Seminars In Oncology[JOURNAL]
Sun
200 papers
Chemotherapy plus immunotherapy as first line combination in older patients with extensive stage small cell lung cancer: A systematic review and meta-analysis.
Bertaglia V, Petrelli F, Dottorini L … +7 more , Carnio S, Morelli AM, Nepote A, Maccioni A, Scartozzi M, Solinas C, Novello S
Semin Oncol · 2025 Feb · PMID 39743384 · Publisher ↗
BACKGROUND: Small-cell lung cancer (SCLC) accounts for 10%-15% of all lung cancers. At diagnosis, nearly two thirds of patients with SCLC have extensive stage (ES), with a median overall survival (OS) less than 12 months...
BACKGROUND: Small-cell lung cancer (SCLC) accounts for 10%-15% of all lung cancers. At diagnosis, nearly two thirds of patients with SCLC have extensive stage (ES), with a median overall survival (OS) less than 12 months. The combination of protein-death-1/protein-death-ligand-1 (PD-1/PD-L1) immune checkpoint inhibitors (ICIs) with first-line platinum plus etoposide chemotherapy has changed the therapeutic landscape for ES-SCLC. Older adults represent most of the cancers diagnosed and deaths by age group, with an expected increase over the next decade. In the real-world setting, about 30%-40% of patients with a diagnosis of SCLC are reported to be over 70-years-old at the time of diagnosis. However, this subgroup of patients is underrepresented in clinical trials. Based on this evidence, we performed this systematic review to define the activity of ICIs plus chemotherapy in older patients with previously untreated ES-SCLC. METHODS: This systematic review was carried out in accordance with the statement in the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A systematic search on multiple electronic databases was conducted from inception to the end of April to identify randomized trials that prospectively evaluated chemotherapy ± PD-1/PD-L1 ICIs. When more than one report of the same study was available, the most recent data (with longer follow-up and/or higher number of patients) was considered. The primary endpoint of the study was efficacy, in terms of overall survival, progression-free survival, and disease control rate. RESULTS: We selected six randomized clinical trials that enrolled 3396 patients in the meta-analysis. In the experimental arm, 670 patients were 65 years of age and older compared to 504 in the control arm. In the subgroup of patients ≥65 years, adding ICIs to chemotherapy led to a significant benefit in OS [hazard ratio (HR) 0.80, 95% confidence interval (CI) 0.72-0.90). There was moderate but not-significant heterogenity among the trials (I = 47%, P = 0.07). CONCLUSION: This systematic review found that the combination of chemotherapy plus ICIs improved OS among older patients with ES-SCLC. Biomarker and comprehensive geriatric assessment are needed to improve the identification and selection of patients with cancer that are uniformly defined as older.
Gender-based differences in the efficacy of anti-EGFR/BRAF/MEK targeted therapy in patients with BRAF-mutated metastatic colorectal cancer.
Pala L, De Pas T, Cocorocchio E … +6 more , Catania C, Ceresoli G, Laszlo D, Zattarin E, Rossi G, Conforti F
Semin Oncol · 2025 Feb · PMID 39627078 · Publisher ↗
OBJECTIVES: We previously showed that men with melanoma harboring BRAF mutations had significantly lower benefit from targeted therapy as compared with women Here we explored the hypothesis that such gender-based dimorph...
OBJECTIVES: We previously showed that men with melanoma harboring BRAF mutations had significantly lower benefit from targeted therapy as compared with women Here we explored the hypothesis that such gender-based dimorphism in the efficacy of BRAF-pathway blockade extends to other tumor histotypes carrying pathogenic BRAF-mutations. METHODS: We retrospectively analyzed data from a cohort of patients with advanced colorectal-cancer (CRC) harboring BRAF V600E mutations, treated with anti-EGFR/BRAF/MEK targeted therapy. The primary objective was to assess the association between gender and outcome of patients treated with targeted therapy, in terms of overall response rate (ORR), progression-free survival (PFS) and overall survival (OS).A multivariable Cox proportional hazard regression model was used to assess the association between gender and PFS and OS, adjusted for other relevant clinical, pathological and molecular prognostic factors, including ECOG PS (0 vs 1-2), primary tumor site (right-side vs left-side), microsatellite instability status (instable [MSI] vs stable [MSS]), number of metastatic sites at treatment start, treatment type (double targeted therapy [ie, anti-EGFR + anti-BRAF] vs triple targeted therapy [ie, anti-EGFR + anti-BRAF + anti-MEK]) and mutational status of the RNF43 gene (wild type vs mutated). RESULTS: Ninety-eight patients with advanced CRC were included in the analysis: 59 (60%) were women and 39 (40%) men. The ORR was 43.1% in women vs only 23.7% in men (p-value = .05). Multivariable analysis adjusted for relevant clinical, pathological, and molecular variables associated with patients' prognosis, showed a significantly shorter PFS and OS in men as compared with women: the adjusted-HR was, respectively, 1.65 (95%CI,1.00-2.69; p = .04) for PFS and 1.83 (95%CI,1.08-3.08; p-value = .02) for OS. CONCLUSIONS: We confirmed a significant gender-based dimorphism in the efficacy of anti-EGFR/BRAF/MEK therapy in patients with advanced-CRC harboring BRAF mutations that warrant further investigation.
Role of neoadjuvant pembrolizumab in advanced melanoma.
Amir M, Khan ZA, Asad A … +1 more , Shaikh TG
Semin Oncol · 2024 · PMID 39551678 · Publisher ↗
Melanoma, a malignancy originating from melanocytes, poses a significant global health challenge, with approximately 325,000 cases and 57,000 deaths annually. Advanced melanoma (AM), categorized as stage III and IV, pres...
Melanoma, a malignancy originating from melanocytes, poses a significant global health challenge, with approximately 325,000 cases and 57,000 deaths annually. Advanced melanoma (AM), categorized as stage III and IV, presents considerable treatment challenges due to its complex mutational landscape. Traditional treatment options have included checkpoint inhibitors and BRAF inhibitors, with pembrolizumab emerging as a promising agent. Approved by the FDA and EMA for various stages of melanoma, pembrolizumab is a humanized monoclonal antibody that blocks the PD-1/PD-L1 interaction, thereby enhancing immune system-mediated tumor eradication. This abstract discusses a recent phase 2 clinical trial evaluating the efficacy of neoadjuvant (presurgery) versus adjuvant (postsurgery) pembrolizumab treatment in resectable stage III or IV melanoma. The study, involving 313 patients across 90 US hospitals, found that neoadjuvant-adjuvant pembrolizumab significantly improved event-free survival (72%) compared to adjuvant-only treatment (49%) after 2 years. Treatment-related adverse events were consistent with known profiles, including fatigue, nausea, and diarrhea, without new severe adverse effects. No increase in surgery-related complications was observed with neoadjuvant treatment. These findings suggest that neoadjuvant pembrolizumab offers substantial benefits over adjuvant-only treatment, although further research is warranted. Future studies should focus on larger cohorts, diverse demographics, and extended follow-up to validate these results and potentially integrate neoadjuvant pembrolizumab into standard treatment protocols for advanced melanoma.
Efficacy of metformin drug in preventing metabolic syndrome associated with androgen deprivation therapy (ADT) in prostate cancer patients: A systematic review and meta-analysis.
Yakout IA, Gallab MM, Mohamed DA … +5 more , Hamdar H, I Ibrahim S, Mohamed A, Abdelshafi A, Abd-ElGawad M
Semin Oncol · 2024 · PMID 39547874 · Publisher ↗
BACKGROUND: Prostate cancer patients undergoing long-term (Androgen deprivation therapy) ADT will tend to have metabolic changes. Metabolic syndrome represents the accumulation of several medical conditions that signific...
BACKGROUND: Prostate cancer patients undergoing long-term (Androgen deprivation therapy) ADT will tend to have metabolic changes. Metabolic syndrome represents the accumulation of several medical conditions that significantly increase the risk of developing severe diseases like cardiovascular disorders, insulin resistance, and hyperglycemia. We are conducting this systematic review and meta-analysis to fill up the gap and to resolve the debate regarding the effectiveness of metformin in reducing metabolic syndrome associated with ADT in prostate cancer patients. METHODS: We conducted the systematic review and meta-analysis according to the Handbook of Cochrane Systematic Review of Intervention and the PRISMA guidelines. We conducted the search process using the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Scopus, and Web of Science. We selected the articles that fit within the following criteria, Randomized Controlled Trials (RCTs) and Cohort studies which evaluate the efficacy of metformin in reducing metabolic syndromes for prostate cancer patients undergoing androgen deprivation therapy (ADT). The efficacy of metformin in metabolic syndrome that resulted from using androgen deprivation therapy for prostate cancer patients was evaluated by the changes from baseline in Body Mass Index (BMI), waist circumference by cm, glycated hemoglobin (HbA1c), and blood pressure both systolic and diastolic. Revman software Version 5.4.1 was used to perform all statistical analyses. RESULTS: Our search retrieved 781 records. Seven records were included in our study: 5 published randomized control clinical trials and 2 cohort studies and only 6 studies were included in the meta-analysis. For BMI the pooled effect estimates of 3 studies favored Metformin over placebo, but this is not a significant difference (MD = -0.9, P = 0.05), for systolic pressure the pooled effect estimates of 3 studies favored Metformin over placebo, but this is not a significantly different placebo (MD = -3.18, P = 0.22), for HBA1c the pooled effect estimates of 3 studies showed that no significant difference between placebo and metformin (MD = -0.01, P = 0.86)002E CONCLUSION: Despite the promising direction in some parameters, our findings underscore the need for further research to establish a clearer understanding of metformin's role in mitigating metabolic changes in prostate cancer patients undergoing ADT.
Screening Adherence for Second Primary Malignancies in Breast Cancer Survivors: Behaviors, Facilitators, and Barriers to Enhance Quality Care.
Mesa-Chavez F, Salazar-Alejo M, Villarreal-Garza C
Semin Oncol · 2024 · PMID 39542813 · Publisher ↗
Due to genetic, hormonal, and environmental factors, alongside increased life expectancy, breast cancer (BC) survivors have an increased risk of developing a second primary malignancy. Therefore, regular screening for ot...
Due to genetic, hormonal, and environmental factors, alongside increased life expectancy, breast cancer (BC) survivors have an increased risk of developing a second primary malignancy. Therefore, regular screening for other types of cancer is of utmost importance for their comprehensive care. This cross-sectional study evaluated BC survivors' compliance with cervical, lung, and colorectal cancer screening, and identified facilitators and barriers influencing adherence. Fifty-two BC survivors answered the study's survey. A total of three (6%) cases of second primary malignancies were self-reported. Cervical cancer screening was performed within the past 3 years among 37/50 (74%) eligible participants. Only 7/24 (29%) eligible participants underwent colorectal cancer screening within the last 10 years, including six colonoscopies and 1 occult blood test. No participant had an indication for lung cancer screening. The primary reason for noncompliance with both cervical and colorectal cancer screening was lack of physician's recommendation, accounting for 79% and 88% of cases, respectively. Nearly all participants (98%) affirmed that BC survivors should undergo screening for other types of cancer. Most (96%) stated that, if recommended by a physician, they would agree to undergo screening for other neoplasms. Even though most BC survivors acknowledged its importance, screening particularly for colorectal cancer exhibited suboptimal rates. Oncologists could play a crucial role in increasing cancer screening uptake by reminding patients of their corresponding recommendations to detect other types of cancer.
Adenocarcinoma on retrorectal cystic hamartoma: An illustrative image for a very rare diagnosis.
Pascual JFR, Alonso EA, Pérez LP … +1 more , Rico MÁ
Semin Oncol · 2024 · PMID 39542812 · Publisher ↗
Retrorectal cystic hamartoma (also known as tailgut cyst) is a congenital lesion that originates from debris from the embryonic caudal intestine. Incidentally diagnosed in more than half of cases, the treatment of choice...
Retrorectal cystic hamartoma (also known as tailgut cyst) is a congenital lesion that originates from debris from the embryonic caudal intestine. Incidentally diagnosed in more than half of cases, the treatment of choice is surgical resection. It is a very rare pathology whose oncological transformation constitutes a true pathological rarity.
Deciphering the US Regulatory Framework: Comparison Between Oncology Biosimilars and Reference Biologics.
Tandulje A, Varpe P, Chaugule P … +2 more , Raghuvanshi RS, Srivastava S
Semin Oncol · 2024 · PMID 39537476 · Publisher ↗
Biological oncology agents are vital in cancer care, but their exorbitant expenses present obstacles for patients, families, healthcare professionals, and insurance providers. The advent of biosimilars represents a trans...
Biological oncology agents are vital in cancer care, but their exorbitant expenses present obstacles for patients, families, healthcare professionals, and insurance providers. The advent of biosimilars represents a transformative solution, offering more affordable alternatives after the expiration of biologics patents. Biosimilar agents, similar to biological agents in structure, function, safety, and immunogenicity, enhance healthcare accessibility, improve outcomes, and reduce costs. Thus, the safety of biosimilars in clinical settings is of utmost importance. This review provides a detailed overview of the United States (US) regulatory framework for biosimilars along with a comparative analysis of Food and Drug Administration (FDA) approved biosimilar products. The FDA's "Biosimilar product information" database and "FDA's Purple Book" database were used to retrieve data on approved biosimilars and reference biologicals respectively. The study compares biosimilars and their reference products, examining their physiological action, pharmacokinetics, indications, adverse reactions, and immunogenicity test results and concludes that biosimilars do not have significant variations from their reference biologic products. This analysis will offer critical insights for medical practitioners, clinicians, and patients. It empowers stakeholders to make informed decisions, assessing whether biosimilars offer an equivalent level of safety compared to their reference products. Biosimilars are endorsed as credible substitutes for originator biologics, improving accessibility and affordability in cancer care, and benefiting patients and healthcare systems.
Integrated profile of tumor stage and mutational burden predicts disparate clinical responses to immune checkpoint inhibitors: A risk-benefit study.
Zheng M
Semin Oncol · 2024 · PMID 39537475 · Publisher ↗
Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, having demonstrated efficacy and leading to regulatory approvals of ICIs in cancers characterized by high tumor mutation burden (TMB). However, th...
Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, having demonstrated efficacy and leading to regulatory approvals of ICIs in cancers characterized by high tumor mutation burden (TMB). However, there remains a gap in determining their applicability and risk-benefit profile, across the broad spectrum of patients whose tumors harbor varying TMB levels across distinct tumor stages. By interrogating a large contemporary cohort comprised of 10,233 patients with a diagnosis of cancer across all tumor stages and TMB levels, this study revealed significantly improved overall survival (OS) following ICI therapy (P < .0001) in patients with a combination of ≥10 mut/Mb and stage IV disease. In contrast, ICI therapy is associated with markedly worse OS in patients with low TMB levels <10 mut/Mb and stages I, II, and III cancer. These findings highlight the critical interplay between TMB, tumor stage, and ICI treatment outcomes, underscoring the importance of integrating clinical and genetic characteristics in weighing the risk-benefit balance of ICI therapy. Although maximizing therapeutic benefits is crucial, it is equally important to identify and manage potential risks that may not be immediately apparent. This may require enrolling patients with less-severe or early-stage disease to enable long-term follow-up with effective clinical surveillance. By comprehensively evaluating the added benefit of improved treatment efficacy and the potential risk of adverse treatment outcome, a risk-benefit profile can optimize immunotherapy regimens, with profound implications for clinical decision-making and regulatory approvals of ICI.
Hepatitis B Virus Reactivation in Cancer Patients Receiving Chemotherapy-A Systematic Review and Meta-Analysis.
Deepan N, Maung ST, Decharatanachart P … +1 more , Chaiteerakij R
Semin Oncol · 2024 · PMID 39537474 · Publisher ↗
Hepatitis B virus (HBV) reactivation is a critical concern for patients with a diagnosis of cancer receiving chemotherapy worldwide. Our aim was to assess the rate of HBV reactivation during chemotherapy globally. We sys...
Hepatitis B virus (HBV) reactivation is a critical concern for patients with a diagnosis of cancer receiving chemotherapy worldwide. Our aim was to assess the rate of HBV reactivation during chemotherapy globally. We systematically reviewed PubMed, Embase, Scopus, and Google Scholar databases for chemotherapy-related HBV reactivation studies from inception until July 2023. A random-effects model was used to estimate the pooled reactivation rate. Total 86 studies involving 21,297 patients were included, comprising 62 and 24 studies from Eastern and Western regions. Pooled results indicated a 9% reactivation rate (95%CI: 7%-13%, I = 95%). Reactivation rates were 10% (95%CI: 7%-14%, I = 92%) for hematological malignancies and 5% (95%CI: 3%-9%, I = 94%) for solid tumors. Presence of HBV DNA, HBeAg, and HBsAg were correlated with reactivation rates of 29% (95%CI: 10%-60%, I = 91%), 23% (95%CI: 14%-36%, I = 78%), and 15% (95%CI: 11%-20%, I = 90%), respectively. For patients with positive anti-HBe Ab, anti-HBc, and anti-HBs Ab serology, pooled reactivation rates were 7% (95%CI: 3%-14%, I = 81%), 4% (95%CI: 3%-7%, I = 85%), and 3% (95%CI: 2%-6%, I = 80%), respectively. With antiviral prophylaxis, reactivation rates were 1% (95%CI: 0%-17%, I = 59%), 1% (95%CI: 0%-5%, I = 0%), 4% (95%CI: 2%-9%, I = 85%), and 6% (95%CI: 3%-12%, I = 32%) for patients receiving tenofovir, entecavir, lamivudine, and telbivudine, respectively. Patients with a diagnosis of cancer undergoing chemotherapy face increased risk of HBV reactivation. This analysis raises public awareness and serves as a resource for future clinical trials.
Colorectal cancer in Ethiopia: Epidemiological trends, diagnostic and laboratory capacities, and challenges.
Dagnaw GG, Dejene H
Semin Oncol · 2025 Feb · PMID 39537473 · Publisher ↗
Colorectal cancer (CRC) refers to cancer that develops in the colon or rectum, parts of the large intestine. It ranks as the third most prevalent form of cancer globally. Colorectal cancer is responsible for the morbidit...
Colorectal cancer (CRC) refers to cancer that develops in the colon or rectum, parts of the large intestine. It ranks as the third most prevalent form of cancer globally. Colorectal cancer is responsible for the morbidity of millions and the loss of hundreds of thousands of lives worldwide although the incidence varies significantly depending on geographical location. In recent years, CRC has decreased in high-income countries due to technological advancements in diagnosis and treatment. However, there is an increased occurrence of CRC morbidity and mortality in low- and middle-income countries. Colorectal cancer is becoming an emerging public health concern in Ethiopia. We noticed that the incidence rates have been lower compared to more developed countries, but recent years have seen a noticeable increase. This rise is attributed to factors such as changes in diet, lifestyle, and an aging population. Common risk factors include dietary shifts towards processed foods and red meat, physical inactivity, obesity, smoking, and alcohol consumption. Unfortunately, in Ethiopia, screening programs for CRC are not widespread, and limited access to diagnostic facilities, lack of public awareness, and insufficient healthcare infrastructure contribute to late-stage diagnoses or left without diagnosis. Treatment options, including surgery, chemotherapy, and radiotherapy, are available but not uniformly accessible across the country, posing challenges for timely and effective treatment. Addressing colorectal cancer in Ethiopia requires a comprehensive approach to enhance public awareness, improve screening and early detection, expand treatment facilities, and train healthcare professionals to provide effective care.
Deep Myometrial Infiltration leads to a measurable Inflammatory Response in Endometrial Cancer. A Prospective Observational Study.
Ronsini C, Iavarone I, Braca E … +7 more , Vastarella MG, Della Corte L, Vitale C, Andreoli G, La Mantia E, Cobellis L, de Franciscis P
Semin Oncol · 2024 · PMID 39537472 · Publisher ↗
BACKGROUNDS: This study aims to evaluate the correlation between inflammation indices, such as neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), platelet-lymphocyte ratio (PLR) and deep myometrial infil...
BACKGROUNDS: This study aims to evaluate the correlation between inflammation indices, such as neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), platelet-lymphocyte ratio (PLR) and deep myometrial infiltration (≥50%) prospectively in patients with endometrial carcinoma, providing insights into the interaction between these parameters MATERIAL AND METHODS: A prospective observational cohort study was conducted at AOU Vanvitelli in Naples, Italy, from August 2023 to March 2024. Data from 161 patients undergoing surgery for endometrial cancer, including preoperative blood counts and histopathological information, were collected. Statistical analyses were performed using R software. RESULTS: After logistic regression, NLR and MLR showed a statistically significant association with deep myometrial infiltration (NLR log(OR) 0.15, P = .040; MLR log(OR) 0.30, P = .008). However, after multivariate logistic regression which included other risk factors such as grading, histotype, and MSI only NLR retained statistical significance, (Log(Or) 0.18, P = .031). CONCLUSION: Our results demonstrate noticeable changes in inflammation indices associated with deep myometrial infiltration in endometrial carcinoma. Moreover, a correlation between NLR and deep myometrial infiltration exists regardless of microsatellite instability, histotype, and grading.
Assessment of PSA responses and changes in the rate of tumor growth (g-rate) with immune checkpoint inhibitors in US Veterans with prostate cancer.
Leuva H, Moran G, Jamaleddine N … +8 more , Meseha M, Zhou M, Im Y, Rosenberg TM, Park YA, Luhrs C, Bates SE, Faiena I
Semin Oncol · 2024 · PMID 38937152 · Publisher ↗
We examined data from US Veterans with prostate cancer (PC) to assess disease response to immune checkpoint inhibitors (ICI) as monotherapy or combined with abiraterone or enzalutamide to assess ICI efficacy in the real-...
We examined data from US Veterans with prostate cancer (PC) to assess disease response to immune checkpoint inhibitors (ICI) as monotherapy or combined with abiraterone or enzalutamide to assess ICI efficacy in the real-world. We queried the VA corporate data warehouse (CDW) to identify Veterans with a diagnosis of PC who received ICI for any malignancy and had ≥1 PSA measurement while receiving ICI. To evaluate ICI monotherapy, we restricted analysis to Veterans who had not received LHRH agonists/antagonists, PC-directed medical therapy, or radiation/extirpative surgery of the bladder/prostate within and preceding the duration of ICI administration. For ICI combination analysis, we identified Veterans who received abiraterone or enzalutamide for PC while on ICI. We calculated rates of tumor (PSA) growth (g-rates), comparing them to a 1:2 matched reference cohort. We identified 787 Veterans with PC and ≥1 PSA measurement while receiving an ICI. Median duration of ICI therapy was 155 days. 223 Veterans received ICI monotherapy, with only 17(8%) having a reduction in PSA (median decline = 43%). 12 (5%) had PSA declines >30% (PSA30) which included 6 (3%) who had PSA reductions greater than 50% (PSA50). Median g-rates for ICI plus abiraterone (n = 20) or enzalutamide (n = 31) were 0.000689/d and 0.002819/d, respectively, and were statistically insignificant compared to g-rates of matched cohorts receiving abiraterone (g = 0.000925/d, P = 0.73) or enzalutamide (g = 0.001929/d, P = 0.58) alone. Our data align with clinical trial data in PC, demonstrating limited benefit from ICI monotherapy and predicting no survival benefit from simultaneous abiraterone or enzalutamide with an ICI using g-rate.
Invasive lobular breast cancer: Focus on prevention, genetics, diagnosis, and treatment.
Corso G, Fusco N, Guerini-Rocco E … +31 more , Leonardi MC, Criscitiello C, Zagami P, Nicolò E, Mazzarol G, La Vecchia C, Pesapane F, Zanzottera C, Tarantino P, Petitto S, Bianchi B, Massari G, Boato A, Sibilio A, Polizzi A, Curigliano G, De Scalzi AM, Lauria F, Bonanni B, Marabelli M, Rotili A, Nicosia L, Albini A, Calvello M, Mukhtar RA, Robson ME, Sacchini V, Rennert G, Galimberti V, Veronesi P, Magnoni F
Semin Oncol · 2024 · PMID 38897820 · Publisher ↗
Invasive lobular cancer (ILC) is the most common of the breast cancer special types, accounting for up to 15% of all breast malignancies. The distinctive biological features of ILC include the loss of the cell adhesion m...
Invasive lobular cancer (ILC) is the most common of the breast cancer special types, accounting for up to 15% of all breast malignancies. The distinctive biological features of ILC include the loss of the cell adhesion molecule E-cadherin, which drives the tumor's peculiar discohesive growth pattern, with cells arranged in single file and dispersed throughout the stroma. Typically, such tumors originate in the lobules, are more commonly bilateral compared to invasive ductal cancer (IDC) and require a more accurate diagnostic examination through imaging. They are luminal in molecular subtype, and exhibit estrogen and progesterone receptor positivity and HER2 negativity, thus presenting a more unpredictable response to neoadjuvant therapies. There has been a significant increase in research focused on this distinctive breast cancer subtype, including studies on its pathology, its clinical and surgical management, and the high-resolution definition of its genomic profile, as well as the development of new therapeutic perspectives. This review will summarize the heterogeneous pattern of this unique disease, focusing on challenges in its comprehensive clinical management and on future insights and research objectives.
Isolated lung metastases from pancreatic ductal adenocarcinoma (PDAC): Diagnostic and therapeutic challenges of a different disease.
Giulia O, Alessandro B, Angelo C … +8 more , Paolo M, Rosa C, Marina M, Umberto P, Catia C, Giulia V, Massimo F, Michele R
Semin Oncol · 2024 · PMID 38879350 · Publisher ↗
Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis, mostly due to the high rate of distant dissemination. However, growing evidence shows that isolated lung recurrence or metastases (ILM) from PDAC are not on...
Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis, mostly due to the high rate of distant dissemination. However, growing evidence shows that isolated lung recurrence or metastases (ILM) from PDAC are not only less common, but also correlated with a better prognosis. Lung-only recurrence after surgery occurs later in time and is associated with more favorable prognostic characteristics of the primary tumor. Moreover, recent findings suggest that this specific site of metastases is characterized by an immunologically "hot" microenvironment and a more favorable molecular profile that could possibly justify its clinical behavior. Thus, ILM from PDAC emerge as a distinct entity, that might also benefit from a different therapeutic approach, possibly with the integration of surgery and de-intensified chemotherapy regimens, especially in selected patients. In this review we delve into the current scientific evidence on the clinical and biological characteristics of isolated LM from PDAC, also focusing on concerns with their diagnostic process and the therapeutic options for the management of this subset of patients.
Real-world experience with CDK4-6 inhibition in the old and oldest old with a diagnosis of breast cancer.
Sobrini-Morillo P, Ravot C, Herlédan C … +3 more , Sánchez-Castellano C, Cruz-Jentoft AJ, Falandry C
Semin Oncol · 2024 · PMID 38604898 · Publisher ↗
This study describes characteristics, toxicity and survival in old patients with HR+/HER2-breast cancer (BC) treated with CDK4/6 inhibitors. Retrospective observational study that included patients ≥ 75 years with HR+/HE...
This study describes characteristics, toxicity and survival in old patients with HR+/HER2-breast cancer (BC) treated with CDK4/6 inhibitors. Retrospective observational study that included patients ≥ 75 years with HR+/HER2-BC treated with CDK4/6 inhibitors between 2017 and 2021. Patients' general and cancer-related data were collected. Comprehensive Geriatric Assessment scales were gathered. Adverse events reported before each cycle were included. At the end of the follow-up period, mortality was retrospectively registered from medical records. All 19 patients (94.7% women, median age 77.9 ± 10.1) were at risk of frailty (G8 ≤ 14) and malnutrition (MNA-SF ≤ 11). Most were independent (52.7% Lawton ≥ 6), had no cognitive impairment (89.5%, MMSE ≥ 24), poor physical performance (70%, SPPB < 8; 62.5% TUG ≥ 12'') and polypharmacy (72.2%). Almost half had stage IV disease (47.1%). Palbociclib+letrozole was the most frequently prescribed treatment (36.8%). All patients developed some toxicity (94.7% hematologic, 36.8% renal) but except one, grade ≤ 2. Over the 42-month follow-up period, 10 reported progression and 8 died. The median survival time was 19.9 ± 3.4 months. Five months after starting treatment, the probability of survival was 73%. At 30 months, 53% of patients survived. We found a high risk of frailty and drug toxicity in this small sample. Most patients presented hematologic toxicity but to a low degree. The probability of survival increases with treatment.
RENO Study: Clinical characteristics, treatment patterns and survival results in patients with metastatic renal cell carcinoma in Northern Spain.
Badiola LB, Milagro NL, Lavín DC … +14 more , Peraita SL, Ibarbia MA, Kareaga MM, Fernández Del Rivero TP, Otero DSP, López VA, Fernández CÁ, Emborujo AL, Arnaiz IG, Rodríguez RF, Verdún-Aguilar J, Sagastibeltza N, Duran I, GONORTE Collaborative Group
Semin Oncol · 2024 · PMID 38604897 · Publisher ↗
BACKGROUND: The current available evidence on the management of metastatic renal cell cancer (mRCC) in real life is scarce in our environment. We present a summary of the existing real-world data and the results of an an...
BACKGROUND: The current available evidence on the management of metastatic renal cell cancer (mRCC) in real life is scarce in our environment. We present a summary of the existing real-world data and the results of an analysis describing the clinical characteristics, treatments, and health outcomes of patients with mRCC in northern Spain. METHODS: Retrospective observational study. Adult patients diagnosed with mRCC between Jan 2007 and Dec 2019 were included. Epidemiological, efficacy and toxicity data were collected. Median overall survival (OS) and progression-free survival (PFS) were determined using the Kaplan-Meier method. RESULTS: A total of 829 patients were included (median age at diagnosis:63 years;73% men). Median follow-up was 180 months. The preponderant histology was clear cell (85%). In 50% the initial diagnosis was advanced disease. The distribution according to IMDC prognosis was good (24%), intermediate (50%) and poor (26%). The most frequent metastatic locations were lung (68.3%) and lymph node (41.0%). Most patients (95%) received a first line (1L) systemic treatment, 60% were treated with a second line (2L) of therapy and 37% received third line (3L). A VEGFR-TKIs was the most common treatment (1L: 90%, n = 507; 2L: 49%, n = 233; 3L: 54%, n = 156) followed by mTOR inhibitors (1L: 2%, n = 4; 2L: 27%, n = 126; 3L: 23%, n = 68) and immunotherapy (1L: 3.7%, n = 25; 2L: 27%, n = 126). Median OS was 24.5 months in the general population. According to IMDC prognostic groups, OS was 52.5, 25.7 and 9 months respectively. From the start of the 1L, 2L, and 3L treatment, median PFS was: 1L: 7.8 (6.8-9.0); 2L: 4.9 (4.3-5.5); 3L: 4.3 (3.8-4.8) months. No unexpected toxicity was reported. CONCLUSIONS: The Real-World Data on the management of mRCC in Northern Spain are comparable in epidemiology, efficacy, and safety to studies conducted in other areas of the world. The significant reduction in the number of patients receiving second and subsequent lines of therapy hampers the access to new therapies developed in this context.
CAR T-cell therapy: A collaboration between authorized treatment centers and community oncologists.
Bishop MR, Kay GE
Semin Oncol · 2024 · PMID 38531760 · Publisher ↗
With the approval of the first CAR T-cell products for hematological malignancies in 2017, these autologous cell therapies have changed the treatment paradigm for patients with relapsed or refractory (r/r) non-Hodgkin ly...
With the approval of the first CAR T-cell products for hematological malignancies in 2017, these autologous cell therapies have changed the treatment paradigm for patients with relapsed or refractory (r/r) non-Hodgkin lymphoma (NHL), who have a poor prognosis and few effective treatment options. Despite the demonstrated clinical benefit in patients with r/r diffuse large B-cell lymphoma, mantle cell lymphoma, and follicular lymphoma, many patients who are eligible for CAR T-cell therapies do not receive them or are treated with CAR T cells as a later line of therapy at advanced stages of disease. Several barriers exist for referring patients to an authorized treatment center (ATC) for CAR T-cell therapy. Although most patients with NHL are treated by community-based oncologists, educational gaps may exist for some community oncologists about the availability of CAR T-cell therapies in certain indications, the overall treatment process, and how they can access these therapies for their patients. In addition to navigation of the referral process from the community setting to the ATC, other barriers include timely identification of candidates eligible for CAR T-cell therapy and logistical and reimbursement concerns. Here, we examine the patient CAR T-cell experience, which begins and ends in the community setting, and identify and discuss opportunities for improved collaboration between community oncologists and ATC physicians to help address barriers to treatment and enhance patient outcomes. Treatment decisions for a patient's second or third line of therapy for NHL are critically important, owing to declining probabilities for favorable outcomes with each successive line of therapy. For patients who are eligible, CAR T-cell therapies should be considered as early as possible in their treatment course. A better understanding of the CAR T-cell process, the patient's experience, and the collaboration necessary for timely patient identification, better access, and successful outcomes will enable more patients to benefit from CAR T-cell therapies.
Seminars in oncology 50th anniversary.
Fojo T
Semin Oncol · 2024 · PMID 38480106 · Publisher ↗
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PARP inhibitors in ovarian cancer.
Goldlust IS, Guidice E, Lee JM
Semin Oncol · 2024 · PMID 38262776 · Full text
Poly-ADP-ribose polymerase inhibitors (PARPis) were first approved for the treatment of epithelial ovarian cancer (EOC), where as a maintenance therapy they transformed clinical management of this disease in both patient...
Poly-ADP-ribose polymerase inhibitors (PARPis) were first approved for the treatment of epithelial ovarian cancer (EOC), where as a maintenance therapy they transformed clinical management of this disease in both patients with and without homologous recombination deficiency. In this review, we provide a historical overview of PARPi use in EOC and discuss recent updates on overall survival data, highlighting their impact on regulatory approvals. We explore their potential as combination regimens with antiangiogenic and cell-cycle checkpoint inhibitors, as well as other small molecule inhibitors, to overcome resistance mechanisms and enhance therapeutic efficacy, providing a future perspective on the use of PARPis in EOC treatment.
CDK4/6 inhibitors in the treatment of metastatic breast cancer: Focus on toxicity and safety.
Wekking D, Lambertini M, Dessì M … +5 more , Denaro N, Bardanzellu F, Garrone O, Scartozzi M, Solinas C
Semin Oncol · 2023 Dec · PMID 38245458 · Publisher ↗
The development of oral cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors, including palbociclib, ribociclib, and abemaciclib, has revolutionized the treatment landscape for patients with hormone-receptor-positive (HR...
The development of oral cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors, including palbociclib, ribociclib, and abemaciclib, has revolutionized the treatment landscape for patients with hormone-receptor-positive (HR+) and human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (BC). When combined with an aromatase inhibitor or fulvestrant, these agents have been approved as first-line therapy in the metastatic setting. Abemaciclib has also gained FDA approval for patients with HR-positive, HER2-negative, node-positive, early BC at high risk of recurrence. Moreover, ribociclib has recently improved disease-free survival in patients with stage II or III HR+/HER2-negative early BC. CDK4/6 inhibitors have favorable safety profiles. However, the available agents have different toxicity profiles that must be clearly discussed with the patients for optimal clinical decisions. This manuscript aims to review CDK4/6 inhibitor-related treatment-associated adverse events, identify risk factors for intolerable adverse events, and assess their safety in special patient populations such as the elderly and those with renal insufficiency. Enhanced knowledge and understanding of CDK4/6 inhibitor-related toxicities can improve treatment strategies and ultimately enhance patient care.
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