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Simple Summary: This paper characterizes the immunotherapy-related adverse effects in the oral tissues, in a large series of patients. This includes a description of the severity of oral symptoms, immediate clinical presentation, treatment, chronicity despite holding the immunotherapy, and the development of oral cancer. The management of these patients exemplified new diagnostic tools, detailed clinical presentation that may assist to differentiate between various oral irAEs and outlines unique adjustments in the topical treatment and inclusion of a new treatment modality for these irAEs. Lastly, this paper raises the awareness for second primary oral cancer and possible risk for oral malignant transformation. (1) Background: Immunotherapy-related adverse effects (irAEs) have been reported to manifest in oral tissues, mainly as lichenoid and non-lichenoid lesions and salivary gland dysfunction; however, the characterization of oral irAEs and their clinical impact is limited. (2) Methods: This is a retrospective clinical chart review of 14 patients with oral irAEs, describing the impact of the oral irAEs in terms of the immediate effect, treatment, chronicity of the irAEs and the development of oral cancer. (3) Results: Common symptoms were pain and dry mouth, causing no-to-severe pain and/or dry mouth sensation. The immediate sequala ranged from sensitivity to certain foods up to elimination of oral intake. Treatment included conventional palliation techniques with or without systemic steroids. Discontinuation of the immunotherapy agents was required in 6 patients. Innovative treatment modalities included photobiomodulation for oral mucosal pain relief, and salivary gland intraductal irrigations for relief of salivary gland hypofunction. Late sequala included the development of proliferative leukoplakia and oral cancer. (4) Conclusions: Patients treated with immunotherapy may develop debilitating oral irAEs. They should be followed for oral involvement so treatment may be initiated when the symptoms are mild to avoid discontinuation of the immunotherapy. Patients that develop oral lichenoid lesions should receive long-term follow-up, as they may have higher risk for oral cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with multiple myeloma (MM) who become refractory to three or more lines of therapy (RRMM patients) have few valid therapeutic alternatives. Among them, drugs directed against the BCMA antigen expressed in plasma cells are very appealing. Belantamab-mafodotin (belamaf) is the first antibody-drug conjugate against BCMA ready for clinical use. In this paper, we report the Spanish experience of belamaf monotherapy in 156 patients with RRMM. The overall response rate was 41.8%, with 39.8% of patients achieving a partial response or better. Median progression-free survival was 3.61 months, but interestingly, it increased to 14.47 months in patients achieving a minimal response or better. Treatment was well tolerated, ocular events being the most reported toxicity (87.9%; grade ≥ 3, 33.7%), but only two patients discontinued treatment due to side effects. Overall, our results confirm the safety and efficacy of belamaf in this poor prognosis subset of patients. Belantamab-mafodotin (belamaf) is a novel antibody-drug conjugate targeting B-cell maturation antigen that showed anti-myeloma activity in patients with relapsed and refractory multiple myeloma (RRMM). We performed an observational, retrospective, and multicenter study aimed to assess the efficacy and safety of single-agent belamaf in 156 Spanish patients with RRMM. The median number of prior therapy lines was 5 (range, 1–10), and 88% of patients were triple-class refractory. Median follow-up was 10.9 months (range, 1–28.6). The overall response rate was 41.8% (≥CR 13.5%, VGPR 9%, PR 17.3%, MR 2%). The median progression-free survival was 3.61 months (95% CI, 2.1–5.1) and 14.47 months (95% CI, 7.91–21.04) in patients achieving at least MR (p < 0.001). Median overall survival in the entire cohort and in patients with MR or better was 11.05 months (95% CI, 8.7–13.3) and 23.35 (NA-NA) months, respectively (p < 0.001). Corneal events (87.9%; grade ≥ 3, 33.7%) were the most commonly adverse events, while thrombocytopenia and infections occurred in 15.4% and 15% of patients, respectively. Two (1.3%) patients discontinued treatment permanently due to ocular toxicity. Belamaf showed a noticeably anti-myeloma activity in this real-life series of patients, particularly among those achieving MR or better. The safety profile was manageable and consistent with prior studies. [ABSTRACT FROM AUTHOR]

Simple Summary: In the modern era, characterized by parenchymal-sparing procedures, in some cases pneumonectomy remains the only therapeutic approach to achieving oncological radicality. One of the most feared complications is undoubtedly respiratory failure and ARDS. Its cause after pneumonectomy is still unclear, and the study of risk factors is a subject of debate. In this paper, we evaluate the main risk factors for ARDS of a large cohort of patients and we classify them in four classes of growing risk in order to quantify their postoperative risk of ARDS and facilitate their global management. (1) Background: The cause of ARDS after pneumonectomy is still unclear, and the study of risk factors is a subject of debate. (2) Methods: We reviewed a large panel of pre-, peri- and postoperative data of 211 patients who underwent pneumonectomy during the period 2014–2021. Univariable and multivariable logistic regression was used to quantify the association between preoperative parameters and the risk of developing ARDS, in addition to odds ratios and their respective 95% confidence intervals. A backward stepwise selection approach was used to limit the number of variables in the final multivariable model to significant independent predictors of ARDS. A nomogram was constructed based on the results of the final multivariable model, making it possible to estimate the probability of developing ARDS. Statistical significance was defined by a two-tailed p-value < 0.05. (3) Results: Out of 211 patients (13.3%), 28 developed ARDS. In the univariate analysis, increasing age, Charlson Comorbidity Index and ASA scores, DLCO < 75% predicted, preoperative C-reactive protein (CRP), lung perfusion and duration of surgery were associated with ARDS; a significant increase in ARDS was also observed with decreasing VO2max level. Multivariable analysis confirmed the role of ASA score, DLCO < 75% predicted, preoperative C-reactive protein and lung perfusion. Using the nomogram, we classified patients into four classes with rates of ARDS ranking from 2.0% to 34.0%. (4) Conclusions: Classification in four classes of growing risk allows a correct preoperative stratification of these patients in order to quantify the postoperative risk of ARDS and facilitate their global management. [ABSTRACT FROM AUTHOR]

Simple Summary: There is a growing need to clarify the effect of modifiable lifestyle factors such as obesity on outcomes of multiple myeloma (MM). In this paper, we examined the associations between body mass index (BMI) at different periods of life up to the time of diagnosis and overall survival among patients newly diagnosed with multiple myeloma. The key findings are that BMIs before and at the time of diagnosis were not associated with overall survival in MM, except that a higher BMI at diagnosis was associated with a better overall survival for females, irrespective of race/ethnicity. This is the first evidence that the BMI-survival association may differ by sex. Obesity is associated with survival in several solid tumors and non-Hodgkin lymphoma, but its impact on multiple myeloma (MM) survival is unclear. We examined the associations between body mass index (BMI) at different periods of life up to the time of diagnosis and overall survival (OS) among 563 patients newly diagnosed with MM in 2010–2019. BMI at diagnosis was calculated using measured height and weight from electronic medical records (EMR). BMIs at age 20, maximum during adulthood, and 5 years before diagnosis were calculated using self-reported weights and measured height from EMR. Over a median follow-up of 49.3 months, 191 (33.93%) deaths were identified. We used multivariable Cox proportional-hazards models to examine the associations between BMIs and OS. Height as well as BMI before and at diagnosis was not associated with OS, but there is a U-shape association between weight and OS. Higher BMIs at diagnosis were associated with better OS among females (HR = 0.39 [0.22–0.71]), irrespective of race. In conclusion, our results suggest that BMI at different periods of life up to the time of diagnosis may not be associated with OS in MM, except that a higher BMI at diagnosis was associated with superior OS for females. [ABSTRACT FROM AUTHOR]

Simple Summary: The early detection of lung nodules is important for patient treatment and follow-up. Many researchers are investigating deep-learning-based lung nodule detection to ease the burden of lung nodule detection by radiologists. The purpose of this paper is to provide guidelines for collecting lung nodule data to facilitate research. We collected chest computed tomography scans reviewed by radiologists at three hospitals. In addition, several experiments were conducted using the large-scale open dataset, LUNA16. As a result of the experiment, it was possible to prove the value of using the collected data compared to using LUNA16. We also demonstrated the effectiveness of transfer learning from pre-trained learning weights in LUNA16. Finally, our study provides information on the amount of lung nodule data that must be collected to stabilize lung nodule detection performance. Early detection of lung nodules is essential for preventing lung cancer. However, the number of radiologists who can diagnose lung nodules is limited, and considerable effort and time are required. To address this problem, researchers are investigating the automation of deep-learning-based lung nodule detection. However, deep learning requires large amounts of data, which can be difficult to collect. Therefore, data collection should be optimized to facilitate experiments at the beginning of lung nodule detection studies. We collected chest computed tomography scans from 515 patients with lung nodules from three hospitals and high-quality lung nodule annotations reviewed by radiologists. We conducted several experiments using the collected datasets and publicly available data from LUNA16. The object detection model, YOLOX was used in the lung nodule detection experiment. Similar or better performance was obtained when training the model with the collected data rather than LUNA16 with large amounts of data. We also show that weight transfer learning from pre-trained open data is very useful when it is difficult to collect large amounts of data. Good performance can otherwise be expected when reaching more than 100 patients. This study offers valuable insights for guiding data collection in lung nodules studies in the future. [ABSTRACT FROM AUTHOR]

Simple Summary: High local failure and treatment-related morbidity represent a great challenge for postcricoid carcinoma which appears to be more aggressive and requires more morbid oncologic surgery with reconstruction of the larynx and hypopharynx. This paper presents a retrospective analysis focusing on the evaluation of clinical characteristics, therapeutic approaches, quality of swallowing, voice rehabilitation, and verbal communication after a long-term follow-up. To date, this is the first and largest cohort published to reveal a deep understanding of clinical routines in postcricoid carcinoma. Background: Postcricoid carcinoma is a rare but aggressive type of hypopharyngeal carcinoma with poor prognosis and high mortality; thus, it is indispensable to investigate the surgical efficacy and multimodal strategies. Methods: This retrospective study included postcricoid carcinoma patients undergoing surgical resection from 2008 to 2022. Treatment methods and clinical characteristics were analyzed to evaluate prognostic factors for oncological outcomes. Results: Of 72 patients, 13 cases were in the I–II stage and 59 in the III–IV stage. The overall survival (OS) was 50.0%; the laryngeal function preservation rate was 69.4%. Univariate analysis found that high mortality was associated with low tumor differentiation, lymph node metastasis, neck recurrence, and smoke history via log-rank test (p < 0.05); postoperative radiotherapy (RT) remained positive in OS (p = 0.04). The multivariable model further revealed that lymph node metastasis was a dominant determinant after accounting for covariates (HR 1.75; 95% CI 0.85–3.59). The data also indicated that neoadjuvant chemotherapy (NAC) and tumor diameter ≤ 2 cm were causing lower rates of pharyngeal fistula and locoregional relapse. Conclusions: Surgeons should emphasize high-risk features and optimize individualized surgical procedures for postcricoid carcinoma patients. Combined with multimodal treatments, it is feasible to reconstruct laryngeal function and lessen postoperative morbidities in advanced patients. [ABSTRACT FROM AUTHOR]

Simple Summary: When it comes to advanced vulval cancer management, there is a critical quandary to consider. This is owing to the severe negative impact of demolitive surgery on women who are afflicted by both functional and psychological consequences of the procedure. Primary closure of vulvar and/or perineal defects can be accomplished without difficulty in many situations, but this is accompanied by tension of the skin closure and distortion of the anatomy. In these circumstances, reconstructive surgery will be required to restore the anatomical and functional characteristics of the vulva. In this paper, we share our substantial expertise of primary closure versus reconstruction after demolitive surgery of advanced vulvar cancer, and we discuss our findings in light of the literature. (1) Background: plastic reconstruction in vulvar surgery can lead to a better treatment outcome than primary closure. This study aims to compare the preoperative parameters (co-morbidities and tumor size) and postoperative results (tumor free margins and wound healing) between the primary closure and reconstructive surgery after vulvar cancer surgery; (2) Methods: this is a retrospective analysis of prospectively collected data from 2009 to 2021 at a tertiary cancer institution; (3) Results: 177 patients were included in the final analysis (51 patients had primary closure PC and 126 had reconstructive surgery RS). About half (49%) of the PC patients had no co-morbidities (p = 0.043). The RS group had a 45 mm median maximal tumor diameter compared to the PC group's 23 mm (p = 0.013). More than 90% of RS and 80% of PC had tumor-free margins (p = 0.1). Both groups had anterior vulvar excision as the most common surgery (52.4% RS vs. 23.5% PC; p = 0.001). Both groups had identical rates of wound healing disorders. In a median follow-up of 39 months; recurrent disease was found in 23.5% of PC vs. 10.3% in RS (p = 0.012). In terms of overall survival there was no significant difference between the both groups; (4) Conclusions: reconstructive vulvar surgery enables enhanced complete resection rates of larger vulvar tumors with better anatomical restoration and a comparable wound recovery in comparison to primary closure. This results in a lower recurrence rate despite the increased tumor volume. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer (BCa) is a pathology that affects the world population. Patients present risk factors for osteopenia and osteoporosis, such as chronic stress, estrogen deprivation due to hormonal treatment, a menopausal status, and decreased physical activity. An available alternative is the use of nonselective beta blockers (nsBBs) that have antitumoral properties, and in other diseases, antiresorptive and osteoforming effects. We demonstrated that BCa patients taking nsBBs had a greater bone mineral density and a lower incidence of osteoporosis and osteopenia than untreated patients. Although our study has several limitations, such as its retrospective design and single-center population, it revealed promising effects of nsBBs on the prevention and treatment of osteoporosis and osteopenia in patients with BCa. Breast cancer (BCa) is related to chronic stress and can reduce the bone mineral density (BMD) through neurochemicals related to beta-adrenergic receptor (ADRB) 1 and 2. Selective beta blockers (sBBs) and nonselective beta blockers (nsBBs) are used to treat systemic arterial hypertension (SAH) and may have osteoprotective effects, as they inhibit ADRBs. To evaluate the effects of sBBs and nsBBs on the BMD of Mexican patients with BCa. A retrospective study was conducted. We included 191 Mexican women with BCa without SAH and with SAH treated with nsBBs, sBBs, and diuretics. BMD was evaluated using a bone density scan (DEX scan). A greater average BMD (p < 0.05) was observed in patients with prior treatment with both nsBBs and sBBs (0.54 ± 0.94 and −0.44 ± 1.22, respectively) compared to patients treated with diuretics or without SAH (−1.73 ± 0.83 and −1.22 ± 0.98, respectively). Regarding the diagnosis of osteoporosis/osteopenia, no cases were observed in patients treated with nsBBs, whereas 5.6% of the patients treated with sBBs presented osteopenia. A total of 23.1% and 10.6% patients managed with diuretics or without treatment presented with osteoporosis and 61.5% and 48% patients managed with loop diuretics and without treatment presented with osteopenia, respectively (p < 0.05). Treatment with nsBBs is a promising option for the prevention and management of osteoporosis/osteopenia in Mexican patients with BCa; however, further prospective studies are needed. [ABSTRACT FROM AUTHOR]

Simple Summary: As more cancer patients with advanced disease present to the emergency department (ED), data on outcomes of cardiopulmonary resuscitation (CPR) are needed to help counsel patients before and during an acute event. We investigated the characteristics of cancer patients who required CPR, their outcomes, and how prior advanced care planning (ACP) influenced these outcomes. Few studies have specifically looked at these data in an emergency department, where medical history is limited and the need for acute intervention often precludes discussion of therapeutic limitations. We found cardiopulmonary resuscitation of cancer patients to be rare in the ED. Although the return of spontaneous circulation (ROSC) is often attained, very few patients survive to discharge. Patient characteristics, resuscitation success, overall mortality, and the cost of care did not differ between patients with and without ACP. However, patients with ACP had shorter hospital and intensive care unit (ICU) stays and higher rates of conversion to do-not-resuscitate (DNR) status post-resuscitation. Cardiopulmonary resuscitation (CPR) outcomes vary for patients with cancer. Here, we characterized cancer patients who underwent CPR in the emergency department (ED), their outcomes, and the effects of advanced care planning (ACP). The hospital databases and electronic medical records of cancer patients at a comprehensive cancer center who underwent CPR in the ED from 6 March 2016 to 31 December 2022 were reviewed for patient characteristics, return of spontaneous circulation (ROSC), conversion to do-not-resuscitate (DNR) status afterward, hospital and intensive care unit (ICU) length of stay, mortality, cost of hospitalization, and prior GOC discussions. CPR occurred in 0.05% of all ED visits. Of the 100 included patients, 67 patients achieved ROSC, with 15% surviving to hospital discharge. The median survival was 26 h, and the 30-day mortality rate was 89%. Patients with and without prior ACP had no significant differences in demographics, metastatic involvement, achievement of ROSC, or in-hospital mortality, but patients with ACP were more likely to change their code status to DNR and had shorter stays in the ICU or hospital. In conclusion, few cancer patients undergo CPR in the ED. Whether this results from an increase in terminally ill patients choosing DNR status requires further study. ACP was associated with increased conversion to DNR after resuscitation and decreased hospital or ICU stays without an increase in overall mortality. [ABSTRACT FROM AUTHOR]

Simple Summary: This research investigates the effectiveness and safety of totally implantable vascular access devices (TIVADs) used for delivering treatments such as chemotherapy. Over a five-year period, 70 patients received TIVADs through a standardized surgical method under local anesthesia. The study found very low complication rates, with only two notable incidents: one device needed adjustment due to a flipped catheter, and one infection occurred after over three years of use. The procedural success rate was 100%, with devices typically lasting around 22 months, and some even up to five years. These findings suggest that TIVADs are a reliable and safe option for long-term venous access, significantly benefiting routine clinical practices. Background: Daily clinical practice requires repeated and prolonged venous access for delivering chemotherapy, antibiotics, antivirals, parenteral nutrition, or blood transfusions. This study aimed to investigate the performance and the safety of totally implantable vascular access devices (TIVADs) over a 5-year follow-up period through a standardized well-trained surgical technique and patient management under local anesthesia. Methods: In a retrospective, observational, and monocentric study, 70 patients receiving POLYSITE® TIVADs for chemotherapy were included. The safety endpoints focused on the rate of perioperative, short-term, and long-term complications. The performance endpoints included vein identification for device insertion and procedural success rate. Results: The study demonstrated no perioperative or short-term complications related to the TIVADs. One (1.4%) complication related to device manipulation was identified as catheter flipping, which led to catheter adjustment 56 days post-placement. Moreover, one (1.4%) infection due to usage conditions was observed, leading to TIVAD removal 3 years and 4 months post-surgery. Catheter placement occurred in cephalic veins (71.4%), subclavian veins (20%), and internal jugular veins (8.6%). The procedural success rate was 100%. Overall, the implantable ports typically remained in place for an average of 22.4 months. Conclusions: This study confirmed the TIVADs' performance and safety, underscored by low complication rates compared to published data, thereby emphasizing its potential and compelling significance for enhancing routine clinical practice using a standardized well-trained surgical technique and patient management. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer is a major health concern worldwide, with mortality rates varying between ethnic groups. In Israel, Jewish and Muslim Arab women have different socioeconomic backgrounds and lifestyle factors that may influence breast cancer outcomes. This study investigates disparities in breast cancer mortality between these two groups and examines how factors such as number of children, socioeconomic status, and place of residence affect mortality rates. By analyzing data from over 800,000 Israeli women over a 30-year period, the researchers aim to understand the complex interplay among ethnicity, sociodemographic factors, and breast cancer mortality. The findings of this study could help identify key risk factors and protective elements specific to each ethnic group. This information is crucial for developing targeted intervention programs to reduce disparities and improve breast cancer outcomes for both Jewish and Muslim Arab women in Israel. Breast cancer mortality rates vary across ethnic groups in Israel, where protective factors such as high fertility and breastfeeding rates may be moderated by socioeconomic factors and mammography rates. We aim to investigate disparities in breast cancer mortality between Jewish and Muslim Arab women in Israel and examine how sociodemographic variables and number of children are associated with mortality. Our retrospective follow-up study uses data from the Israeli Central Bureau of Statistics and multivariable Cox regression models, adjusting for age, number of children, country of origin, locality size, and socioeconomic status. Compared to Jewish women, Muslim Arab women exhibited lower breast cancer mortality rates. However, after adjusting for multiple sociodemographic variables, no significant differences persisted between Jewish and Muslim Arab women. Having more than three children was associated with lower mortality among Muslim Arab women but not among Jewish women. European/American origin, larger localities, and medium socioeconomic status were associated with higher mortality. Sociodemographic factors may therefore explain the disparities in breast cancer mortality between Jewish and Muslim Arab women in Israel. Targeted intervention programs that consider the unique characteristics and risk factors of different ethnic groups are needed to reduce disparities and improve outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigated a new blood test (9G testTM Cancer/Lung) for early lung cancer detection. This test measures complexes of autoantibodies with specific lung cancer antigens for CYFRA 21-1 and p53. This study found that the diagnostic performances were significantly better than traditional methods at identifying LC, especially in early stages. The test showed good overall accuracy (AUC of 0.945) and detected early-stage lung cancer with high sensitivity (87.5%). This suggests it could be a valuable tool alongside existing scans like X-rays and LDCT for improving early LC detection. The early detection of lung cancer (LC) improves patient outcomes, but current methods have limitations. Autoantibodies against tumor-associated antigens have potential as early biomarkers. This study evaluated the 9G testTM Cancer/Lung, measuring circulating complexes of two antigen–autoantibody immune complexes (AIC) against their respective free antigens (CYFRA 21-1 and p53) for LC diagnosis. We analyzed 100 LC patients and 119 healthy controls using the 9G testTM Cancer/Lung, quantifying the levels of AICs (CYFRA 21-1-Anti-CYFRA 21-1 autoantibody immune complex (CIC) and p53-Anti-p53 autoantibody immune complex (PIC)), free antigens (CYFRA 21-1 and p53), and ratios of AICs/antigens (LC index). The levels of the CICs and PICs were significantly elevated in LC compared to the controls (p < 0.0062 and p < 0.0026), while free antigens showed no significant difference. The CIC/CYFRA 21-1 and PIC/p53 ratios were also significantly higher in LC (all, p < 0.0001). The LC index, when combining both ratios, exhibited the best diagnostic performance with an area under the curve (AUC) of 0.945, exceeding individual CICs, PICs, and free antigens (AUCs ≤ 0.887). At a cut-off of 3.60, the LC index achieved 81% sensitivity and 95% specificity for LC diagnosis. It detected early-stage (Stage I–II) LC with 87.5% sensitivity, exceeding its performance in advanced stages (72.7%). The LC index showed no significant differences based on age, gender, smoking status (former, current, or never smoker), or pack years smoked. The LC index demonstrates promising potential for early LC diagnosis, exceeding conventional free antigen markers. [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 retrospective database review of Danish real-world patients with asymptomatic melanoma brain metastases (MBM) treated with first-line ipilimumab and nivolumab demonstrates a similar complete response (CR), Progression-Free Survival (PFS), and overall survival (OS) rates when compared to previously published phase II trials. Combination immunotherapy using ipilimumab/nivolumab is the golden standard treatment for patients with melanoma and asymptomatic brain metastases (MBM). However, it remains uncertain if real-world patients have the same treatment effects compared to patients enrolled in clinical trials. The aim of this study was to compare clinical benefits between real-world patients and patients enrolled in clinical trials when administering ipilimumab/nivolumab in treatment-naive patients with asymptomatic MBM. Using data from the Danish Metastatic Melanoma Database (DAMMED), 79 patients with clinical parameters similar to the inclusion criteria from two phase II trials, the ABC and the CheckMate-204 trials, were included in the analyses. Thirteen patients (16.5%) achieved complete response (CR) and an overall response rate (ORR) of 46.9%. We found an overall 6-month Progression-Free Survival (PFS) rate of 53.5% and a median PFS of 6.5 months. Median overall survival (mOS) was not reached during the 5-year follow-up. These results were comparable to the phase II trials. In conclusion, clinical benefits from phase II studies were comparable to Danish real-world data regarding OS, PFS, and CR. Confirming that combination immunotherapy can be recommended as first-line treatment for patients with asymptomatic, treatment-naive melanoma brain metastases. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer care is being increasingly driven by biomarker testing. Many biomarkers are traditionally measured on a sample from a patient tumor such as a biopsy. More recently, "liquid biopsy" has emerged as a blood test to complement or replace traditional tissue-based testing. In this report, we explore one of the first case series of rapid liquid biopsy performed within a hospital setting. The results include a median 3-day time to results, compared to approximately 14 days using traditional centralized reference labs. Additional details of the cohort are shared to highlight the utility of point of care liquid biopsy. Liquid biopsy is rapidly becoming an indispensable tool in the oncologist's arsenal; however, this technique remains elusive in a publicly funded healthcare system, and real-world evidence is needed to demonstrate utility and feasibility. Here, we describe the first experience of an in-house point of care liquid biopsy program at a Canadian community hospital. A retrospective review of consecutive cases that underwent plasma-based next-generation sequencing (NGS) was conducted. Liquid biopsy was initiated at the discretion of clinicians. Sequencing followed a point of care workflow using the Genexus™ integrated sequencer and the Oncomine precision assay, performed by histotechnologists. Results were reported by the attending pathologist. Eligible charts were reviewed for outcomes of interest, including the intent of the liquid biopsy, results of the liquid biopsy, and turnaround time from blood draw to results available. A total of 124 cases, with confirmed or suspected cancer, underwent liquid biopsy between January 2021 and November 2023. The median turnaround time for liquid biopsy results was 3 business days (range 1–12 days). The sensitivity of liquid biopsies was 71%, compared to tissue testing in cases with matched tissue results available for comparison. Common mutations included EGFR (29%), in 86 lung cancer patients, and PIK3CA (22%), identified in 13 breast cancer patients. Healthcare providers ordered liquid biopsies to inform diagnostic investigations and treatment decisions, and to determine progression or resistance mechanisms, as these reasons often overlapped. This study demonstrates that rapid in-house liquid biopsy using point of care methodology is feasible. The technique facilitates precision treatment and offers many additional advantages for cancer care. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aimed to determine the risk and rate of development of overall and site-specific cancer in patients with type 2 diabetes mellitus compared with non-diabetic individuals. In this retrospective cohort study, excess incidence of cancer was found in patients with type 2 diabetes mellitus. While the incidence of cancer decreased in non-diabetic controls between 2015 and 2019 in most age groups and for several cancer sites, this decrease was less significant among patients with type 2 diabetes mellitus. Therefore, the results of this study demonstrate that the presence of type 2 diabetes mellitus leads to a higher incidence of cancer. (1) Background: Among the chronic complications of type 2 diabetes mellitus, cancer has become the leading cause of death in several countries. Our objective was to determine whether prevalent type 2 diabetes mellitus is associated with a higher incidence of cancer. (2) Methods: This study comprised a nationwide analysis conducted in Hungary. The study population was divided into two groups: a type 2 diabetes mellitus group vs. a non-diabetic group. The primary outcome was the risk related to overall cancer incidence; a key secondary outcome was the overall incidence of cancer in distinct study years; and a further outcome was the annual percent changes. (3) Results: The odds ratio related to the overall incidence of cancer was 2.50 (95% confidence interval: 2.46–2.55, p < 0.0001) in patients with diabetes as related to non-diabetic controls. The odds ratio was higher in males than in females [ORmales: 2.76 (2.70–2.82) vs. ORfemales: 2.27 (2.22–2.33), p < 0.05 for male-to-female comparison]. The annual cancer incidence rate declined in non-diabetic controls, but not in patients with diabetes [−1.79% (−2.07–−1.52%), p < 0.0001] vs. −0.50% (−1.12–+0.10%), p = 0.0991]. Several types of cancer showed a decreasing tendency in non-diabetic controls, but not in patients with type 2 diabetes. (4) Conclusions: Type 2 diabetes is associated with a higher risk of cancer. While the cancer incidence decreased for non-diabetic individuals with time, it remained unchanged in patients with T2DM. [ABSTRACT FROM AUTHOR]

Simple Summary: Endometrial endometrioid carcinoma (EEC) is generally considered to have a good prognosis. However, a subset of patients die of their disease. For this reason, it is essential to reveal and define all prognostic factors that can guide optimal treatment. Because lymphovascular space invasion (LVSI) is now related to staging, and blood vascular invasion seems to be more important than lymphovascular invasion, it could be important to encourage pathologists to distinguish between the two. The morphologic pattern of myometrial invasion may also be related to biological behavior. Myometrial invasion with an infiltrative pattern is associated with advanced-stage LVSI and recurrence. A specific pattern of myometrial invasion characterized by microcystic, elongated, and fragmented (MELF) glands is known to be associated with LVSI and lymph node metastases. This study investigated the relationship between these three closely related parameters, particularly the importance of blood vessel invasion (BVI), lymphatic vessel invasion (LVI), and MELF invasion as prognostic factors for endometrial cancer. This may be of great importance for the therapeutic approach in EEC. We studied 115 cases of EEC diagnosed on hysterectomy specimens. Double immunohistochemical staining (D2-40/CD31) was performed in all 115 cases to show LVI and BVI on the same slide. MELF pattern invasion was present in 24/115 (21%) cases. MELF-positive tumors had a higher frequency of LVI than MELF-negative tumors (58% and 23%, respectively); the frequency of BVI was twice as high in MELF-positive tumors in comparison to MELF-negative tumors (25% and 12%, respectively). These differences were significant (p ˂ 0.0001). All tumors with positive BVI also had a concomitant LVI. The presence of MELF invasion had no impact on overall survival, confirming previous studies. 5-year survival rates were almost equal in cases with negative LVSI and cases with positive isolated LVI (98% vs. 97%). However, in cases where BVI was also present, the 5-year survival rate was significantly lower, 63% (p ˂ 0.0001). Furthermore, BVI proved to be an independent prognostic factor for overall survival, disease-free survival, and recurrence in the multivariate analysis. In conclusion, MELF pattern invasion is a good predictor of lymphatic and blood vessel invasion but has no prognostic value. Our results suggest that BVI in EEC has greater clinical value than isolated LVI or myometrial invasion patterns, and the therapeutic approach should be guided by BVI presence. Therefore, we hope this study will promote the routine evaluation of BVI in the context of EEC diagnostic procedures. [ABSTRACT FROM AUTHOR]

Simple Summary: The incidence of multiple primary cancers (MPCs) among 96,174 cancer patients at the Korea Cancer Center Hospital (KCCH) from 2003 to 2022 was 2.3%. Breast cancer (15.7%) was the most common primary cancer, with lung cancer (15.2%) being the most frequent second primary cancer. The median latency period for second primary cancers was 4.1 years, decreasing for third and fourth primary cancers (2.1 years and 1.6 years, respectively). Lymphoma had the highest relative risk (2.1) for developing MPCs. Specific primary cancers showed significant associations with subsequent cancers, informing future research and management strategies. Rising cancer survival rates have led to an increased risk of multiple primary cancers (MPCs). Data on MPCs in South Korea are limited. This study aimed to address incidence and clinical characteristics of MPCs in a single cancer center in Korea during a 20-year period. We retrospectively analyzed 96,174 cancer patients at the Korea Cancer Center Hospital between 2003 and 2022, identifying 2167 patients with metachronous MPCs based on Surveillance, Epidemiology, and End Results SEER criteria. We categorized patients by cancer type (15 major solid cancer groups and 3 major hematologic cancer groups), including pathological diagnosis, assessed latency periods, and relative risks (RRs) for developing MPCs. The overall MPC incidence was 2.3%. Breast cancer (15.7%) was the most common primary cancer, and lung cancer (15.2%) was the most frequent second primary cancer. The median latency period for second primary cancers was 4.1 years. Decreasing latency periods for third and fourth primary cancers were observed (2.1 years and 1.6 years, respectively). Most cancers maintained their dominant pathological type despite notable changes in the prevalence of specific pathologies for certain types of second primaries. Lymphoma showed the highest RR (2.1) for developing MPCs. Significant associations were found between specific primary and subsequent cancers, including breast–ovary, thyroid–breast, stomach–pancreas, colorectal–head and neck, lung–prostate, and lymphoma–myeloid neoplasms. These findings contribute to a better understanding of MPC occurrence. They can inform future research on their etiology and development of improved management strategies. [ABSTRACT FROM AUTHOR]

Simple Summary: Estimating the risk of postoperative complications is important for shared decision-making with the patient. This also helps multidisciplinary teams to plan preoperative management and postoperative care and predict duration of recovery. In this retrospective pilot study, we aim to evaluate the accuracy and reliability of the P-POSSUM and ACS-NSQIP surgical risk calculators in predicting postoperative complications in gynaecological–oncological (GO) robotic surgery (RS). We were able to demonstrate that the ACS-NSQIP risk tool showed 90% accuracy in prediction of five major complications and mortality. Purpose: In this retrospective pilot study, we aim to evaluate the accuracy and reliability of the P-POSSUM and ACS-NSQIP surgical risk calculators in predicting postoperative complications in gynaecological–oncological (GO) robotic surgery (RS). Methods: Retrospective data collection undertaken through a dedicated GO database and patient notes at a tertiary referral cancer centre. Following data lock with the actual post-op event/complication, the risk calculators were used to measure predictive scores for each patient. Baseline analysis of 153 patients, based on statistician advice, was undertaken to evaluate P-POSSUM and ACS-NSQIP validity and relevance in GO patients undergoing RS performed. Results: P-POSSUM reports on mortality and morbidity only; ACS-NSQIP reports some individual complications as well. ACS-NSQIP risk prediction was most accurate for venous thromboembolism (VTE) (area under the curve (AUC)-0.793) and pneumonia (AUC-0.657) and it showed 90% accuracy in prediction of five major complications (Brier score 0.01). Morbidity was much better predicted by ACS-NSQIP than by P-POSSUM (AUC-0.608 vs. AUC-0.551) with the same result in mortality prediction (Brier score 0.0000). Moreover, a statistically significant overestimation of morbidity has been shown by the P-POSSUM calculator (p = 0.018). Conclusions: Despite the limitations of this pilot study, the ACS-NSQIP risk calculator appears to be a better predictor of major complications and mortality, making it suitable for use by GO surgeons as an informed consent tool. Larger data collection and analyses are ongoing to validate this further. [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: Gorlin syndrome (GS) is a genetic disorder characterized by multiple basal cell carcinomas (BCCs) due to mutations in the hedgehog signaling pathway. Patients with GS may need dozens or even hundreds of surgical procedures in their lifetime, which can leave them severely scarred, deformed, and disfigured. In 16 patients with GS, we examined the effectiveness, safety, and length of response to oral hedgehog inhibitors. According to our retrospective study, sonidegib inhibited the growth of both newly diagnosed and pre-existing basal cell carcinomas more successfully and safely than vismodegib. Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome (GS), is a genetic disorder characterized by the development of multiple cutaneous BCCs due to mutations in the hedgehog signaling pathway. The use of hedgehog pathway inhibitors—vismodegib and sonidegib—has emerged as a promising therapeutic strategy for managing BCCs in individuals with GS. In a retrospective study conducted between March 2012 and January 2024, a cohort of 16 Gorlin syndrome patients who received treatment with either sonidegib or vismodegib were analyzed. The primary objectives of the study were to evaluate the efficacy, safety profile, and duration of response to oral hedgehog inhibitors in this patient population. The study assessed various parameters, including the number of new BCCs that developed before and after treatment initiation, the duration and sustainability of treatment responses, as well as the incidence of adverse effects associated with hedgehog inhibitor therapy. The findings of the study revealed that sustained treatment with hedgehog inhibitors could effectively suppress the progression of both new and existing BCCs. Furthermore, the results indicated that sonidegib exhibited superior efficacy and safety compared to vismodegib in the treatment of BCCs in individuals with GS. Notably, adjustments to the administration schedule of sonidegib were found to improve tolerability without compromising therapeutic efficacy, potentially leading to prolonged durations of treatment response and disease control. [ABSTRACT FROM AUTHOR]

Simple Summary: Most cancer patients are older and have concomitant diseases because the incidence of most cancer types increases with age. This leads to patients taking a variety of medications that can cause drug-related problems (DRPs). DRPs can cause harm, including increased illness, avoidable hospital stays, and even death. Common DRPs are drug–drug interactions, not taking medication as prescribed, and adverse drug reactions. In our study, we aimed to assess these medication risks in hospitalized cancer patients and to identify factors that influence their health-related quality of life (HRQOL) as a patient-relevant outcome. The results of the pharmacist-led medication reviews show that DRPs are common in hospitalized cancer patients. Therefore, patient questionnaires about therapy-related symptoms could improve the detection of DRPs. While drug-related factors had no effect on HRQOL during the hospital stay, our analysis revealed other influencing factors, such as relapse status of the cancer disease and length of hospital stay. Background: We aimed to assess medication risks and determine factors influencing the health-related quality of life (HRQOL) in cancer inpatients. Methods: A retrospective analysis was conducted to identify drug-related problems (DRPs) based on medication reviews, including patient-reported outcomes (PROs). Multiple linear regression analyses were performed to identify sociodemographic, disease-related, and drug therapy-related factors influencing changes from hospital admission to discharge in the scales of the EORTC QLQ-C30 questionnaire. Results: A total of 162 inpatients with various hematological and solid cancer diseases was analyzed. Patients received a mean of 11.6 drugs and 92.6% of patients exhibited polymedication resulting in a mean of 4.0 DRPs per patient. Based on PRO data, 21.5% of DRPs were identified. Multiple linear regression models described the variance of the changes in global HRQOL and physical function in a weak-to-moderate way. While drug therapy-related factors had no influence, relapse status and duration of hospital stay were identified as significant covariates for global HRQOL and physical function, respectively. Conclusion: This analysis describes underlying DRPs in a German cancer inpatient population. PROs provided valuable information for performing medication reviews. The multiple linear regression models for global HRQOL and physical function provided explanations for changes during hospital stay. [ABSTRACT FROM AUTHOR]

Simple Summary: Hepatocellular carcinoma (HCC) is a life-threatening disease of the liver. Patients who also have a blockage of the portal vein, which takes blood into the liver, are at particular risk for death. This condition is known as portal vein tumor thrombosis (PVTT). Proton beam therapy (PBT) is an excellent treatment option for tumors because it allows the tumor to be irradiated while avoiding radiation effects on normal tissue. In this study, we found that the long-term outcomes in patients with HCC with advanced PVTT (Vp3 or Vp4) were improved by treatment with PBT. In particular, the median survival time after was >20 months in patients treated with PBT for cure of the disease. These results are better than those with other therapies and suggest that PBT gives a survival benefit in these cases. There were also very few adverse events, indicating that PBT is a safe method. Hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) has a poor prognosis and is generally not indicated for surgery. Proton beam therapy (PBT) may offer an alternative treatment. In this study, long-term outcomes were examined in 116 patients (median age 66 years, 100 males) with HCC with advanced PVTT (Vp3 or Vp4) who received PBT from April 2008 to March 2018. Of these patients, 63 received PBT as definitive treatment and 53 as palliative treatment. The representative dose was 72.6 Gy (RBE) in 22 fractions. Eight patients died in follow-up, including 72 due to tumor progression. The 5-year overall survival (OS) rate was 18.0% (95% CI 9.8–26.2%) and the 5-year local control (LC) rate was 86.1% (74.9–97.3%). In multivariate analyses, performance status and treatment strategy were significantly associated with OS. The median follow-up period for survivors with definitive treatment was 33.5 (2–129) months, and the 5-year OS rate was 25.1% (12.9–37.3%) in these cases. The median survival time after definitive irradiation was >20 months. The 5-year OS rate was 9.1% (0–19.7%) for palliative irradiation. These results compare favorably with those of other therapies and suggest that PBT is a useful option for cases of HCC with advanced PVTT that cannot undergo surgery, with an expected survival benefit and good local control. Determining the optimal indication for this treatment is a future challenge. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aimed to explore the relationship of the pN stage of thyroid cancer (TC) and ultrasound hypoechogenicity with encapsulation and vascular invasion. A retrospective study involving 678 TC patients revealed that a greater pN stage was correlated with encapsulation and vascular invasion as well as with positive hypoechogenicity. These findings have significant prognostic and clinical implications for managing TC. Discovering these correlations confirms the importance of the TNM scale in stratifying TC patients based on disease severity. The results suggest that the hypoechoic patterns observed on thyroid ultrasound may serve as indicators of aggressive tumour behaviour and increased invasion risk. This analysis highlights diverse invasion patterns among TC patients, which may have significant clinical implications for diagnostic processes and treatment strategy selection. Further research is necessary to validate these findings and explore new biomarkers and imaging methods to refine TC staging systems and improve TC patient care. In this retrospective study, the relationship between the pN stage of TC and the ultrasound hypoechogenicity of tumour encapsulation and vascular invasion was investigated. The data of a total of 678 TC patients were analysed. The goal of this study was to assess the significance of the pTNM score and preoperative ultrasound features in predicting cancer prognosis and guiding therapeutic decisions in patients with TC. The main research methods included a retrospective analysis of patient data, mainly the pTNM score and presence of tumour encapsulation and vascular invasion obtained from histopathological results and preoperative ultrasound imaging. Patients with well-differentiated TCs (papillary and follicular) were extracted from TC patients to better unify the results because of similar clinical strategies for these TCs. Significant associations were observed between advanced pN stage and the presence of encapsulation and vessel invasion. The majority of pN1a patients exhibited encapsulation (77.71%; p < 0.0001) and vascular invasion (75.30%; p < 0.0001), as did the majority of pN1b patients (100%; p < 0.0001 and 100%; p < 0.0001, respectively). Less than half of the patients with hypoeghogenic patterns presented with encapsulation (43.30%; p < 0.0001) and vascular invasion (43.52%; p < 0.0001), while the vast majority of patients without hypoechogenicity did not present with encapsulation (90.97%; p < 0.0001) or vascular invasion (90.97%; p < 0.0001). Hypoechogenicity was found to be indicative of aggressive tumour behaviour. The results of this study underscore the importance of accurate N staging in TC and suggests the potential use of ultrasound features in predicting tumour behaviour. Further research is needed to confirm these findings and explore additional prognostic markers to streamline TC management strategies and improve patient outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: This research aims to evaluate the effectiveness of a machine learning algorithm, XGBoost, in predicting treatment recommendations for patients with hepatocellular carcinoma (HCC). The study uses clinical and imaging data from patients discussed at a multidisciplinary tumor board. The findings suggest that the algorithm can accurately predict all eight treatment recommendations made by the board, potentially aiding clinical decision-making in settings lacking subspecialty expertise. This study addresses the potential of machine learning in predicting treatment recommendations for patients with hepatocellular carcinoma (HCC). Using an IRB-approved retrospective study of patients discussed at a multidisciplinary tumor board, clinical and imaging variables were extracted and used in a gradient-boosting machine learning algorithm, XGBoost. The algorithm's performance was assessed using confusion matrix metrics and the area under the Receiver Operating Characteristics (ROC) curve. The study included 140 patients (mean age 67.7 ± 8.9 years), and the algorithm was found to be predictive of all eight treatment recommendations made by the board. The model's predictions were more accurate than those based on published therapeutic guidelines by ESMO and NCCN. The study concludes that a machine learning model incorporating clinical and imaging variables can predict treatment recommendations made by an expert multidisciplinary tumor board, potentially aiding clinical decision-making in settings lacking subspecialty expertise. [ABSTRACT FROM AUTHOR]

Simple Summary: This retrospective study focused on 23 patients diagnosed with Hepatocellular Carcinoma (HCC), utilizing the Liver Imaging Reporting and Data System (LI-RADS) for classification. This system aids in the non-invasive diagnosis of HCC, potentially eliminating the need for a diagnostic biopsy. Patients were selected based on their diagnosis, confirmed either via imaging methods that identified advanced liver nodules or via histopathological findings consistent with HCC, including specific protein markers. The study aimed to assess the histopathological changes resulting from prior local interventions, such as trans-arterial chemoembolization or radiofrequency ablation, and their impact on the tumor's response to subsequent immune therapies. Key findings indicated variations in alpha-fetoprotein levels and increased expression of the immune marker PD-L1 in untreated patients, suggesting a more aggressive cancer progression in these individuals. The study's conclusions support the use of liver biopsy in refining therapeutic approaches for HCC, particularly in recurrent cases post-intervention, to enhance personalized immune therapy strategies. Background: The Liver Imaging Reporting and Data System (LI-RADS) combines standardized terminology with a classification system for imaging findings in patients with HCC, therefore rendering diagnostic biopsy unnecessary in many cases. This retrospective study included 23 patients with a biopsy diagnosis of HCC, performed either before or after local interventional procedures, in order to evaluate the histopathologic changes induced by previous procedures and their potential influence on the response to immune therapy. Material and Methods: The study encompassed a cohort of patients diagnosed with Hepatocellular Carcinoma (HCC). Diagnosis was established via contrast-enhanced computer tomography or magnetic resonance imaging that identified LI-RADS-5 nodules in conjunction with historical liver disease and elevated alpha-fetoprotein (AFP) levels or via histological examination confirming positivity for glypican3, heat shock protein 70, and glutamine synthetase. The study detailed the liver disease etiology, LI-RADS scores, characteristics and dimensions of HCC nodules, serum AFP concentrations, Edmondson–Steiner grading, and the expression of programmed cell death ligand 1 (PD-L1) in the tumor cells. Results: Among the study's cohort of Hepatocellular Carcinoma (HCC) patients, a portion had not received any prior treatments, while the remainder experienced local HCC recurrence following trans-arterial chemoembolization or radiofrequency ablation. Observations indicated elevated alpha-fetoprotein (AFP) levels in those who had not undergone any previous interventions, showing statistical significance. The Edmondson–Steiner classification predominantly identified grade III differentiation across patients, irrespective of their treatment history. Furthermore, an increase in intra-tumoral programmed cell death ligand 1 (PD-L1) expression was noted in patients who had not been subjected to previous therapies. Conclusion: Liver biopsy offers valuable insights for patients with Hepatocellular Carcinoma (HCC), assisting in the tailoring of immune therapy strategies, particularly in cases of recurrence following prior local interventions. [ABSTRACT FROM AUTHOR]

Simple Summary: Corticosteroid use for the treatment of immune related adverse events (irAEs) after immune checkpoint inhibitor (ICI) use comes with concerns of side effects and the potential abrogation of antitumor immunity. Relatedly, the impact of steroid-sparing immunosuppressive agents (SSIAs) for treatment of irAEs on tumor outcomes is not well known, and current literature on this topic is limited by study design and issues around immortal time bias. This retrospective case-control study accounts for immortal time bias via strategic statistical methodology. Our results suggest that SSIAs used for irAE treatment may not negatively impact cancer outcomes in malignant melanoma and non-small cell lung cancer. For patients with melanoma, our results demonstrated better progression free survival for patients treated with infliximab compared to patients treated with corticosteroid monotherapy for irAEs. This study supports the safety for utilizing SSIAs for irAE treatment in patients receiving immune checkpoint inhibitors. Our study also encourages accounting for immortal time bias in the design of other observational studies in this space to accurately convey results and draw clinically meaningful conclusions. Background: The effects of steroid-sparing immunosuppressive agents (SSIAs), used for the treatment of immune-related adverse events (irAEs), on immune checkpoint inhibitor (ICI) antitumor activity is not well known. We compared tumor outcomes of patients who received corticosteroid monotherapy (CS) versus a corticosteroid plus SSIA (CS-SSIA) for irAE treatment, using statistical methods to address immortal time bias. Methods: We conducted a retrospective case-control study on patients ≥ 18 years with melanoma or non-small-cell lung cancer (NSCLC) treated with ≥1 ICI at a quaternary care center between 1 January 2016 and 11 January 2021. Patients were divided into two cohorts: CS or CS-SSIA. We used propensity score nearest-neighbor matching to match on tumor type, stage, and prior lines of therapy. Primary outcomes were progression-free survival (PFS) and overall survival (OS). Secondary outcomes included the time from the start of the irAE treatment to the irAE resolution. Hazard ratios (HRs) for PFS and OS were calculated using the Cox proportional hazard regression method with both (1) the time to the steroid and SSIA as time-varying covariates and (2) a binary exposure classification not accounting for the time to the treatment. Results: A total of 167 patients were included after matching (132 in the CS cohort and 35 in the CS-SSIA cohort). Sixty-six percent of all the patients had melanoma. The most common irAEs requiring treatment were gastroenterocolitis and hepatitis. In an adjusted analysis not accounting for immortal time bias, there were no significant differences in PFS (HR 0.75, 95% CI [0.46–1.23]) or OS (HR 0.82, 95% CI [0.46–1.47]). In analyses using a time-varying treatment indicator, there was a trend toward improved PFS in patients treated with SSIAs (HR 0.54, CI 0.26–1.10). There was no difference in OS (HR 1.11, CI 0.55–2.23). Patients with melanoma who specifically received infliximab had improved PFS compared to patients with CS only, after adjusting for immortal time bias (HR 0.32, CI 0.24–0.43). Conclusions: The use of SSIAs with CS did not have worse outcomes than CS monotherapy. In melanoma, our findings showed improved PFS for the use of infliximab versus steroid monotherapy for irAEs. Large, prospective, randomized controlled trials are needed to confirm these findings and guide the optimal treatment of irAEs. [ABSTRACT FROM AUTHOR]

Simple Summary: This study examines the viability of liver grafts from donors aged 85 years and older in liver transplantation (LT) compared to those from younger donors under 40 years old. The research, conducted on data from 2005 to 2023, evaluates post-LT outcomes using propensity score matching. Despite lower 5-year survival rates in the elderly group before matching, the proposed nomogram provides a more acceptable 10-year post-LT survival using grafts from older donors. Notably, the study emphasizes the importance of proper matching, particularly for recipients with hepatocellular carcinoma (HCC), in achieving satisfactory long-term results amid organ scarcity. Background: Despite the ongoing trend of increasing donor ages in liver transplantation (LT) setting, a notable gap persists in the availability of comprehensive guidelines for the utilization of organs from elderly donors. This study aimed to evaluate the viability of livers grafts from donors aged ≥85 years and report the post-LT outcomes compared with those from "ideal" donors under 40 years old. Methods: Conducted retrospectively at a single center from 2005 to 2023, this study compared outcomes of LTs from donors aged ≥85 y/o and ≤40 y/o, with the propensity score matching to the recipient's gender, age, BMI, MELD score, redo-LT, LT indication, and cause of donor death. Results: A total of 76 patients received grafts from donors ≥85 y/o and were compared to 349 liver grafts from donors ≤40 y/o. Prior to PSM, the 5-year overall survival was 63% for the elderly group and 77% for the young group (p = 0.002). After PSM, the 5-year overall survival was 63% and 73% (p = 0.1). A nomogram, developed at the time of graft acceptance and including HCC features, predicted 10-year survival after LT using a graft from a donor aged ≥85. Conclusions: In the context of organ scarcity, elderly donors emerge as a partial solution. Nonetheless, without proper selection, LT using very elderly donors yields inferior long-term outcomes compared to transplantation from very young donors ≤40 y/o. The resulting nomogram based on pre-transplant criteria allows for the optimization of elderly donor/recipient matching to achieve satisfactory long-term results, in addition to traditional matching methods. [ABSTRACT FROM AUTHOR]

Simple Summary: Sex differences in cancer are well-established. However, less is known about sex differences in the diagnosis of brain metastasis and outcomes among patients with advanced melanoma. Using the nationwide Flatiron Health electronic health record-derived de-identified database, this study showed that males had greater odds of brain metastasis, and poorer real-world overall survival compared to females among those with brain metastasis, while there were no sex differences in clinical outcomes for those with advanced melanoma without brain metastasis. Sex differences in cancer are well-established. However, less is known about sex differences in diagnosis of brain metastasis and outcomes among patients with advanced melanoma. Using a United States nationwide electronic health record-derived de-identified database, we evaluated patients diagnosed with advanced melanoma from 1 January 2011–30 July 2022 who received an oncologist-defined rule-based first line of therapy (n = 7969, 33% female according to EHR, 35% w/documentation of brain metastases). The odds of documented brain metastasis diagnosis were calculated using multivariable logistic regression adjusted for age, practice type, diagnosis period (pre/post-2017), ECOG performance status, anatomic site of melanoma, group stage, documentation of non-brain metastases prior to first-line of treatment, and BRAF positive status. Real-world overall survival (rwOS) and progression-free survival (rwPFS) starting from first-line initiation were assessed by sex, accounting for brain metastasis diagnosis as a time-varying covariate using the Cox proportional hazards model, with the same adjustments as the logistic model, excluding group stage, while also adjusting for race, socioeconomic status, and insurance status. Adjusted analysis revealed males with advanced melanoma were 22% more likely to receive a brain metastasis diagnosis compared to females (adjusted odds ratio [aOR]: 1.22, 95% confidence interval [CI]: 1.09, 1.36). Males with brain metastases had worse rwOS (aHR: 1.15, 95% CI: 1.04, 1.28) but not worse rwPFS (adjusted hazard ratio [aHR]: 1.04, 95% CI: 0.95, 1.14) following first-line treatment initiation. Among patients with advanced melanoma who were not diagnosed with brain metastases, survival was not different by sex (rwOS aHR: 1.06 [95% CI: 0.97, 1.16], rwPFS aHR: 1.02 [95% CI: 0.94, 1.1]). This study showed that males had greater odds of brain metastasis and, among those with brain metastasis, poorer rwOS compared to females, while there were no sex differences in clinical outcomes for those with advanced melanoma without brain metastasis. [ABSTRACT FROM AUTHOR]

Simple Summary: Colorectal cancer is one of the most commonly diagnosed cancers worldwide with a high probability of developing metastasis over the course of the disease. Only certain patients with colorectal liver metastases can be treated by surgical resection. Different interventional treatments such as laser-induced thermotherapy, microwave ablation, as well as transarterial chemoembolization can be applied for treating colorectal liver metastases. These therapies have been discussed in various studies. However, the current medical literature is still lacking research from large long-term studies. This retrospective monocentric study includes 2140 patients with colorectal liver metastases treated by different locoregional treatments. It is based upon data collected over a period of more than 26 years at the University Hospital Frankfurt of Goethe University. The aim of this study was to analyze the long-term results of different locoregional treatments for colorectal cancer liver metastases (CRLM), including transarterial chemoembolization (TACE), laser-induced thermotherapy (LITT) and microwave ablation (MWA). A total of 2140 patients with CRLM treated at our department between 1993 and 2020 were included in this retrospective study. The patients were divided into the following groups: LITT (573 patients; median age: 62 years), TACE + LITT (346 patients; median age: 62 years), MWA (67 patients; median age: 59 years), TACE + MWA (152 patients; median age: 65 years), and TACE (1002 patients; median age: 62 years). Median survival was 1.9 years in the LITT group and 1.7 years in the TACE + LITT group. The median survival times in the MWA group and TACE + MWA group were 3.1 years and 2.1 years, respectively. The median survival in the TACE group was 0.8 years. The 1-, 3-, and 5-year survival rates were 77%, 27%, and 9% in the LITT group and 74%, 18%, and 5% in the TACE + LITT group, respectively. The corresponding survival rates were 80%, 55%, and 33% in the MWA group, 74%, 36%, and 20% in the TACE + MWA group and 37%, 3%, and 0% in the TACE group, respectively. The long-term results of this study demonstrate the efficacy of locoregional treatments in treating patients with CRLM. The longest survival was found in the MWA group, followed by the combination therapy of TACE and MWA. [ABSTRACT FROM AUTHOR]

Simple Summary: Newly diagnosed type 2 diabetes mellitus is associated with a higher risk of cancer, possibly in young individuals with diabetes. While the incidence of cancer is mildly decreasing in the background population, it does not decrease in patients with type 2 diabetes. In non-diabetic persons, certain types of cancer also occur in young age, while the 60–69-year-old group dominates for cancer cases in patients with type 2 diabetes. The majority of the new cancer cases is recognized within 6 months after the diagnosis of diabetes. This may call for increased cancer surveillance in patients with newly diagnosed type 2 diabetes mellitus. (1) Background: Patients with type 2 diabetes mellitus (T2DM) are at higher risk of cancer but how these two diseases associate is still debated. The goal of this study was the assessment of the overall incidence of cancer among patients with newly diagnosed T2DM in Hungary. (2) Methods: A nationwide, retrospective, longitudinal study was performed using a Hungarian database. After exclusion of cases of age < 18 years, with gestational diabetes, with polycystic ovary syndrome, and with type 1 and prevalent type 2 diabetes mellitus, the incident T2DM (approx. 50,000 cases yearly) and for comparison, the diabetes-free Hungarian adult population (approx. 7,000,000 cases yearly) was included in the study. The primary endpoints were the overall and site-specific incidence and annual percentage change of the incidence of cancer in both populations. (3) Results: The overall incidence of cancer in patients amounted to 29.4/1000 and 6.6/1000 with or without T2DM, respectively, and the OR (95%CI) of cancer of the T2DM group was 4.32 (4.14–4.53), p < 0.0001. The risk of having cancer was age dependent. The incidence of cancer was declining in the non-diabetic but was unchanged in the T2DM population. The average lag time of diagnosing cancer after the detection of T2DM was 3.86 months. (4) Conclusions: Incident T2DM is associated with a significantly higher overall risk of incident cancer, with a reverse correlation of age. Newly registered T2DM patients were suggested to be screened for cancer within 6 months. [ABSTRACT FROM AUTHOR]

Simple Summary: This is a retrospective national cohort study that aims to assess the risk of developing pancreatic cancer in patients with type 2 diabetes mellitus (T2DM) who are being treated with Glucagon-like Peptide-1 receptor agonists. We exclude patients with multiple risk factors for pancreatic cancer from our study. We retrospectively follow the patients for 7 years after the initiation of treatment. Current evidence is controversial about their use and the possible risk of pancreatic disease. We aim to revoke the association of pancreatic cancer with their use in support of their continued use due to their beneficial cardiovascular and renal effects. Background: GLP-1 RAs are widely used for T2DM treatment due to their cardiorenal and metabolic benefits. This study examines the risk of pancreatic cancer with GLP-1 RA use in patients with T2DM. Methods: We analyzed TriNetX's deidentified research database using the U.S. Collaborative Network comprising 62 healthcare organizations across the U.S.A. Patients with T2DM were split into two cohorts: one receiving GLP-1 RAs, and one not receiving GLP-1 RAs. We excluded patients with known risk factors for pancreatic cancer, including pancreatic cysts, a personal or family history of BRCA1, BRCA2, CDKN2A, KRAS, MEN1, MLH1, MSH2, NOTCH1, PALB2, PMS2, and PRSS1S genes, family history of pancreatic cancer, and VHL syndrome. Using a 1:1 propensity score-matching model based on baseline characteristics and comorbidities, we created comparable cohorts. We then compared the rate of pancreatic cancer between the two cohorts at a 7-year interval. Results: Out of 7,146,015 identified patients with T2DM, 10.3% were on a GLP-1 RA and 89.7% were not. Post-PSM, 721,110 patients were in each group. Patients on GLP-1 RAs had a 0.1% risk compared to a 0.2% risk of pancreatic cancer in the 7-year timeframe. Conclusion: The use of GLP-1 RAs in patients with type 2 diabetes mellitus (T2DM) does not appear to substantially elevate the risk of pancreatic cancer; in fact, it may potentially exert a protective effect. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, we investigate the availability and access to orphan drugs for rare cancers in Bulgaria, aiming to address the urgent need for improved treatment access for this vulnerable population. By comparing data from European and national sources, we aimed to assess the availability, delays, and budgetary impact of these drugs. Our findings reveal significant disparities in their access and highlight the pressing need for targeted policies to address these inequalities. This research contributes valuable insights into the challenges faced by rare cancer patients and we call for focused efforts at both the European and national levels to ensure equitable access to treatment. Rare cancers are defined by an annual incidence of fewer than 6 per 100,000. Bearing similarities to rare diseases, they are associated with substantial health inequalities due to diagnostic complexity and delayed access to innovative therapies. This situation is further aggravated in Southeastern European countries like Bulgaria, where limited public resources and expertise underscore the need for additional policy and translational research on rare cancers. This study aimed to explore the availability and access to orphan drugs for rare cancers in Bulgaria for the period of 2020–2023. We cross-compared data from both the European Union and national public sources to evaluate the number of available and accessible orphan drugs for rare cancers, the delay from market authorization to reimbursement, the dynamics of public expenditures, and regional disparities in access across the country. We juxtaposed the main characteristics of oncological and non-oncological orphan drugs as well. Only 15 out of 50 oncological orphan drugs that were authorized by the European Medicine Agency were accessible for rare cancer patients in Bulgaria. The median delay between market authorization and inclusion in the Bulgarian Positive Drug List was 760 days. The total expenditures for all orphan drugs for rare cancers amounted to EUR 74,353,493 from 2020 to 2023. The budgetary impact of this group rose from 0.24% to 3.77% of total public medicinal product expenditures for the study period. Rare cancer patients represent a vulnerable population that often faces limited to no access to treatment. We call for targeted European and national policies to address this major inequality. [ABSTRACT FROM AUTHOR]

Simple Summary: The prevalence of second neoplasms among patients with hairy cell leukemia (HCL) treated with cladribine is not negligible. Immunosuppression, high rate of cure, and aging may have a role in the pathogenesis of second cancers after HCL. We aimed to compare the risk of cancer between patients with HCL treated with cladribine and the general population. Concern has emerged about the prevalence of second cancers among patients with hairy cell leukemia (HCL) treated with purine analogs. We investigated 513 patients with HCL treated with cladribine over the last 30 years at 18 Italian centers and calculated their standardized incidence ratios (SIRs). We identified 24 patients with a second cancer diagnosed at a median time from treatment with cladribine of 59.9 months (range: 9.2–169.7 months). All patients with solid neoplasms presented with a limited-stage disease, except four cases of locally advanced cancer; multiple myeloma patients had a smoldering disease, while lymphoma patients had stage Ie and stage IV diseases. Response to therapy was complete in 19 cases; 1 patient is still receiving treatment for a relapsing bladder disease, while 2 patients progressed during treatment and died. These two patients died from unrelated causes: one from infection and one due to surgery complications. The median OS from HCL was 98.5 months (range: 38.4–409.2 months), while the median OS from second cancer was 27.6 months (range: 1–117.8 months). The SIR was 0.86 (95% CI: 0.54–1.30) for males and 1.13 (95% CI: 0.36–2.73) for females: no statistically significant differences were highlighted. We were not able to demonstrate an excess of second cancer or a significant association with the specific studied neoplasm. [ABSTRACT FROM AUTHOR]

Simple Summary: This clinical study explored the use of the positron emission tomography radiotracer, [18F]FSPG, for cancer imaging. [18F]FSPG measures a process involved in antioxidant production, which is important for cancer prognosis. We compared the distribution of this imaging agent in subjects with head and neck squamous cell cancer (HNSCC) and non-small-cell lung cancer (NSCLC). Results showed similar distribution in healthy organs but varied uptake in tumors, both between subjects and across different lesions. Although [18F]FSPG PET/CT offers insights into individual tumor behavior, its diagnostic potential is limited due to this variability in tumor uptake. Variability in [18F]FSPG retention, however, may provide crucial information about how tumors respond to therapy and mechanisms of treatment resistance. Background: (4S)-4-(3-[18F]fluoropropyl)-L-glutamic acid ([18F]FSPG) positron emission tomography/computed tomography (PET/CT) provides a readout of system xc− transport activity and has been used for cancer detection in clinical studies of different cancer types. As system xc− provides the rate-limiting precursor for glutathione biosynthesis, an abundant antioxidant, [18F]FSPG imaging may additionally provide important prognostic information. Here, we performed an analysis of [18F]FSPG radiotracer distribution between primary tumors, metastases, and normal organs from cancer patients. We further assessed the heterogeneity of [18F]FSPG retention between cancer types, and between and within individuals. Methods: This retrospective analysis of prospectively collected data compared [18F]FSPG PET/CT in subjects with head and neck squamous cell cancer (HNSCC, n = 5) and non-small-cell lung cancer (NSCLC, n = 10), scanned at different institutions. Using semi-automated regions of interest drawn around tumors and metastases, the maximum standardized uptake value (SUVmax), SUVmean, SUV standard deviation and SUVpeak were measured. [18F]FSPG time–activity curves (TACs) for normal organs, primary tumors and metastases were subsequently compared to 18F-2-fluoro-2-deoxy-D-glucose ([18F]FDG) PET/CT at 60 min post injection (p.i.). Results: The mean administered activity of [18F]FSPG was 309.3 ± 9.1 MBq in subjects with NSCLC and 285.1 ± 11.3 MBq in those with HNSCC. The biodistribution of [18F]FSPG in both cohorts showed similar TACs in healthy organs from cancer patients. There was no statistically significant overall difference in the average SUVmax of tumor lesions at 60 min p.i. for NSCLC (8.1 ± 7.1) compared to HNSCC (6.0 ± 4.1; p = 0.29) for [18F]FSPG. However, there was heterogeneous retention between and within cancer types; the SUVmax at 60 min p.i. ranged from 1.4 to 23.7 in NSCLC and 3.1–12.1 in HNSCC. Conclusion: [18F]FSPG PET/CT imaging from both NSCLC and HNSCC cohorts showed the same normal-tissue biodistribution, but marked tumor heterogeneity across subjects and between lesions. Despite rapid elimination through the urinary tract and low normal-background tissue retention, the diagnostic potential of [18F]FSPG was limited by variability in tumor retention. As [18F]FSPG retention is mediated by the tumor's antioxidant capacity and response to oxidative stress, this heterogeneity may provide important insights into an individual tumor's response or resistance to therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Myelofibrosis is a rare bone marrow disorder, leading to an increasing failure to generate healthy blood cells. Defining clinical prognosis scores for rare diseases is difficult, as sufficient numbers of patients for score validation are difficult to obtain. The current study investigates the utility of the TriNetX database, containing electronic medical records for over 140 million patients, to identify risk factors and establish clinical scores. TriNetX includes more than 64,000 myelofibrosis patients, and the present study explores factors influencing survival and common complications. Age over 65, anemia, an increased number of leukocytes, a low platelet count and an increased number of monocytes are associated with increased risks, while high numbers of eosinophiles and basophiles show positive associations. We demonstrate that the TriNetX database offers insights to refine predictive models, crucial for tailoring treatments to individual patient risks in the complex landscape of rare diseases like myelofibrosis. Myelofibrosis (MF) is a myeloproliferative neoplasia arising de novo as primary myelofibrosis (PMF) or secondary to polycythemia vera or essential thrombocythemia. Patients experience a high symptom burden and a marked reduction in life expectancy. Despite progress in molecular understanding and treatment, the clinical and prognostic heterogeneity of MF complicates treatment decisions. The International Prognostic Scoring System (IPSS) integrates clinical factors for risk stratification in MF. This study leverages the TriNetX database with more than 64,000 MF patients to assess the impact of accessible parameters on survival and complicating events, including AML transformation, cachexia, increased systemic inflammation, thrombosis and hemorrhage. Age over 65 years correlated with increased risks of death, AML transformation, thrombosis and hemorrhage. Anemia (Hb < 10 g/dL), leukocytosis (>25 × 103/µL) and thrombocytopenia (<150 × 103/µL) reduced survival and increased risks across all assessed events. Monocytosis is associated with decreased survival, whereas eosinophilia and basophilia were linked to improved survival. Further, as proof of concept for the applicability of TriNetX for clinical scores, we devised a simplified IPSS, and confirmed its value in predicting outcomes. This comprehensive study underscores the importance of age, anemia, leukocytosis and thrombocytopenia in predicting disease trajectory and contributes to refining prognostic models, addressing the challenges posed by the disease's heterogeneity. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigates the impact of an outpatient palliative care program on the location of death among patients with cancer. The findings reveal a notable increase in home and hospice deaths for those participating in the program, highlighting the potential benefits of specialized palliative care in challenging healthcare contexts. While the positive impact of early palliative care on the quality of life of cancer patients is well established, there is a noticeable research gap in developing countries. This study sought to determine the impact of an outpatient palliative care (OPC) program on the location of death among patients in Brazil. This was a retrospective study including patients with cancer who died between January 2022 and December 2022 in 32 private cancer centers in Brazil. Data were collected from medical records, encompassing demographics, cancer characteristics, and participation in the OPC program. The study involved 1980 patients, of which 32.3% were in the OPC program. OPC patients were predominantly younger (average age at death of 66.8 vs. 68.0 years old, p = 0.039) and composed of women (59.4% vs. 51.3%, p = 0.019) compared to the no-OPC patients. OPC patients had more home/hospice deaths (19.6% vs. 10.4%, p < 0.001), and participation in the outpatient palliative care program strongly predicted home death (OR: 2.02, 95% CI: 1.54–2.64). Our findings suggest a significant impact of the OPC program on increasing home and hospice deaths among patients with cancer in our sample. These findings emphasize the potential of specialized OPC programs to enhance end-of-life care, particularly in low-resource countries facing challenges related to social and cultural dimensions of care and healthcare access. [ABSTRACT FROM AUTHOR]

Simple Summary: The clinical course of classic Hodgkin lymphoma arising in immune deficiency/dysregulation (CHL-IDD) differs from that of CHL arising in immunocompetent cases and typically exhibits aggressive clinical behaviors. This study investigated the genetic aberration of 9p24.1 and protein expression of PD-L1 and also analyzed the clinicopathological association of these genetic lesions in CHL-IDD. Our findings showed that PD-L1 expression and 9p24.1 copy number alterations were observed in all patients analyzed in this study. Though it is recognized that an increase in 9p24.1 copy number alteration is associated with a more aggressive clinical course in immunocompetent CHL patients, we identified a subset of the 9p24.1 copy gain group, which had less 9p24.1 copy number alteration than the amplification group, exhibited more extensive extranodal lesions and had higher clinical stages in CHL-IDD cases. This finding speculates the presence of a genetically distinct subgroup within CHL-IDD patients, which may explain certain characteristic features. A subset of patients with rheumatoid arthritis receiving methotrexate develop immune deficiencies and dysregulation-associated lymphoproliferative disorders. Patients with these disorders often exhibit spontaneous regression after MTX withdrawal; however, chemotherapeutic intervention is frequently required in patients with classic Hodgkin lymphoma arising in immune deficiency/dysregulation. In this study, we examined PD-L1 expression levels and 9p24.1 copy number alterations in 27 patients with classic Hodgkin lymphoma arising from immune deficiency/dysregulation. All patients demonstrated PD-L1 protein expression and harbored 9p24.1 copy number alterations on the tumor cells. When comparing clinicopathological data and associations with 9p24.1 copy number features, the copy gain group showed a significantly higher incidence of extranodal lesions and clinical stages than the amplification group. Notably, all cases in the amplification group had latency type II, while 6/8 (75%) in the copy gain group had latency type II, and 2/8 (25%) had latency type I. Thus, a subset of the copy-gain group demonstrated more extensive extranodal lesions and higher clinical stages. This finding speculates the presence of a genetically distinct subgroup within the group of patients who develop immune deficiencies and dysregulation-associated lymphoproliferative disorders, which may explain certain characteristic features. [ABSTRACT FROM AUTHOR]

Simple Summary: The use of robot-assisted radical cystectomy (RARC) is increasing, although its definitive superiority over open radical cystectomy (ORC) has not been proven. Randomized controlled trials (RCTs) have demonstrated RARC's superiority regarding perioperative and functional outcomes but not in terms of oncologic and survival outcomes. Composite outcomes, such as the trifecta and pentafecta, have been proposed to evaluate the quality of the surgery. The aim of our retrospective study was to assess the superiority of RARC over ORC using the PROMETRIC group's trifecta and pentafecta criteria in a propensity score-matched analysis to reduce biases. No differences were found in the success rates of trifecta and pentafecta. The overall survival was comparable between the two cohorts. We confirmed the superiority of RARC in significantly reducing the estimated blood loss and perioperative transfusion rates. Background: This study aimed to evaluate the surgical and oncological outcomes of robot-assisted radical cystectomy (RARC) versus open radical cystectomy (ORC) using trifecta and pentafecta parameters. Methods: The clinical data of 41 patients who underwent RARC between 2018 and 2022 were prospectively collected and retrospectively compared to those of 330 patients undergoing ORC using 1:1 propensity score matching. Trifecta was defined as simultaneous negative surgical margins (SMs), a lymph node (LN) yield ≥ 16, and the absence of major complications (Clavien–Dindo grade III–V) within 90 days postoperatively. Pentafecta additionally included a 12-month recurrence-free rate and a time between the transurethral resection of a bladder tumor (TURBT) and radical cystectomy (RC) ≤ 3 months. The continuous variables were compared using the Mann–Whitney U test, and the categorical variables were analyzed using the chi-squared test. Results: No statistically significant differences in trifecta and pentafecta success rates were observed between the RARC and ORC cohorts after propensity score matching. However, the RARC group exhibited significantly reduced blood loss (RARC: 317 mL vs. ORC: 525 mL, p = 0.01). Conclusions: RARC offers distinct advantages over ORC in terms of reduced blood loss, while trifecta and pentafecta success rates do not differ significantly between the two surgical approaches. [ABSTRACT FROM AUTHOR]

Simple Summary: Bronchopleural fistula after lobectomy for lung cancer is a rare and life-threatening complication. Recognizing and managing this complication in time is often very complex for the clinicians and surgeons. Several surgical and endoscopic therapeutic approaches were described for the management of broncho-pleural fistula during the time period under study; however, the various instituted treatments depend much more on the experiences of individual centers than on a codified algorithm. Indeed, at present, there are no codified guidelines in the literature for its treatment. On the basis of our 25 years of experience, we tried to outline a diagnostic and therapeutic algorithm to help clinicians in the management of this feared complication Backgrounds: Our goal is to evaluate the correct management of broncho-pleural fistula (BPF) after lobectomy for lung cancer. Methods: We retrospectively reviewed our 25-years' experience and reported our strategies and our diagnostic algorithm for the management of post-lobectomy broncho-pleural fistula. Results: Five thousand one hundred and fifty (5150) patients underwent lobectomy for lung cancer in the period between 1998 and 2023. A total of 44 (0.85%) out of 5150 developed post-operative BPF. In 11 cases, BPF was solved by non-invasive treatment. In nine cases, direct surgical repair of the bronchial stump allowed BPF resolution. In 14 cases, a completion intervention was performed. In six cases, we performed open window thoracostomy (OWT) after lobectomy; in two cases, the BPF was closed by percutaneous injection of an n-butyl cyanoacrylate glue mixture. In two cases, no surgical procedure was performed because of the clinical status of the patient at the time of fistula developing. Thirty-day and ninety-day mortality from fistula onset was, respectively, 18.2% (eight patients) and 22.7% (ten patients). Thirty-day and ninety-day mortality after completion pneumonectomy (12 patients) was, respectively, 8.3% (one patient) and 16.6% (two patients). Conclusions: The correct management of BPF depends on various factors: timing of onset, size of the fistula, anatomic localization, and the general condition of the patient. In the case of failure of various initial therapeutic approaches, completion intervention or OWT could be considered. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aims to evaluate the feasibility of using changes in radiomic features over time (Delta radiomics) following chemotherapy to predict relapse/progression and time to progression (TTP) in primary mediastinal large B-cell lymphoma (PMBCL) patients. Analyzing data from 103 PMBCL patients, including end-of-treatment (EoT) scans and longitudinal radiomics features, the study employed various machine learning techniques for prediction. Results indicate that using Delta radiomics improves prediction accuracy for relapse/progression and TTP compared to using only EoT radiomics features. The study underscores the importance of EoT scans and the potential of Delta radiomics in predicting disease progression in PMBCL patients based on [18F]FDG PET-CT scans. Objectives: Accurate outcome prediction is important for making informed clinical decisions in cancer treatment. In this study, we assessed the feasibility of using changes in radiomic features over time (Delta radiomics: absolute and relative) following chemotherapy, to predict relapse/progression and time to progression (TTP) of primary mediastinal large B-cell lymphoma (PMBCL) patients. Material and Methods: Given the lack of standard staging PET scans until 2011, only 31 out of 103 PMBCL patients in our retrospective study had both pre-treatment and end-of-treatment (EoT) scans. Consequently, our radiomics analysis focused on these 31 patients who underwent [18F]FDG PET-CT scans before and after R-CHOP chemotherapy. Expert manual lesion segmentation was conducted on their scans for delta radiomics analysis, along with an additional 19 EoT scans, totaling 50 segmented scans for single time point analysis. Radiomics features (on PET and CT), along with maximum and mean standardized uptake values (SUVmax and SUVmean), total metabolic tumor volume (TMTV), tumor dissemination (Dmax), total lesion glycolysis (TLG), and the area under the curve of cumulative standardized uptake value-volume histogram (AUC-CSH) were calculated. We additionally applied longitudinal analysis using radial mean intensity (RIM) changes. For prediction of relapse/progression, we utilized the individual coefficient approximation for risk estimation (ICARE) and machine learning (ML) techniques (K-Nearest Neighbor (KNN), Linear Discriminant Analysis (LDA), and Random Forest (RF)) including sequential feature selection (SFS) following correlation analysis for feature selection. For TTP, ICARE and CoxNet approaches were utilized. In all models, we used nested cross-validation (CV) (with 10 outer folds and 5 repetitions, along with 5 inner folds and 20 repetitions) after balancing the dataset using Synthetic Minority Oversampling TEchnique (SMOTE). Results: To predict relapse/progression using Delta radiomics between the baseline (staging) and EoT scans, the best performances in terms of accuracy and F1 score (F1 score is the harmonic mean of precision and recall, where precision is the ratio of true positives to the sum of true positives and false positives, and recall is the ratio of true positives to the sum of true positives and false negatives) were achieved with ICARE (accuracy = 0.81 ± 0.15, F1 = 0.77 ± 0.18), RF (accuracy = 0.89 ± 0.04, F1 = 0.87 ± 0.04), and LDA (accuracy = 0.89 ± 0.03, F1 = 0.89 ± 0.03), that are higher compared to the predictive power achieved by using only EoT radiomics features. For the second category of our analysis, TTP prediction, the best performer was CoxNet (LASSO feature selection) with c-index = 0.67 ± 0.06 when using baseline + Delta features (inclusion of both baseline and Delta features). The TTP results via Delta radiomics were comparable to the use of radiomics features extracted from EoT scans for TTP analysis (c-index = 0.68 ± 0.09) using CoxNet (with SFS). The performance of Deauville Score (DS) for TTP was c-index = 0.66 ± 0.09 for n = 50 and 0.67 ± 03 for n = 31 cases when using EoT scans with no significant differences compared to the radiomics signature from either EoT scans or baseline + Delta features (p-value> 0.05). Conclusion: This work demonstrates the potential of Delta radiomics and the importance of using EoT scans to predict progression and TTP from PMBCL [18F]FDG PET-CT scans. [ABSTRACT FROM AUTHOR]

Simple Summary: The recent increase in oropharyngeal cancer cases in Western countries prompted this research, which focuses on evaluating the role of human papillomavirus (HPV) in the incidence of this cancer type in Romania. This study employed p16 overexpression as a biomarker to distinguish HPV-related oropharyngeal cancers from those attributed to other etiologies, like smoking and alcohol consumption. Comparative analysis of treatment responses revealed a markedly improved prognosis in patients with p16-positive oropharyngeal cancers, underscoring the significance of HPV in the pathogenesis and clinical outcomes of these malignancies. Background: Oropharyngeal cancer is a global health concern due to its multifaceted nature. Recent molecular studies have linked p16 overexpression, associated with the human papillomavirus, to oropharyngeal cancer and its prognostic implications. Materials and Methods: This retrospective study in Western Romania examined 60 patients, categorizing them based on p16 biomarker status: 28 were p16 positive, and 32 were p16 negative. Statistical tests, including Fisher's exact and chi2, were used for analysis. Results: Patients with p16-positive oropharyngeal cancer exhibited a better prognosis (3-year survival, p = 0.0477; midtreatment, p = 0.0349) and reported lower alcohol (p = 0.0046) and tobacco (p < 0.0001) use. Conclusions: The study highlights the importance of p16 testing in oropharyngeal carcinoma diagnosis. It suggests modifying treatment approaches based on p16 status and underscores the differing prognoses associated with p16-positive and p16-negative cases. [ABSTRACT FROM AUTHOR]

Simple Summary: Ablative radiotherapy for central early stage non-small cell lung cancer (NSCLC) is controversial in its feasibility and optimal dose prescription due to the risk of severe pneumonia and adverse events associated with mediastinal organs. Carbon-ion radiotherapy (CIRT) is a promising modality of radiotherapy with steep and linear dose distribution and high biological efficacy. We retrospectively analyzed the long-term results of ablative CIRT using 68.4 Gy in 12 fractions for central early stage NSCLC. Irradiation doses to lungs and mediastinal organs such as bronchus and esophagus were controlled and no serious mediastinal organ-related adverse events occurred. In addition, the efficacy was not inferior to that reported in previous studies, including photon SBRT or proton radiotherapy. This means that our CIRT regimen is expected to have a relatively high safety profile for central NSCLC with tumor and organ at risk (OAR) proximity. The aim of this study is to assess the efficacy and safety of ablative carbon ion radiotherapy (CIRT) for early stage central non-small cell lung cancer (NSCLC). We retrospectively reviewed 30 patients who had received CIRT at 68.4 Gy in 12 fractions for central NSCLC in 2006–2019. The median age was 75 years, and the median Karnofsky Performance Scale score was 90%. All patients had concomitant chronic obstructive pulmonary disease, and 20 patients (67%) were considered inoperable. In DVH analysis, the median lung V5 and V20 were 15.5% and 10.4%, and the median Dmax, D0.5cc, D2cc of proximal bronchial tree was 65.6 Gy, 52.8 Gy, and 10.0 Gy, respectively. At a median follow-up of 43 months, the 3-year overall survival, disease-specific survival, and local control rates were 72.4, 75.8, and 88.7%, respectively. Two patients experienced grade 3 pneumonitis, but no grade ≥3 adverse events involving the mediastinal organs occurred. Ablative CIRT is feasible and effective for central NSCLC and could be considered as a treatment option, especially for patients who are intolerant of other curative treatments. [ABSTRACT FROM AUTHOR]

Simple Summary: Targeted therapies have revolutionized the treatment of patients with non-small cell lung cancer (NSCLC). Adenocarcinoma, the most common histological subtype of NSCLC, is the posterchild of this therapeutic approach because of its high rate of treatable targets. In our study, we provide evidence that squamous cell carcinoma (SCC), the second most common histological subtype of NSCLC, also harbors a significant number of treatable targets, although at a lower rate than adenocarcinoma. Furthermore, we show that most SCC patients harboring such an alteration were >50 years of age and current or former smokers, questioning restrictive molecular testing strategies. Based on our data, we propose that broad molecular profiling should be performed in all newly diagnosed NSCLC cases, irrespective of histological subtype, but also irrespective of age or smoking status. Due to the success story of biomarker-driven targeted therapy, most NSCLC guidelines agree that molecular reflex testing should be performed in all cases with non-squamous cell carcinoma (non-SCC). In contrast, testing recommendations for squamous cell carcinoma (SCC) vary considerably, specifically concerning the exclusion of patients of certain age or smoking status from molecular testing strategies. We performed a retrospective single-center study examining the value of molecular reflex testing in an unselected cohort of 316 consecutive lung SCC cases, tested by DNA- and RNA-based next-generation sequencing (NGS) at our academic institution between 2019 and 2023. Clinicopathological data from these cases were obtained from electronic medical records and correlated with sequencing results. In 21/316 (6.6%) cases, we detected an already established molecular target for an approved drug. Among these were seven cases with an EGFR mutation, seven with a KRAS G12C mutation, four with an ALK fusion, two with an EGFR fusion and one with a METex14 skipping event. All patients harboring a targetable alteration were >50 years of age and most of them had >15 pack-years, questioning restrictive molecular testing strategies. Based on our real-world data, we propose a reflex testing workflow using DNA- and RNA-based NGS that includes all newly diagnosed NSCLC cases, irrespective of histology, but also irrespective of age or smoking status. [ABSTRACT FROM AUTHOR]

Simple Summary: There is limited literature on sample adequacy for molecular testing and genomic sequencing for pancreatic ductal adenocarcinoma obtained via EUS fine-needle aspiration (FNA) versus EUS fine-needle biopsy (FNB). Thus, we aimed to compare these two modalities regarding sample adequacy for molecular testing and genomic sequencing. In this retrospective chart review study, we analyzed all patients with pancreatic ductal adenocarcinoma who underwent EUS at Saint Luke's Hospital, Kansas City, MO, from 1 January 2018, to 31 December 2021. A rapid on-site evaluation was performed for all cases by cytotechnologists. We found that out of 1417 EUS procedures, 132 patients underwent EUS-guided biopsies. The mean number of passes required for FNB and FNA was similar. However, EUS-FNB, under rapid on-site specimen evaluation guidance, was superior to FNA in obtaining adequate samples for molecular testing. In addition, tumor surface area and tumor cellularity are essential parameters in determining sample adequacy for molecular testing, regardless of the tissue acquisition modality. Background and Aims: There is limited literature on sample adequacy for molecular testing in pancreatic ductal adenocarcinoma obtained via endoscopic ultrasound (EUS) fine-needle aspiration (FNA) versus EUS fine-needle biopsy (FNB). We aimed to compare these two modalities regarding sample adequacy for molecular and genomic sequencing. Methods: We reviewed all patients with pancreatic ductal adenocarcinoma who underwent EUS at Saint Luke's Hospital from 2018 to 2021. The patients were categorized based on the method of EUS tissue acquisition, specifically FNA or FNB. A comprehensive evaluation was conducted for all cases by cytotechnologists. Results: Out of 132 patients who underwent EUS-guided biopsies, 76 opted for FNA, 48 opted for FNB, and 8 opted for a combination of both. The average number of passes required for FNB and FNA was 2.58 ± 1.06 and 2.49 ± 1.07, respectively (p = 0.704), indicating no significant difference. Interestingly, 71.4% (35) of FNB-obtained samples were deemed adequate for molecular testing, surpassing the 32.1% (26) adequacy observed with FNA (p < 0.001). Additionally, 46.4% (26) of FNB-obtained samples were considered adequate for genomic testing, a notable improvement over the 23.8% (20) adequacy observed with FNA (p = 0.005). Conclusion: Although the number of passes required for cytologic diagnosis did not differ significantly between EUS-FNB and EUS-FNA, the former demonstrated superiority in obtaining samples adequate for molecular testing. Tumor surface area and cellularity were crucial parameters in determining sample adequacy for molecular testing, irrespective of the chosen tissue acquisition modality. [ABSTRACT FROM AUTHOR]

Simple Summary: This study was conducted to compare two endoscopic procedures for managing malignant gastric outlet obstruction. The first and most commonly used procedure is enteral stenting, which is safe, easy, and widely available. The second procedure, endoscopic ultrasound-guided gastroenterostomy (EUS-GE), is more challenging, can result in severe adverse events, and requires specific skills. However, EUS-GE, which bypasses the tumor, could have some advantages in terms of the stent dysfunction rate. Our study found that stent dysfunction occurred more frequently after enteral stenting, while stent patency was longer after EUS-GE. However, the early clinical efficacy was comparable between the two procedures and was influenced by patients' performance status. This study suggests that the choice between these two techniques should be personalized based on several factors, including patients' prognosis and life expectancy, clinical success, and local expertise. Background: Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) using lumen apposing metal stent has emerged as a minimally invasive treatment for the management of malignant gastric outlet obstruction (mGOO). We aimed to compare EUS-GE with enteral stenting (ES) for the treatment of mGOO. Methods: Patients who underwent EUS-GE or ES for mGOO between June 2017 and June 2023 at two Italian centers were retrospectively identified. The primary outcome was stent dysfunction. Secondary outcomes included technical success, clinical failure, safety, and hospital length of stay. A propensity score-matching analysis was performed using multiple covariates. Results: Overall, 198 patients were included (66 EUS-GE and 132 ES). The stent dysfunction rate was 3.1% and 16.9% following EUS-GE and ES, respectively (p = 0.004). Using propensity score-matching, 45 patients were allocated to each group. The technical success rate was 100% for both groups. Stent dysfunction was higher in the ES group compared with the EUS-GE group (20% versus 4.4%, respectively; p = 0.022) without differences in clinical efficacy (p = 0.266) and safety (p = 0.085). A significantly shorter hospital stay was associated with EUS-GE compared with ES (7.5 ± 4.9 days vs. 12.5 ± 13.0 days, respectively; p = 0.018). Kaplan–Meier analyses confirmed a higher stent dysfunction-free survival rate after EUS-GE compared with ES (log-rank test; p = 0.05). Conclusion: EUS-GE offers lower rates of stent dysfunction, longer stent patency, and shorter hospital stay compared with ES. [ABSTRACT FROM AUTHOR]

Simple Summary: Photodynamic therapy (PDT) has emerged as a versatile treatment option for head and neck disorders. The purpose of our review was to provide an overview of the use of PDT therapy in a variety of diseases. The use of PDT therapy has recently emerged as an innovative and effective method of cancer treatment. However, more and more studies are showing that it is also promising for treating a variety of non-cancerous lesions, providing a minimally invasive alternative for certain conditions. The same following principles apply: the application of a photosensitizer, exposure to light, and then the destruction of abnormal cells. In our work, we highlighted the importance of photodynamic therapy and its valuable treatment as an option for a variety of diseases of the head and neck area, not just cancer. With this, we want to encourage researchers to more widely use photodynamic therapy in head and neck disorders. Photodynamic therapy (PDT) has emerged as a promising modality for the treatment of various diseases. This non-invasive approach utilizes photosensitizing agents and light to selectively target and destroy abnormal cells, providing a valuable alternative to traditional treatments. Research studies have explored the application of PDT in different areas of the head. Research is focusing on a growing number of new developments and treatments for cancer. One of these methods is PDT. Photodynamic therapy is now a revolutionary, progressive method of cancer therapy. A very important feature of PDT is that cells cannot become immune to singlet oxygen. With this therapy, patients can avoid lengthy and costly surgeries. PDT therapy is referred to as a safe and highly selective therapy. These studies collectively highlight the potential of PDT as a valuable therapeutic option in treating the head area. As research in this field progresses, PDT may become increasingly integrated into the clinical management of these conditions, offering a balance between effectiveness and minimal invasiveness. [ABSTRACT FROM AUTHOR]

Simple Summary: Nevus-associated cutaneous melanoma (CM) is a malignant melanocytic proliferation occurring in the context of a pre-existing benign melanocytic nevus. This type of melanoma is not infrequent, accounting for up to 35% of all superficial spreading CMs. Discriminating between malignant and benign cellular populations may be challenging, but it is mandatory for diagnostic and staging purposes and is consequently critical for accurate patient management. The aim of this study was to assess the diagnostic performance of PRAME immunohistochemistry in this clinical setting. In this study, PRAME immunohistochemistry showed a perfect specificity and a good sensitivity, showing negative values for all nevus components and positive values for 59.4% of the malignant cellular components. The diagnostic agreement between morphology and PRAME immunohistochemistry was perfect for the diagnosis of nevus components and fair for the diagnosis of malignant components. PRAME was significantly more expressed in thick invasive CMs than in thin cases (p = 0.02). Our results support the use of PRAME immunohistochemistry as a useful tool in the diagnosis of nevus-associated CM. (1) Background: Nevus-associated cutaneous melanoma (CM) is relatively common in the clinical practice of dermatopathologists. The correct diagnosis and staging of nevus-associated cutaneous melanoma (CM) mainly relies on the correct discrimination between benign and malignant cells. Recently, PRAME has emerged as a promising immunohistochemical marker of malignant melanocytes. (2) Methods: PRAME immunohistochemistry (IHC) was performed in 69 cases of nevus-associated CMs. Its expression was evaluated using a score ranging from 0 to 4+ based on the percentage of melanocytic cells with a nuclear expression. PRAME IHC sensitivity, specificity, positive predictive values, and negative predictive values were assessed. Furthermore, the agreement between morphological data and PRAME expression was evaluated for the diagnosis of melanoma components and nevus components. (3) Results: PRAME IHC showed a sensitivity of 59%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 71%. The diagnostic agreement between morphology and PRAME IHC was fair (Cohen's Kappa: 0.3); the diagnostic agreement regarding the benign nevus components associated with CM was perfect (Cohen's Kappa: 1.0). PRAME was significantly more expressed in thick invasive CMs than in thin cases (p = 0.02). (4) Conclusions: PRAME IHC should be considered for the diagnostic evaluation of nevus-associated CM and is most useful in cases of thick melanomas. Pathologists should carefully consider that a PRAME-positive cellular population within the context of a nevus could indicate a CM associated with the nevus. A negative result does not rule out this possibility. [ABSTRACT FROM AUTHOR]

Simple Summary: Low molecular weight heparin (LMWH) has been the standard of care for venous thromboembolism (VTE) but new guidelines approved using non-vitamin K antagonist oral anticoagulants (NOAC). By conducting an individual patient data meta-analysis of randomised controlled trials (RCTs) comparing the outcomes of NOAC versus LMWH in cancer patients, we aim to determine an ideal strategy for the prophylaxis of VTE and prevention of VTE recurrence. Our study further addresses the conflicting evidence in the literature with an individual patient data meta-analysis. However, other studies are required to balance the risk of recurrent VTE and bleeding among different cancer subgroups. Emerging data highlight the need for individualised antithrombotic strategies to achieve optimal management of cancer patients. Venous thromboembolism (VTE) is a leading cause of morbidity and mortality in cancer patients. Low molecular weight heparin (LMWH) has been the standard of care but new guidelines have approved the use of non-vitamin K antagonist oral anticoagulants (NOAC). By conducting an individual patient data (IPD) meta-analysis of randomised controlled trials (RCTs) comparing the outcomes of NOAC versus LMWH in cancer patients, we aim to determine an ideal strategy for the prophylaxis of VTE and prevention of VTE recurrence. Three databases were searched from inception until 19 October 2022. IPD was reconstructed from Kaplan–Meier curves. Shared frailty, stratified Cox and Royston–Parmar models were fit to compare the outcomes of venous thromboembolism recurrence and major bleeding. For studies without Kaplan–Meier curves, aggregate data meta-analysis was conducted using random-effects models. Eleven RCTs involving 4844 patients were included. Aggregate data meta-analysis showed that administering NOACs led to a significantly lower risk of recurrent VTE (RR = 0.65; 95%CI: 0.50–0.84) and deep vein thrombosis (DVT) (RR = 0.60; 95%CI: 0.40–0.90). In the IPD meta-analysis, NOAC when compared with LMWH has an HR of 0.65 (95%CI: 0.49–0.86) for VTE recurrence. Stratified Cox and Royston–Parmar models demonstrated similar results. In reducing risks of recurrent VTE and DVT among cancer patients, NOACs are superior to LMWHs without increased major bleeding. [ABSTRACT FROM AUTHOR]

Simple Summary: On rare occasions, a handful of innovative cancer drugs may successfully go through clinical trials and manage to obtain simultaneous regulatory approvals to treat a specific disease, providing hope for improved treatment outcomes. In the past few years, physicians in North America, Europe, and other countries with stronger economies have been able to use several of the recently approved drugs to treat a blood cancer called multiple myeloma, once older therapies have failed. This study looked at the treatment outcomes associated with the wave of newer drugs in patients diagnosed with multiple myeloma in Greece. The results showed that approximately three-quarters of patients who received one of the newer drugs after having progressed on front-line therapies remained in remission a year after initiating treatment. This finding was comparable to the results from previous studies in Greek patients who were diagnosed with relapsed or refractory multiple myeloma and had previously used other therapies. Newer methodologies are needed to assess the real-world comparative effectiveness of a "generation" of pharmaceutical innovation versus the prior standard of care. This chart review study aimed to first evaluate the cumulative clinical benefits of pharmaceutical innovation in everyday relapse/refractory multiple myeloma before analyzing findings in the context of respective real-world outcomes from the bortezomib/lenalidomide era. Study endpoints included the 52-week PFS rate in second and third line of therapy (LOT), mPFS-2 across the first and second LOT, the ORR, reasons for discontinuation, and the treatment duration per therapeutic algorithm. Data from 107 patients were collected. The median follow-up was 2.0 years. Of the subjects who met the selection criteria for the second LOT, 72.2% maintained the PFS at 52 weeks. In the third-line setting, the PFS rate at 52 weeks was 63.5%. The mPFS across the first and second, the second, and the third LOTs were 26, 17, and 15 months, respectively. The ORR was 76.1% in the second and 69.7% in the third LOT. After non-response or progression, the main reason for drug discontinuation was treatment intolerability. The second-line ORR and the 52-week PFS rate were similar to previous real-world findings from the bortezomib/lenalidomide era. The cumulative mPFS across the second and third LOTs was higher than the respective mPFS across the first and second LOTs. Despite its limitations, the methodology and findings from this study may be used in future clinical and economic evaluations across all hematological malignancies. [ABSTRACT FROM AUTHOR]