at diagnosis. The best treatment currently involves the surgical removal of these metastases, yet the optimal timing and method for this surgery are still debated among experts. Our analysis revealed no significant difference in overall survival and disease-free survival between a simultaneous surgery approach and a "bowel-first" approach, while a better 5-year overall survival (5-OS) was found when comparing the former to a "liver-first" approach. However, simultaneous surgeries are associated with a higher risk of perioperative mortality, suggesting that staged surgery might be more beneficial for high-risk patients. This emphasizes the need for personalized treatment plans. Our findings also suggest that anatomic and non-anatomic resections offer similar long-term survival benefits, highlighting the potential for more conservative surgeries to preserve liver function without compromising the effectiveness of cancer treatment. Surgical resection is the gold standard for treating synchronous colorectal liver metastases (CRLM). The resection of the primary tumor and metastatic lesions can follow different sequences: "simultaneous", "bowel-first", and "liver-first". Conservative approaches, such as parenchymal-sparing surgery and segmentectomy, may serve as alternatives to major hepatectomy. A comprehensive search of Medline, Epistemonikos, Scopus, and the Cochrane Library was conducted. Studies evaluating patients who underwent surgery for CRLM and reported survival results were included. Other secondary outcomes were analyzed, including disease-free survival, perioperative complications and mortality, and recurrence rates. Quality assessment was performed using the AMSTAR-2 method. No significant differences in overall survival, disease-free survival, and secondary outcomes were observed when comparing simultaneous to "bowel-first" resections, despite a higher rate of perioperative mortality in the former group. The 5-year OS was significantly higher for simultaneous resection compared to "liver-first" resection. No significant differences in OS and DFS were noted when comparing "liver-first" to "bowel-first" resection, or anatomic to non-anatomic resection. Our umbrella review validates simultaneous surgery as an effective oncological approach for treating SCRLM, though the increased risk of perioperative morbidity highlights the importance of selecting suitable patients. Non-anatomic resections might be favored to preserve liver function and enable future surgical interventions. [ABSTRACT FROM AUTHOR]

Simple Summary: This study suggests that GLR, along with other factors like CA 19-9 levels and symptoms, can help predict long-term survival outcomes in PDAC patients following surgical resection, aiding in the identification of high-risk individuals who may benefit from closer monitoring or more aggressive treatment approaches. Background: We retrospectively evaluated the usefulness of an elevated glucose-to-lymphocyte ratio (GLR) as a sensitive prognostic biomarker of disease-specific survival in 338 patients who underwent surgical resection of pancreatic ductal adenocarcinoma (PDAC). Methods: The optimal GLR cutoff value was determined using the method of Contal and O'Quigley. Patient demographics, clinical information, and imaging data were analyzed to identify preoperative predictors of long-term survival outcomes. Results: Elevated GLR correlated significantly with aggressive tumor biologic behaviors, such as a high carbohydrate antigen (CA) 19-9 level (p = 0.003) and large tumor size (p = 0.011). Multivariate analysis identified (1) GLR > 92.72 [hazard ratio (HR) = 2.475, p < 0.001], (2) CA 19-9 level > 145.35 (HR = 1.577, p = 0.068), and (3) symptoms (p = 0.064) as independent predictors of long-term, cancer-specific survival. These three risk factors were used to group patients into groups 1 (0 factors), 2 (1–2 factors), and 3 (3 factors), which corresponded to significantly different 5-year overall survival rates (50.2%, 34.6%, and 11.7%, respectively; p < 0.001). Conclusions: An elevated preoperative GLR is associated with aggressive tumor characteristics and is an independent predictor of poor postoperative prognosis in patients with PDAC. Further prospective studies are required to verify these findings. [ABSTRACT FROM AUTHOR]

Simple Summary: Despite the promising evidence of the Royal Marsden Hospital (RMH) score as a readily available prognostic biomarker in patients with cancer, the wide scale implementation in clinical practice as well as the true benefit in clinical decision-making is lacking. Therefore, we systematically reviewed the available evidence on the association between the RMH score and prognosis in patients with cancer. This comprehensive meta-analysis, encompassing over a hundred thousand patients, revealed a negative association between a higher RMH score and survival in cancer patients. The available evidence demonstrates that the RMH score is not only a selective biomarker for patients enrolled in clinical trials, but also a useful prognostic biomarker in a real-world setting. Future research should aim to validate and refine this score, ensuring its optimal application in clinical practice and decision-making. Background: Cancer remains a leading cause of death globally, necessitating the identification of prognostic biomarkers to guide treatment decisions. The Royal Marsden Hospital (RMH) score, based on readily available blood tests and clinical features, has emerged as a prognostic tool, although its performance across variable clinical scenarios is not thoroughly delineated. Therefore, we aimed to systematically assess the association between RMH score and survival in cancer patients. Methods: We conducted a systematic literature search across Pubmed, Scopus, and Web of Science databases for studies published up to 15 February 2024. We performed a meta-analysis with the generic inverse variance method with a random-effects model and reported hazard ratios (HR) with 95% confidence intervals (CI). Results: Nineteen studies encompassing 127,230 patients were included. A higher RMH score was significantly associated with worse overall survival (OS) (HR: 2.09, 95% CI: 1.87–2.33, p < 0.001) and progression-free survival (PFS) (HR: 1.80, 95% CI: 1.48–2.18, p < 0.001). This association was consistent across various subgroups, including study population (clinical trial vs. real-world cohort), geographic region, and tumor type. Conclusion: This meta-analysis, including over a hundred thousand patients, demonstrates a negative association between a higher RMH score and survival in cancer patients. The RMH score holds promise as a readily available prognostic tool across diverse cancer types and clinical settings. Future research should focus on validating and refining this score to aid clinical decision-making. [ABSTRACT FROM AUTHOR]

Simple Summary: Undifferentiated pleomorphic sarcomas (UPSs) represent 10–20% of all soft tissue sarcomas (STSs) and have quickly emerged as one of the more immune-sensitive types. There are few real-world data on the use of immune checkpoint blockade (ICB) in UPS patients and those with other high-grade pleomorphic STSs. This is a retrospective, observational study of all patients with metastatic high-grade pleomorphic sarcomas treated with FDA-approved ICB at MD Anderson Cancer Center intended to describe the efficacy and toxicity of ICB in this particular group of patients. We find that our outcomes are comparable to those in the published literature and pose a question regarding the need to further evaluate the optimal sequencing of radiotherapy and prior lines of systemic therapy. Background: Undifferentiated pleomorphic sarcomas (UPSs) are amongst the most common subtypes of soft-tissue sarcomas. Few real-world data on the use of immune checkpoint blockade (ICB) in UPS patients and other high-grade pleomorphic STS patients are available. Purpose: The purpose of our study is to describe the efficacy and toxicity of ICB in patients with advanced UPSs and other high-grade pleomorphic sarcomas treated at our institution. Methods: This is a retrospective, observational study of all patients with metastatic high-grade pleomorphic sarcomas treated with FDA-approved ICB at MD Anderson Cancer Center between 1 January 2015 and 1 January 2023. Patients included in trials for which results are not yet published were excluded. Results: Thirty-six patients with advanced/metastatic pleomorphic sarcomas were included. The median age was 52 years. A total of 26 patients (72%) had UPSs and 10 patients (28%) had other high-grade pleomorphic sarcomas. The median follow-up time was 8.8 months. The median PFS was 2.9 months. The 3-month PFS and 6-month PFS were 46% and 32%, respectively. The median OS was 12.9 months. The 12-month OS and 24-month OS were 53% and 29%, respectively. The best response, previous RT, and type of ICB treatment were significantly and independently associated with shorter PFS (p = 0.0012, p = 0.0019 and p = 0.036, respectively). No new safety signal was identified, and the toxicity was overall manageable with no toxic deaths and only four patients (11%) stopping treatment due to toxicity. Conclusions: Real-world retrospective data are consistent with the published literature, with a promising 6-month PFS of 32%. Partial or stable responders to ICB treatment have significantly improved PFS compared to progressors. [ABSTRACT FROM AUTHOR]

Simple Summary: The exact cellular origin of glioblastoma (GBM) remains uncertain, with prevalent theories suggesting emergence from transformed endogenous stem cells. These cells likely play pivotal roles in tumor initiation and progression. The impact of proximity of GBM to the brain's neurogenic zones on patient survival remains a lingering question. Our study investigated tumor infiltration into the subventricular zone (SVZ), the subgranular zone (SGZ) and the cortex alongside clinical variables, such as KPS score, multifocality and selected molecular markers. Utilizing a fully automated processing and segmentation pipeline, we objectively quantified these relationships in 177 IDH wild-type glioblastomas. Our findings support prior research indicating SVZ proximity as a predictor for poor survival, while SGZ proximity showed no significant impact. We also established new survival thresholds based on tumor mass fractions and minimal distances. Contrary to previous studies, we found no significant correlations between SVZ contact and multifocal growth pattern or MGMT promoter methylation. So far, the cellular origin of glioblastoma (GBM) needs to be determined, with prevalent theories suggesting emergence from transformed endogenous stem cells. Adult neurogenesis primarily occurs in two brain regions: the subventricular zone (SVZ) and the subgranular zone (SGZ) of the hippocampal dentate gyrus. Whether the proximity of GBM to these neurogenic niches affects patient outcome remains uncertain. Previous studies often rely on subjective assessments, limiting the reliability of those results. In this study, we assessed the impact of GBM's relationship with the cortex, SVZ and SGZ on clinical variables using fully automated segmentation methods. In 177 glioblastoma patients, we calculated optimal cutpoints of minimal distances to the SVZ and SGZ to distinguish poor from favorable survival. The impact of tumor contact with neurogenic zones on clinical parameters, such as overall survival, multifocality, MGMT promotor methylation, Ki-67 and KPS score was also examined by multivariable regression analysis, chi-square test and Mann–Whitney-U. The analysis confirmed shorter survival in tumors contacting the SVZ with an optimal cutpoint of 14 mm distance to the SVZ, separating poor from more favorable survival. In contrast, tumor contact with the SGZ did not negatively affect survival. We did not find significant correlations with multifocality or MGMT promotor methylation in tumors contacting the SVZ, as previous studies discussed. These findings suggest that the spatial relationship between GBM and neurogenic niches needs to be assessed differently. Objective measurements disprove prior assumptions, warranting further research on this topic. [ABSTRACT FROM AUTHOR]

Simple Summary: Little is known regarding the significance of tumor burden in the treatment of recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). Patients were stratified into high tumor burden (HTB) and low tumor burden (LTB) groups according to their tumor burden score. Our study showed tumor burden was significantly correlated with survival in R/M HNSCC patients, independent of PD-L1 status. HTB patients receiving EPF had better survival than those receiving PPF, regardless of PD-L1 expression. For LTB PD-L1 positive patients, there was a longer survival on PPF than EPF. For LTB PD-L1 negative patients, survival was similar between PPF and EPF. Hence, PD-L1 and TBS should be considered by the multi-disciplinary team for the treatment of R/M HNSCC. Background: The significance of tumor burden for survival is unknown for patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). The purpose of our study was to evaluate the prognostic impact of programmed death ligand-1 (PD-L1) and tumor burden score (TBS) in patients with R/M HNSCC. Patients and Methods: R/M HNSCC patients who were treated with cisplatin, 5-fluorouracil plus cetuximab (EPF) or pembrolizumab (PPF) as first-line treatment were included in our study. PD-L1 and TBS were estimated and correlated with treatment responses. Kaplan–Meier curves were plotted for outcomes estimation. Results: A total of 252 R/M HNSCC patients were included, with 126 high tumor burden (HTB) and 126 low tumor burden (LTB) patients. Median progression-free survival (PFS) was 7.1 months in LTB and 3.9 months in HTB (p < 0.001) and median overall survival (OS) was 14.2 months in LTB and 9.2 months in HTB (p = 0.001). Patients with LTB had better PFS and OS than those with HTB independent of PD-L1 status. Subgroup analysis showed HTB patients treated with EPF had better survival than those treated with PPF, regardless of PD-L1 expression. For LTB PD-L1 positive patients, there was a longer survival with PPF than EPF, while for LTB PD-L1 negative patients, survival was similar between PPF and EPF. Multivariate analysis exhibited that tumor burden was significantly correlated with OS. Conclusions: Tumor burden is significantly correlated with survival in patients with R/M HNSCC. PD-L1 and TBS should be taken into consideration to determine first-line treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Despite a lack of standardization and some open questions, a growing body of evidence supports the use of frailty to optimize the clinical management of patients with hematological malignancies. Several scores have been applied particularly to multiple myeloma, an entity that shares many characteristics with AL amyloidosis, both being frequently associated. To date, no study has focused on frailty in patients with AL amyloidosis. We aimed to define a practical evaluation of frailty and estimate its impact in survival in patients with systemic AL amyloidosis. Systemic AL amyloidosis is a challenging disease for which many patients are considered frail in daily clinical practice. However, no study has so far addressed frailty and its impact on the outcome of these patients. We built a simple score to predict mortality based on three frailty-associated variables: age, ECOG performance status (<2 vs. ≥2) and NT-proBNP (<8500 vs. ≥8500 ng/L). Four-hundred and sixteen consecutive newly diagnosed patients diagnosed at ten sites from the Spanish Myeloma Group were eligible for the study. The score was developed in a derivation cohort from a referral center, and it was externally validated in a multicenter cohort. Multivariate analysis showed that the three variables were independent predictors of survival. The score was able to discriminate four groups of patients in terms of overall survival and early mortality in both cohorts. Comorbidity was also analyzed with the Charlson comorbidity index, but it did not reach statistical significance in the model. A nomogram was created to easily estimate the mortality risk of each patient at each time point. This score is a simple, robust, and efficient approach to dynamically assess frailty-dependent mortality both at diagnosis and throughout follow-up. The optimal treatment for frail AL amyloidosis patients remains to be determined but we suggest that the estimation of frailty-associated risk could complement current staging systems, adding value in clinical decision-making in this complex scenario. [ABSTRACT FROM AUTHOR]

Simple Summary: Early detection and curative-intent surgery are crucial for improving survival rates in patients with early-stage non-small cell lung cancer (NSCLC). However, even after complete tumor resection in patients with pathological stage I NSCLC, recurrence rates and overall survival remain unfavorable. There is growing evidence suggesting that the location of the primary tumor, nodal upstaging, certain genetic mutations, and histological characteristics have been found to be more prevalent in tumors located in specific lung regions. To address this research gap, we conducted a multicenter retrospective study in Taiwan to explore the independent prognostic significance of tumor location in patients with completely resected pathological stage I NSCLC. The results suggest that patients with NSCLC located in the lower lobe, especially those that are histologically classified as IASLC Grade 3, may require additional attention and interventions to improve outcomes. These findings have implications for personalized treatment strategies and the identification of high-risk patients who may benefit from closer surveillance or adjuvant therapies. Previous studies suggested that the location of the primary tumor in non-small cell lung cancer (NSCLC) is associated with clinical features and prognosis, but results are conflicting. The purpose of this study was to explore tumor location as an independent risk factor of survival for patients with completely resected pathological stage I NSCLC. This was a multicenter retrospective study conducted in Taiwan. Included patients were diagnosed with stage I NSCLC and had undergone primary tumor resection. Variables including tumor location, pathological stage, histological differentiation, and International Association for the Study of Lung Cancer (IASLC) grade were evaluated for predictive ability for disease-free survival (DFS) and overall survival (OS). A total of 208 patients were included, with 123 (59.1%) patients having a primary tumor in the upper and middle lobes. The median duration of follow-up for survivors was 60.5 months. Compared to patients with IASLC Grade 3 disease, patients with Grade 1 disease had significantly longer DFS. Tumor location and IASLC grade were independent predictors for OS in multivariate analysis. Specifically, patients with NSCLC in the lower lobe and patients who are histologically classified as IASLC Grade 3 may have poorer prognosis and require greater attention to improve outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Accurately predicting survival in patients with cancer receiving palliative radiotherapy is important for clinical decision making in cancer care management and delivery. This remains a challenge due to the heterogeneity of cancer diagnoses and a wide variety of prognostic factors. This study aims to review the literature to identify prognostic factors for clinical use as well as prognostic tools available to clinicians treating this population of patients. Based on the literature, we formulated evidence-based recommendations for clinicians to implement into practice with the intention of improving prognostic accuracy and overall patient care. (1) Background: Prognostication in patients with cancer receiving palliative radiotherapy remains a challenge. To improve the process, we aim to identify prognostic factors in this population from the literature and offer evidence-based recommendations on prognostication in patients undergoing palliative radiotherapy for non-curable or advanced cancers. (2) Methods: A systematic review was performed on the medical literature from 2005 to 2023 to extract papers on the prognosis of palliative radiotherapy patients with advanced cancer. The initial selection was performed by at least two authors to determine study relevance to the target area. Studies were then classified based on type and evidence quality to determine final recommendations. (3) Results: The literature search returned 57 papers to be evaluated. Clinical and biological prognostic factors were identified from these papers to improve clinical decision making or construct prognostic models. Twenty prognostic models were identified for clinical use. There is moderate evidence supporting (i) evidence-based factors (patient, clinical, disease, and lab) in guiding decision making around palliative radiation; (ii) that certain biological factors are of importance; (iii) prognostication models in patients with advanced cancer; and that (iv) SBRT or re-irradiation use can be guided by predictions of survival by prognostic scores or clinicians. Patients with more favorable prognoses are generally better suited to SBRT or re-irradiation, and the use of prognostic models can aid in this decision making. (4) Conclusions: This evaluation has identified several factors or tools to aid in prognosis and clinical decision making. Future studies should aim to further validate these tools and factors in a clinical setting, including the leveraging of electronic medical records for data availability. To increase our understanding of how causal factors interact with palliative radiotherapy, future studies should also examine and include prediction of response to radiation as an outcome. [ABSTRACT FROM AUTHOR]

Simple Summary: Osteosarcoma is one of the most lethal bone tumors worldwide. Immune checkpoint blockades have achieved significant success in solid tumors; however, their role in osteosarcoma remains obscure. Therefore, we aim to explore the clinical significance of soluble immune checkpoint-related proteins in osteosarcoma in this study. We identified four soluble immune checkpoint-related proteins as predictors of progress-free survival and lung metastasis-free survival of osteosarcoma patients. Our findings indicated that soluble immune checkpoint-related proteins could be promising biomarkers for the outcomes and immunotherapy of osteosarcoma. Background: The immune checkpoint blockade remains obscure in osteosarcoma (OS). We aim to explore the clinical significance of soluble immune checkpoint (ICK)-related proteins in OS. Methods: We profiled 14 soluble ICK-related proteins (BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD-L1, PD-L2, TIM-3, CD28, CD80, CD137, CD27, and CTLA-4) in the plasma of 76 OS patients and matched controls. We evaluated the associations between the biomarkers and the risk of OS using unconditional multivariate logistic regression. The multivariate Cox model was utilized to develop the prediction model of OS. Immune subtypes were established from the identified biomarkers. Transcriptional data from GEO were analyzed to elucidate potential mechanisms. Results: We found that sTIM3, sCD137, sIDO, and sCTLA4 were significantly correlated with OS risk (all p < 0.05). sBTLA, sPDL2, and sCD27 were significantly associated with the risk of lung metastasis, whereas sBTLA and sTIM3 were associated with the risk of disease progression. We also established an immune subtype based on sBTLA, sPD1, sTIM3, and sPDL2. Patients in the sICK-type2 subtype had significantly decreased progression-free survival (PFS) and lung metastasis-free survival (LMFS) than those in the sICK-type1 subtype (log-rank p = 2.8 × 10−2, 1.7 × 10−2, respectively). Interestingly, we found that the trend of LMFS and PFS in the subtypes of corresponding ICK genes' expression was opposite to the results in the blood (log-rank p = 2.6 × 10−4, 9.5 × 10−4, respectively). Conclusion: Four soluble ICK-related proteins were associated with the survival of OS patients. Soluble ICK-related proteins could be promising biomarkers for the outcomes and immunotherapy of OS patients, though more research is warranted. [ABSTRACT FROM AUTHOR]

Simple Summary: Immunotherapy with PD-1/PD-L1 inhibitors has been shown to significantly improve the survival rates of non-small-cell lung cancer (NSCLC) patients in advanced or metastasised stages. In the present real-world data study, we examined patients with advanced or metastasised NSCLC and compared overall survival between a control group receiving a PD-1/PD-L1 inhibitor therapy and the combinatorial group receiving PD-1/PD-L1 inhibitors plus add-on Viscum album L. Our findings revealed that patients in the combinatorial group lived seven months longer in comparison to the control group (p < 0.001). Furthermore, in patients with a PD-L1-positive tumour that received first-line anti-PD-1/PD-L1 therapy, the adjusted hazard of death was reduced by 56% through the addition of Viscum album L. (p < 0.001). Our findings imply that the addition of Viscum album L. to PD-1/PD-L1 inhibitors is associated with improved survival in patients with advanced or metastasised NSCLC. A limitation of this study is the observational and non-randomised study design; prospective randomised trials are warranted. Immunotherapy with PD-1/PD-L1 inhibitors has significantly improved the survival rates of patients with metastatic non-small-cell lung cancer (NSCLC). Results of a real-world data study investigating add-on VA (Viscum album L.) to chemotherapy have shown an association with the improved overall survival of patients with NSCLC. We sought to investigate whether the addition of VA to PD-1/PD-L1 inhibitors in patients with advanced or metastasised NSCLC would have an additional survival benefit. In the present real-world data study, we enrolled patients from the accredited national registry, Network Oncology, with advanced or metastasised NSCLC. The reporting of data was performed in accordance with the ESMO-GROW criteria for the optimal reporting of oncological real-world evidence (RWE) studies. Overall survival was compared between patients receiving PD-1/PD-L1 inhibitor therapy (control, CTRL group) versus the combination of anti-PD-1/PD-L1 therapy and VA (combination, COMB group). An adjusted multivariate Cox proportional hazard analysis was performed to investigate variables associated with survival. From 31 July 2015 to 9 May 2023, 415 patients with a median age of 68 years and a male/female ratio of 1.2 were treated with anti-PD-1/PD-L1 therapy with or without add-on VA. Survival analyses included 222 (53.5%) patients within the CRTL group and 193 (46.5%) in the COMB group. Patients in the COMB group revealed a median survival of 13.8 months and patients in the CRTL group a median survival of 6.8 months (adjusted hazard ratio, aHR: 0.60, 95% CI: 0.43–0.85, p = 0.004) after adjustment for age, gender, tumour stage, BMI, ECOG status, oncological treatment, and PD-L1 tumour proportion score. A reduction in the adjusted hazard of death by 56% was seen with the addition of VA (aHR 0.44, 95% CI: 0.26–0.74, p = 0.002) in patients with PD-L1-positive tumours (tumour proportion score > 1%) treated with first-line anti-PD-1/PD-L1 therapy. Our findings suggest that add-on VA correlates with improved survival in patients with advanced or metastasised NSCLC who were treated with PD-1/PD-L1 inhibitors irrespective of age, gender, tumour stage, or oncological treatment. The underlying mechanisms may include the synergistic modulation of the immune response. A limitation of this study is the observational non-randomised study design, which only allows limited conclusions to be drawn and prospective randomised trials are warranted. [ABSTRACT FROM AUTHOR]

Simple Summary: Our study aimed to compare the operative and survival outcomes between radical antegrade modular pancreatosplenectomy (RAMPS) and conventional distal pancreatosplenctomy (cDPS), and identify prognostic factors for left-sided pancreatic cancer. We performed a retrospective propensity score match (PSM) analysis from 333 patients who underwent RAMPS or cDPS for left-sided pancreatic cancer. After PSM, 99 cohorts were matched in each group. We compared survival and operative outcomes and assessed prognostic factors. R0 resection rate was similar between both groups, and R1 resection rate was a significant prognostic factor. RAMPS was found to be safe, feasible, and to improve the number of retrieved lymph nodes. However, when R0 resection was similar in both groups, RAMPS was not associated with improved survival. Adjuvant treatment was a significant independent prognostic factor for overall and disease-free survival, but operation type was not. (1) Background: The aim of this study was to compare the survival benefit of radical antegrade modular pancreatosplenectomy (RAMPS) with conventional distal pancreatosplenectomy (cDPS) in left-sided pancreatic cancer. (2) Methods: A retrospective propensity score matching (PSM) analysis was conducted on 333 patients who underwent RAMPS or cDPS for left-sided pancreatic cancer at four tertiary cancer centers. The study assessed prognostic factors and compared survival and operative outcomes. (3) Results: After PSM, 99 patients were matched in each group. RAMPS resulted in a higher retrieved lymph node count than cDPS (15.0 vs. 10.0, p < 0.001). No significant differences were observed between the two groups in terms of R0 resection rate, blood loss, hospital stay, or morbidity. The 5-year overall survival rate was similar in both groups (cDPS vs. RAMPS, 44.4% vs. 45.2%, p = 0.853), and disease-free survival was also comparable. Multivariate analysis revealed that ASA score, preoperative CA19-9, histologic differentiation, R1 resection, adjuvant treatment, and lymphovascular invasion were significant prognostic factors for overall survival. Preoperative CA19-9, histologic differentiation, T-stage, adjuvant treatment, and lymphovascular invasion were independent significant prognostic factors for disease-free survival. (4) Conclusions: Although RAMPS resulted in a higher retrieved lymph node count, survival outcomes were not different between the two groups. RAMPS was a surgical option to achieve R0 resection rather than a standard procedure. [ABSTRACT FROM AUTHOR]

Simple Summary: Non-small cell lung cancer (NSCLC) is a common diagnosis from which many patients die. Blood tests reflecting systemic inflammation are routinely collected in the NSCLC clinic and may provide information on a patient's likelihood of a future event. Despite this, these "prognostic biomarkers" are not routinely used in clinical practice. In this narrative review we describe the key biomarkers of systemic inflammation and their prognostic significance in NSCLC. We highlight several challenges that limit their clinical application, including the need to; define an optimal inflammatory biomarker, consider NSCLC as a collection of different diseases, and explore outcomes with respect to how they may change clinical practice. We discuss how these challenges may be overcome through collaboration and the standardisation of recording and reporting of inflammatory biomarker studies. Further, we highlight the potential of modern electronic patient records and advanced data-analyses techniques in this area of research. Non-small cell lung cancer (NSCLC) is a common malignancy and is associated with poor survival outcomes. Biomarkers of systemic inflammation derived from blood tests collected as part of routine clinical care offer prognostic information for patients with NSCLC that may assist clinical decision making. They are an attractive tool, as they are inexpensive, easily measured, and reproducible in a variety of healthcare settings. Despite the wealth of evidence available to support them, these inflammatory biomarkers are not yet routinely used in clinical practice. In this narrative review, the key inflammatory indices reported in the literature and their prognostic significance in NSCLC are described. Key challenges limiting their clinical application are highlighted, including the need to define the optimal biomarker of systemic inflammation, a lack of understanding of the systemic inflammatory landscape of NSCLC as a heterogenous disease, and the lack of clinical relevance in reported outcomes. These challenges may be overcome with standardised recording and reporting of inflammatory biomarkers, clinicopathological factors, and survival outcomes. This will require a collaborative approach, to which this field of research lends itself. This work may be aided by the rise of data-driven research, including the potential to utilise modern electronic patient records and advanced data-analysis techniques. [ABSTRACT FROM AUTHOR]

Simple Summary: AIDS remains a worldwide epidemic, and approximately 1.2 million people are living with HIV in the United States. Burkitt lymphoma accounts for 10–35% of AIDS-defining lymphoma in people with HIV. The aim of our retrospective database study was to assess the long-term survival rates of HIV-associated Burkitt lymphoma on a national level. We found that there was an increased mortality rate of HIV-associated Burkitt lymphoma, and there was a 55% increased risk of death from months 3 to 60 from the time of diagnosis for HIV-associated Burkitt lymphoma compared to patients with Burkitt lymphoma without HIV. Additionally, risk of death was significantly decreased in patients with HIV treated with combination chemotherapy and immunotherapy compared to patients without HIV treated with combination chemotherapy and immunotherapy in the first 3 months following BL diagnosis. Background: Burkitt lymphoma (BL) accounts for 10–35% of AIDS-defining lymphoma in people with HIV (PWH). Previous research consisting of smaller cohorts has shown decreased survival for HIV-associated BL. This study aims to compare overall mortality in BL patients with and without HIV, while investigating impact of treatment modalities in HIV-associated BL. Methods: Using the 2004–2019 NCDB, we identified 4312 patients with stage 3 or 4 BL who had a known HIV status and received either chemotherapy alone or chemotherapy and immunotherapy. Time to death was evaluated using Kaplan–Meier survival estimates. Risk of death was evaluated using an extended multivariable Cox model adjusted for multiple factors and with a Heaviside function for HIV status by time period (0–3 month vs. 3–60 month). Results: Of the 4312 patients included, 1514 (35%) had HIV. For months 0–3 from time of diagnosis, HIV status was not associated with a statistically significant increase in risk of death (HR = 1.04, 95% CI: 0.86, 1.26, p = 0.6648). From month 3to 60, positive HIV status was associated with a 55% increase in risk of death compared to those without HIV (95% CI: 1.38, 1.75, p < 0.0001). Further, this difference in hazard rates (0–3 vs. 3–60) was statistically significant (HR = 1.49, 95% CI: 1.22–1.82, p < 0.001). Conclusions: There is an increased mortality rate from months 3 to 60 in BL patients with HIV compared to patients without HIV. Additionally, risk of death in the first 3 months is significantly decreased by 45% in patients with HIV treated with combination chemotherapy and immunotherapy compared to patients without HIV receiving combination chemotherapy and immunotherapy, providing valuable clinical insight into treatment decision making in the care of HIV-associated BL. [ABSTRACT FROM AUTHOR]

Simple Summary: Surgery with adequate lymphadenectomy (D2) currently represents the standard of care for resectable gastric cancer under most guidelines. However, super-extended lymphadenectomy (D2plus) may offer better locoregional control in advanced stages with a high risk of metastases to third-level nodes. In recent years, preoperative chemotherapy has become a novel issue in patients with locally advanced gastric cancer. To date, only a few studies have evaluated D2plus lymphadenectomy in patients with locally advanced or oligometastatic gastric cancer after preoperative therapy. The present study included a large series when compared with the current literature and reports limited morbidity/mortality rates and relevant survival outcomes. Super-extended (D2plus) lymphadenectomy after chemotherapy has been reported in only a few studies. This retrospective study evaluates survival outcomes in a Western cohort of locally advanced or oligometastatic gastric cancer patients who underwent D2plus lymphadenectomy after neoadjuvant chemotherapy. A total of 97 patients treated between 2010 and 2022 were included. Of these, 62 had clinical stage II/III disease, and 35 had stage IV disease. Most patients (65%) received preoperative DOC/FLOT chemotherapy. The mean number of lymph nodes harvested was 39. Pathological positive nodes in the posterior/para-aortic stations occurred in 17 (17.5%) patients. Lymphovascular invasion, ypN stage, clinical stage, and perineural invasion were predictive factors for positive posterior/para-aortic nodes. Postoperative complications occurred in 21 patients, whereas severe complications (grade III or more) occurred in 9 cases (9.3%). Mortality rate was 1%. Median overall survival (OS) was 59 months (95% CI: 13–106), with a five-year survival rate of 49 ± 6%; the five-year OS after R0 surgery was 60 ± 7%. In patients with positive posterior/para-aortic nodes, the median OS was 15 months (95% CI: 13–18). D2plus lymphadenectomy after chemotherapy for locally advanced or oligometastatic gastric cancer is feasible and associated with low morbidity/mortality rates. The incidence of pathological metastases in posterior/para-aortic nodes is not negligible even after systemic chemotherapy, with poor long-term survival. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigated the efficacy of combining radiofrequency ablation (RFA) with stenting versus stenting alone in treating inoperable cholangiocarcinoma. Through a systematic review and meta-analysis of randomized controlled trials, it assessed the impact of the treatment on overall survival and stent patency. Although the results show no significant difference in overall survival between the groups, there was a trend toward improved survival in the subgroup treated with RFA plus plastic stents. Stent patency was significantly better in the RFA group. Adverse events were not different between the groups. These findings suggest that RFA may offer benefits in palliative care for these patients, warranting further research to explore the potential cumulative effects of RFA. Endoluminal biliary radiofrequency ablation (RFA) has been proposed as a palliative treatment for patients with malignant biliary obstruction (MBO) in order to improve stent patency and survival. However, the existing data on patients with inoperable extrahepatic cholangiocarcinoma (eCCA) are conflicting. We performed a meta-analysis of randomized trials comparing RFA plus stenting versus stenting alone in patients with inoperable eCCA. We searched for trials published in the PubMed/MEDLINE, Scopus, and Cochrane databases up to November 2023. Data extraction was conducted from published studies, and a quality assessment was carried out in accordance with the guidelines recommended by the Cochrane Collaboration. Hazard ratios (HRs) with 95% CI were estimated from the trials. The primary endpoints of interest were overall survival and stent patency. Out of 275 results, 5 randomized trials and 370 patients were included. While overall survival was not different between the groups (HR 0.62; 95% CI 0.36–1.07; p = 0.09; I2 = 80%;), the subgroup analysis of studies employing plastic stents showed a trend toward better survival in the RFA-treated group (HR 0.42; 95% CI 0.22–0.80; p = 0.009; I2 = 72%). Stent patency was improved in patients receiving RFA (HR 0.64; 95% CI 0.45–0.90; p = 0.01; I2 = 23%). Adverse events were not different between the groups (OR 1.21; 95% CI 0.69–2.12; p = 0.50; I2 = 0%). Despite the promising results, high heterogeneity and potential biases in the included studies suggest the need for further high-quality randomized trials to explore the potential cumulative effects of RFA on CCA treatment outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Azacitidine (AZA) is an essential drug in the treatment of myelodysplastic syndromes (MDS) that has made it possible to extend patients' survival and improve their quality of life. Unfortunately, despite the widespread use of AZA, its prognostic factors for response still remain unknown. Here, we retrospectively analyzed the efficacy and safety of AZA therapy in 79 patients with MDS in a real-life setting. Furthermore, we provided some potential biomarkers of response and survival. The study confirmed that the achievement of response to AZA is not mandatory for obtaining a survival benefit in patients with MDS. Unfavorable cytogenetic risk was determined to be the most negative prognostic factor for both response and survival. Moreover, older age, a complex or monosomal karyotype, higher IPSS or IPSS-R risk and a higher level of serum ferritin level were associated with significantly shorter survival. Azacitidine (AZA) is recognized as a vital drug used in the therapy of myelodysplastic syndromes (MDS) due to its beneficial effect on survival and quality of life. Nevertheless, many patients fail to respond to AZA treatment, as prognostic factors still are not identified. The present retrospective analysis included 79 patients with MDS treated with AZA as first-line therapy in a real-life setting. The percentage of patients with good, intermediate, and poor cytogenetics was 46.8%, 11.4%, and 34.2%, respectively. The overall response rate (complete remission [CR], partial remission [PR], and hematological improvement [HI]) was 24%. The CR, PR, and HI rates were 13.9%, 2.5%, and 7.6%, respectively. Stable disease (SD) was documented in 40.5% of patients. The median overall survival (OS) and progression-free survival (PFS) were 17.6 and 14.96 months, respectively. Patients with ORR and SD had a significantly longer median OS (23.8 vs. 5.7 months, p = 0.0005) and PFS (19.8 vs. 3.5 months, p < 0.001) compared to patients who did not respond to AZA. In univariate analysis, only an unfavorable cytogenetic group was a prognostic factor of a lower response rate (p = 0.03). In a multivariate model, older age (p = 0.047), higher IPSS (International Prognostic Scoring System) risk (p = 0.014), and higher IPSS-R cytogenetic risk (p = 0.004) were independent factors of shorter OS. Independent prognostic factors for shorter PFS were age (p = 0.001), IPSS risk (p = 0.02), IPSS cytogenetic risk (p = 0.002), and serum ferritin level (p = 0.008). The safety profile of AZA was predictable and consistent with previous studies. In conclusion, our study confirms the efficacy and safety of AZA in a real-world population and identifies potential biomarkers for response and survival. [ABSTRACT FROM AUTHOR]

Simple Summary: An important component in the study of survival in breast cancer patients is how the tumor is detected. This involves examining whether and to what extent survival differs when the tumor is detected, for example, by screening or by symptoms. In such an analysis, it is important to note that survival times are influenced by several biases. One important factor is the bias due to the so-called lead time, i.e., the time by which the diagnosis has been brought forward by screening. Therefore, survival may appear to be longer even if earlier diagnosis did not affect disease progression. We examine whether there is a remaining survival difference after correction for bias that could be attributable to the mode of detection, for example, because of higher quality of care. These results can then be used to further improve the survival of breast cancer patients. (1) Background: Screen-detected breast cancer patients tend to have better survival than patients diagnosed with symptomatic cancer. The main driver of improved survival in screen-detected cancer is detection at earlier stage. An important bias is introduced by lead time, i.e., the time span by which the diagnosis has been advanced by screening. We examine whether there is a remaining survival difference that could be attributable to mode of detection, for example, because of higher quality of care. (2) Methods: Women with a breast cancer (BC) diagnosis in 2000–2022 were included from a population-based cancer registry from Schleswig-Holstein, Germany, which also registers the mode of cancer detection. Mammography screening was available from 2005 onwards. We compared the survival for BC detected by screening with symptomatic BC detection using Kaplan–Meier, unadjusted Cox regressions, and Cox regressions adjusted for age, grading, and UICC stage. Correction for lead time bias was carried out by assuming an exponential distribution of the period during which the tumor is asymptomatic but screen-detectable (sojourn time). We used a common estimate and two recently published estimates of sojourn times. (3) Results: The analysis included 32,169 women. Survival for symptomatic BC was lower than for screen-detected BC (hazard ratio (HR): 0.23, 95% confidence interval (CI): 0.21–0.25). Adjustment for prognostic factors and lead time bias with the commonly used sojourn time resulted in an HR of 0.84 (CI: 0.75–0.94). Using different sojourn times resulted in an HR of 0.73 to 0.90. (4) Conclusions: Survival for symptomatic BC was only one quarter of screen-detected tumors, which is obviously biased. After adjustment for lead-time bias and prognostic variables, including UICC stage, survival was 27% to 10% better for screen-detected BC, which might be attributed to BC screening. Although this result fits quite well with published results for other countries with BC screening, further sources for residual confounding (e.g., self-selection) cannot be ruled out. [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate cancer survival among US firefighters, who undergo regular medical check-ups and have unique exposures, has not been well-studied. Using population-based Florida cancer registry data, this retrospective study compared 1058 firefighter prostate cancer cases to patients with prostate cancer in the general population, finding significantly better five-year survival (96.1% vs. 94.2%) in firefighters. Firefighters were diagnosed earlier, had more localized cancers, and underwent surgery more often. However, older firefighters with regional or distant-stage cancer faced a higher risk of death. Enhanced survival in firefighters may be due to increased PSA testing, but further research is needed to understand factors influencing aggressive disease development and the impact of surgical treatments on their quality of life. Introduction: Survival outcomes for prostate cancer among specific occupational groups prone to regular medical check-ups vis-à-vis the general population have been understudied. For firefighters, a demographic subject to rigorous medical evaluations, possessing above-average medical expertise, and exposed to specific carcinogens of interest, prostate cancer survival in the US has never been studied. Methods: We conducted a retrospective study, utilizing data from the Florida Cancer Data System spanning 2004 to 2014, coupled with firefighter certification records from the Florida State Fire Marshal's Office. Our study cohort consisted of 1058 prostate cancer cases among firefighters as well as prostate cases for the Florida general population (n = 150,623). We compared cause-specific survival between the two using Cox regression models adjusted for demographics and clinical characteristics, including PSA levels, Gleason scores, and treatment modalities. Results: Firefighters demonstrated a higher five-year cause-specific survival rate (96.1%, 95% CI: 94.7–97.1%) than the general population (94.2%, 95%CI: 94.1–94.3%). Overall, firefighters' diagnoses were established at younger ages (median age 63 vs. 67 in the general population), exhibited a higher proportion of localized stage cancers (84.7% vs. 81.1%), and had a greater utilization of surgery (46.4% vs. 37.6%), a treatment modality with a high success rate but potential side effects. In multivariable analysis, firefighters displayed a survival advantage for localized stage (adjusted hazard ratio [aHR] = 0.53; 95%CI: 0.34–0.82). However, for regional or distant stages, firefighters aged 65 and above exhibited a higher risk of death (aHR = 1.84; 95% CI: 1.18–2.86) than the general population. Conclusion: Firefighters experience enhanced prostate cancer survival, primarily in cases diagnosed at localized stages, likely due to increased PSA testing. Nonetheless, for regional or distant stage, survival among older firefighters' lags behind that of the general population. Further investigations are warranted to unravel factors influencing the development of aggressive disease beyond PSA and Gleason scores in this population, as well as to assess the impact of a higher rate of surgical treatment on firefighters' quality of life. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aimed to pinpoint immune-related genes that show heightened activity in cancerous tissue and explore their correlation with cell infiltration in the tumor microenvironment using bioinformatics analysis. By examining gene expression from both stomach cancer and adjacent healthy tissues, we aimed to uncover their significance in cancer development and their impact on the body's immune response. We identified several genes, including FN1, COL1A2, THBS2, COL3A1, COL5A1, and BGN, which appear to be associated with poorer outcomes for stomach cancer patients. These genes also demonstrate connections to specific immune cells within cancerous tissue. Understanding the role of these genes in the immune response to cancer could facilitate the development of novel treatments and enhance prognostic capabilities for individuals with stomach cancer. Objective: Gastric carcinoma (GC) is the fifth most commonly diagnosed cancer and the third leading cause of cancer-related deaths globally. The tumor microenvironment plays a significant role in the pathogenesis, prognosis, and response to immunotherapy. However, the immune-related molecular mechanisms underlying GC remain elusive. Bioinformatics analysis of the gene expression of GC and paracancerous healthy tissues from the same patient was performed to identify the key genes and signaling pathways, as well as their correlation to the infiltration of the tumor microenvironment (TME) by various immune cells related to GC development. Methods: We employed GSE19826, a gene expression profile from the Gene Expression Omnibus (GEO), for our analysis. Functional enrichment analysis of Differentially Expressed Genes (DEGs) was conducted using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes database. Results: Cytoscape software facilitated the identification of nine hub DEGs, namely, FN1, COL1A1, COL1A2, THBS2, COL3A1, COL5A1, APOE, SPP1, and BGN. Various network analysis algorithms were applied to determine their high connectivity. Among these hub genes, FN1, COL1A2, THBS2, COL3A1, COL5A1, and BGN were found to be associated with a poor prognosis for GC patients. Subsequent analysis using the TIMER database revealed the infiltration status of the TME concerning the overexpression of these six genes. Specifically, the abovementioned genes demonstrated direct correlations with cancer-associated fibroblasts, M1 and M2 macrophages, myeloid-derived suppressor cells, and activated dendritic cells. Conclusion: Our findings suggest that the identified hub genes, particularly BGN, FN1, COL1A2, THBS2, COL3A1, and COL5A1, play crucial roles in GC prognosis and TME cell infiltration. This comprehensive analysis enhances our understanding of the molecular mechanisms underlying GC development and may contribute to the identification of potential therapeutic targets and prognostic markers for GC patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Metastasis, a critical aspect of oncologic diseases, is intricately governed by genetic factors. This article delves into the role of the ribosomal RNA processing 1 homolog B (RRP1B) gene in metastasis regulation, investigating its implications in human cervical cancer. We analyzed five RRP1B polymorphisms in 172 cervical cancer patients to understand their associations with disease characteristics and survival. Certain variations were linked to decreased tumor size, reduced metastasis risk, and improved overall survival, suggesting their potential as markers for predicting prognosis in cervical cancer. Metastasis is a key determinant of cancer progression, influenced significantly by genetic mechanisms. RRP1B, primarily a nucleolar protein, emerges as a suppressor of metastasis, forming alliances with various cellular components and modulating gene expression. This study investigates the involvement of the ribosomal RNA processing 1 homolog B (RRP1B) gene in metastasis regulation in cervical cancer. Through a comprehensive analysis of 172 cervical cancer patients, we evaluated five RRP1B single nucleotide polymorphisms (SNPs) (rs2838342, rs7276633, rs2051407, rs9306160, and rs762400) for their associations with clinicopathological features and survival outcomes. Significant associations were observed between specific genetic variants and clinicopathological parameters. Notably, the A allele of rs2838342 was associated with reduced odds of advanced tumor size, worse prognosis, and, preliminarily, distant metastasis, while the T allele of rs7276633 correlated with a decreased risk of higher tumor size and worse prognosis. Additionally, the C allele of rs2051407 demonstrated protective effects against larger tumors, metastasis, and adverse prognosis. The rs9306160 C allele exhibited a protective effect against metastasis. The rs762400 G allele was significant for reduced tumor size and metastasis risk. Furthermore, the rs2838342 A allele, rs7276633 T allele, rs2051407 C allele, and rs762400 G allele were associated with improved overall survival, demonstrating their potential significance in predicting prognoses in cervical cancer. Linkage disequilibrium and haplotypes analysis enabled us to evaluate the collective effect of the analyzed SNPs, which was in line with the results of allelic models. Our findings underscore the clinical relevance of RRP1B SNPs as prognostic markers in cervical cancer, shedding light on the intricate interplay between genetic factors and disease-progression dynamics. This research provides critical insights for future investigations and underscores the importance of incorporating RRP1B SNP detection into prognostic-assessment tools for accurate prediction of disease outcomes in cervical cancer. [ABSTRACT FROM AUTHOR]

MDM2-SNP309 (rs2279744), a common genetic modifier of cancer incidence in Li-Fraumeni syndrome, modifies risk, age of onset, or prognosis in a variety of cancers. Melanoma incidence and outcomes vary by sex, and although SNP309 exerts an effect on the estrogen receptor, no consensus exists on its effect on melanoma. MDM2 and MDM4 restrain p53-mediated tumor suppression, independently or together. We investigated SNP309, an a priori MDM4-rs4245739, and two coinherited variants, in a population-based cohort of 3663 primary incident melanomas. Per-allele and per-haplotype (MDM2_SNP309-SNP285; MDM4_rs4245739-rs1563828) odds ratios (OR) for multiple-melanoma were estimated with logistic regression models. Hazard ratios (HR) for melanoma death were estimated with Cox proportional hazards models. In analyses adjusted for covariates, females carrying MDM4-rs4245739*C were more likely to develop multiple melanomas (ORper-allele = 1.25, 95% CI 1.03-1.51, and Ptrend = 0.03), while MDM2-rs2279744*G was inversely associated with melanoma-death (HRper-allele = 0.63, 95% CI 0.42-0.95, and Ptrend = 0.03). We identified 16 coinherited expression quantitative loci that control the expression of MDM2, MDM4, and other genes in the skin, brain, and lungs. Our results suggest that MDM4/MDM2 variants are associated with the development of subsequent primaries and with the death of melanoma in a sex-dependent manner. Further investigations of the complex MDM2/MDM4 motif, and its contribution to the tumor microenvironment and observed associations, are warranted.

Post-transplant lymphoproliferative disorders (PTLD) are heterogenous lymphoproliferative disorders that develop as a consequence of immunosuppression in transplant recipients. We sought to determine if subtypes of PTLD correlated with different outcomes. We performed a retrospective review of PTLD occurring in pediatric heart transplant recipients. A total of 558 children and infants underwent cardiac transplantation at our institution between 1985 and 2019 and were followed until March 2021. Forty-nine of 558 patients developed PTLD (8.8%). As compared to older children (>one year of age), infant recipients (p = 0.04). Although not reaching statistical significance, patients with a shorter time to PTLD diagnosis showed a trend toward higher rates of M-PTLD or cHL. As expected, the overall survival (OS) of patients with M-PTLD or cHL was significantly lower than patients with non-destructive or polymorphic PTLD.