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Diagnostics (Basel, Switzerland) May 2024Cancer-associated thrombosis is the second leading cause of death in cancer patients, and its incidence has been increasing in recent years. This survey was aimed at...
Cancer-associated thrombosis is the second leading cause of death in cancer patients, and its incidence has been increasing in recent years. This survey was aimed at gathering information regarding the management of thromboembolic prophylaxis within the MITO (Multicenter Italian Trials in Ovarian Cancer)-MaNGO (Mario Negri Gynecologic Oncology) groups. We designed a self-administered, multiple-choice online questionnaire available only for MITO-MaNGO members for one month, starting in May 2022 and ending in June 2022. We processed one response form per center, and 50 responses were analyzed, with most of the respondents (78%) over 40 years old. We found that 82% of them consider thromboembolic prophylaxis in gynecologic oncology to be relevant. In 82% of the centers, a standardized protocol on venous thromboembolism (VTE) prophylaxis is used, which is applied to both patients undergoing surgery and those undergoing chemotherapy. In the remaining 18% of centers, prophylaxis is used exclusively for patients undergoing chemotherapy treatment. Prophylaxis of patients undergoing surgery and chemotherapy treatment is managed in most cases by the surgeon (72%) and oncologist (76%), respectively. Only 26% of respondents use a thromboembolic risk assessment scale, and of these, those used are the Caprini Score (6%), Khorana Score (6%), and Wells Score (2%). The respondents have good knowledge of low-molecular-weight heparin (90%) and average knowledge of dicumarolics (40%), direct oral anticoagulants (DOACs) (68%), and antiplatelet agents (40%). The results of our survey indicate that there is a good awareness of thromboembolic prophylaxis in gynecologic oncology. Nevertheless, it is used less in outpatients than in patients undergoing surgery. Moreover, the thromboembolic risk assessment scores are barely used.
PubMed: 38893685
DOI: 10.3390/diagnostics14111159 -
Diagnostics (Basel, Switzerland) May 2024Determination of microsatellite instability (MSI)/mismatch repair (MMR) status in cancer has several clinical implications. Our aim was to integrate MSI/MMR status from...
Determination of microsatellite instability (MSI)/mismatch repair (MMR) status in cancer has several clinical implications. Our aim was to integrate MSI/MMR status from patients tested in Greece to assess the prevalence of MSI-high (MSI-H)/deficient MMR (dMMR) per tumor type, testing patterns over time and concordance between MSI and MMR status. We retrospectively recorded MSI/MMR testing data of patients with diverse tumor types performed in pathology and molecular diagnostics laboratories across Greece. Overall, 18 of 22 pathology and/or molecular diagnostics laboratories accepted our invitation to participate. In the 18 laboratories located across the country, 7916 tumor samples were evaluated for MSI/MMR status. MSI/MMR testing significantly increased in patients with colorectal cancer (CRC) and other tumor types overtime ( < 0.05). The highest prevalence was reported in endometrial cancer (47 of 225 patients, 20.9%). MSI-H/dMMR was observed in most tumor types, even in low proportions. Among 904 tumors assessed both for MSI and MMR status, 21 had discordant results (overall discordance rate, 2.3%). We reported MSI-H/dMMR prevalence rates in patients with diverse cancers, while demonstrating increasing referral patterns from medical oncologists in the country overtime. The anticipated high rate of concordance between MSI and MMR status in paired analysis was confirmed.
PubMed: 38893603
DOI: 10.3390/diagnostics14111076 -
Cancers May 2024Improved rates of cancer control have increased the head and neck cancer survivor population. Cancer survivorship clinics are not widely available in the USA, and...
Improved rates of cancer control have increased the head and neck cancer survivor population. Cancer survivorship clinics are not widely available in the USA, and longitudinal supportive care for patients undergoing multimodal therapy has not advanced at a pace commensurate with improvements in cancer control. Consequently, a large head and neck cancer survivor population whose quality of life may be chronically and/or permanently diminished presently exists. This lack of awareness perpetuates under-recognition and under-investigation, leaving survivors' (mostly detrimental) experiences largely uncharted. We conducted a qualitative exploration of survivors' experiences, aiming to unpack the profound impact of late systemic symptoms on daily life, encompassing work, relationships, and self-identity in the head and neck cancer survivor community. The study included 15 remitted head and neck survivors, ≥12 months from their final treatment, who participated in semi-structured interviews conducted by a medical oncologist. Data analysis comprised qualitative thematic analysis, specifically inductive hierarchical linear modeling, enriched by a deductive approach of anecdotal clinical reporting. Results highlighted that 43.36% of all quotation material discussed in the interviews pertained to chronic emotion disturbance with significant implications for other domains of life. A central symptom cluster comprised impairments in mood/emotions, daily activity, and significant fatigue. Dysfunction in sleep, other medical conditions, and cognitive deficits comprised a secondary cluster. Physical dysfunctionality, encompassing pain, appetite, and eating, and alterations in experienced body temperature, constituted a tertiary cluster, and perhaps were surprisingly the least discussed symptom burden among head and neck cancer survivors. Symptoms causing heightened long-term survivor burden may be considered epiphenomenal to central physical dysfunctionality, albeit being presently the least represented in cancer survivor care programs. Moving forward, the development of targeted and multi-dimensional treatment programs that encompass physical, psychosocial, and spiritual domains are needed to increase clinical specificity and effective holistic long-term solutions that will foster a more compassionate and informed future of care for the cancer survivorship community.
PubMed: 38893225
DOI: 10.3390/cancers16112106 -
Nutrients May 2024Multiple endocrine neoplasia type 1 (MEN1) is a rare syndrome caused by inactivating mutations in the MEN1 tumor suppressor gene. The three main clinical manifestations... (Review)
Review
Multiple endocrine neoplasia type 1 (MEN1) is a rare syndrome caused by inactivating mutations in the MEN1 tumor suppressor gene. The three main clinical manifestations of MEN1 are primary hyperparathyroidism (PHPT), duodenal-pancreatic neuroendocrine tumors (DP-NETs) and anterior pituitary tumors. Endocrine tumors in patients with MEN1 differ from sporadic tumors because of their younger age at onset, common multiple presentations and the different clinical course. MEN1 is characterized by a complex clinical phenotype; thus, patients should be followed by a multidisciplinary team of experts that includes an endocrinologist, a surgeon, a oncologist, a radiotherapist, and not least, a nutritionist. It is important to remember the fundamental role that diet plays as a primary prevention tool, together with a healthy and active lifestyle in preventing osteoporosis/osteopenia and reducing the risk of developing kidney stones due to hypercalciuria, two frequent clinical complications in MEN1 patients. Is very important for MEN1 patients to have an adequate intake of calcium, vitamin D, magnesium and phosphate to maintain good bone health. The intake of foods containing oxalates must also be kept under control because in combination with calcium they concur to form calcium oxalate crystals, increasing the risk of nephrolithiasis. Another aspect to consider is the management of patients with pancreatic neuroendocrine tumors undergoing major surgical resections of the pancreas that can lead to alterations in digestion and absorption mechanisms due to partial or total reduction in pancreatic enzymes such as amylase, lipase, and protease, resulting in malabsorption and malnutrition. Therefore, the nutritionist's aim should be to devise a dietary plan that takes into consideration each single patient, educating them about a healthy and active lifestyle, and accompanying them through various life stages by implementing strategies that can enhance their quality of life.
Topics: Humans; Multiple Endocrine Neoplasia Type 1; Nutritional Status
PubMed: 38892509
DOI: 10.3390/nu16111576 -
International Journal of Molecular... May 2024Multigene prognostic genomic assays have become indispensable in managing early breast cancer (EBC), offering crucial information for risk stratification and guiding... (Review)
Review
Multigene prognostic genomic assays have become indispensable in managing early breast cancer (EBC), offering crucial information for risk stratification and guiding adjuvant treatment strategies in conjunction with traditional clinicopathological parameters. The American Society of Clinical Oncology (ASCO) guidelines endorse these assays, though some clinical contexts still lack definitive recommendations. The dynamic landscape of EBC management demands further refinement and optimization of genomic assays to streamline their incorporation into clinical practice. The breast cancer community is poised at the brink of transformative advances in enhancing the clinical utility of genomic assays, aiming to significantly improve the precision and effectiveness of both diagnosis and treatment for women with EBC. This article methodically examines the testing methodologies, clinical validity and utility, costs, diagnostic frameworks, and methodologies of the established genomic tests, including the Oncotype Dx Breast Recurrence Score, MammaPrint, Prosigna, EndoPredict, and Breast Cancer Index (BCI). Among these tests, Prosigna and EndoPredict have at present been validated only on a prognostic level, while Oncotype Dx, MammaPrint, and BCI hold both a prognostic and predictive role. Oncologists and pathologists engaged in the management of EBC will find in this review a thorough comparison of available genomic assays, as well as strategies to optimize the utilization of the information derived from them.
Topics: Humans; Breast Neoplasms; Female; Prognosis; Genomics; Biomarkers, Tumor; Genetic Testing
PubMed: 38891906
DOI: 10.3390/ijms25115717 -
BMJ Open Jun 2024Oncologists need competence in clinical prognostication to deliver appropriate care to patients with cancer. Most studies on prognostication have been restricted to...
How accurate is clinical prognostication by oncologists during routine practice in a general hospital and can it be improved by a specific prognosis training programme: a prospective interventional study.
OBJECTIVES
Oncologists need competence in clinical prognostication to deliver appropriate care to patients with cancer. Most studies on prognostication have been restricted to patients in palliative care settings. This paper investigates (1) the prognostic accuracy of physicians regarding a broad cohort of patients with cancer with a median life expectancy of >2 years and (2) whether a prognosis training can improve prognostication.
DESIGN
Prospective single-centre study comprising 3 phases, each lasting 1 month.
SETTING
Large teaching hospital, department of oncology and haematology, Germany.
PARTICIPANTS
18 physicians with a professional experience from entry level to 34 years. 736 patients with oncological and malignant haematological diseases.
INTERVENTIONS
Baseline prognostication abilities were recorded during an 'untrained' phase 1. As an intervention, a specific prognosis-training programme was implemented prior to phases 2 and 3. In phase 3, physicians had to provide additional estimates with the inclusion of electronic prognostic tools.
OUTCOME MEASURES
Prognostic estimates (PE) were collected using 'standard' surprise question (SQ), 'probabilistic' SQ (both for short-term prognostication up to 6 months) and clinician prediction of survival (CPS) (for long-term prognostication). Estimated prognoses were compared with observed survival. Phase 1 was compared with phases 2 and 3.
RESULTS
We included 2427 PE for SQ, 1506 for CPS and 800 for probabilistic SQ. Median OS was 2.5 years. SQ accuracy improved significantly (p<0.001) from 72.6% in phase 1 to 84.3% in phase 3. Probabilistic SQ in phase 3 showed 83.1% accuracy. CPS accuracy was 25.9% and could not be significantly improved. (Electronic) prognostic tools-used alone-performed significantly worse (p<0.0005) than physicians and-used by the clinicians-did not improve their performance.
CONCLUSION
A specific prognosis-training programme could improve short-term and intermediate-term prognostication. Improvement of long-term prognostication was not possible. Inexperienced residents as well as experienced oncologists benefited from training.
Topics: Humans; Prospective Studies; Prognosis; Male; Female; Middle Aged; Clinical Competence; Neoplasms; Germany; Aged; Hospitals, General; Adult; Oncologists; Medical Oncology
PubMed: 38890134
DOI: 10.1136/bmjopen-2023-081661 -
JAMA Network Open Jun 2024Large language models (LLMs) recently developed an unprecedented ability to answer questions. Studies of LLMs from other fields may not generalize to medical oncology, a...
IMPORTANCE
Large language models (LLMs) recently developed an unprecedented ability to answer questions. Studies of LLMs from other fields may not generalize to medical oncology, a high-stakes clinical setting requiring rapid integration of new information.
OBJECTIVE
To evaluate the accuracy and safety of LLM answers on medical oncology examination questions.
DESIGN, SETTING, AND PARTICIPANTS
This cross-sectional study was conducted between May 28 and October 11, 2023. The American Society of Clinical Oncology (ASCO) Oncology Self-Assessment Series on ASCO Connection, the European Society of Medical Oncology (ESMO) Examination Trial questions, and an original set of board-style medical oncology multiple-choice questions were presented to 8 LLMs.
MAIN OUTCOMES AND MEASURES
The primary outcome was the percentage of correct answers. Medical oncologists evaluated the explanations provided by the best LLM for accuracy, classified the types of errors, and estimated the likelihood and extent of potential clinical harm.
RESULTS
Proprietary LLM 2 correctly answered 125 of 147 questions (85.0%; 95% CI, 78.2%-90.4%; P < .001 vs random answering). Proprietary LLM 2 outperformed an earlier version, proprietary LLM 1, which correctly answered 89 of 147 questions (60.5%; 95% CI, 52.2%-68.5%; P < .001), and the best open-source LLM, Mixtral-8x7B-v0.1, which correctly answered 87 of 147 questions (59.2%; 95% CI, 50.0%-66.4%; P < .001). The explanations provided by proprietary LLM 2 contained no or minor errors for 138 of 147 questions (93.9%; 95% CI, 88.7%-97.2%). Incorrect responses were most commonly associated with errors in information retrieval, particularly with recent publications, followed by erroneous reasoning and reading comprehension. If acted upon in clinical practice, 18 of 22 incorrect answers (81.8%; 95% CI, 59.7%-94.8%) would have a medium or high likelihood of moderate to severe harm.
CONCLUSIONS AND RELEVANCE
In this cross-sectional study of the performance of LLMs on medical oncology examination questions, the best LLM answered questions with remarkable performance, although errors raised safety concerns. These results demonstrated an opportunity to develop and evaluate LLMs to improve health care clinician experiences and patient care, considering the potential impact on capabilities and safety.
Topics: Humans; Cross-Sectional Studies; Medical Oncology; Educational Measurement; Language
PubMed: 38888919
DOI: 10.1001/jamanetworkopen.2024.17641 -
The Oncologist Jun 2024Colorectal cancer (CRC) is a common cancer in younger adults. In patients undergoing liver resection with RAS-altered CRCs, there is evidence suggesting younger patients...
Colorectal cancer (CRC) is a common cancer in younger adults. In patients undergoing liver resection with RAS-altered CRCs, there is evidence suggesting younger patients have worse outcomes than older patients. To explain this pattern, differences in associations between RAS status and other cancer-related biomarkers in tumors from younger versus older patients with CRC were evaluated in a cohort of 925 patients with CRC, 277 (30.0%) of whom were ≤50 years old, and 454 (49.1%) who had RAS-altered tumors. For 3 biomarkers, RNF43, APC, and microsatellite instability (MSI), the association with RAS status was significantly modified by age after adjustment for multiple testing. Specifically, younger patients with RAS-altered tumors were more likely to be MSI-high, RNF43 mutated, and APC wild type. These differences might contribute to the observed pattern of diminished survival in younger versus older patients with CRC with RAS-mutated tumors undergoing liver metastasis resection.
PubMed: 38886182
DOI: 10.1093/oncolo/oyae153 -
The Oncologist Jun 2024A patient with gastrointestinal stroma tumor (GIST) and KIT p.V559D and BRAF p.G469A alterations was referred to our institutional molecular tumor board (MTB) to discuss...
A patient with gastrointestinal stroma tumor (GIST) and KIT p.V559D and BRAF p.G469A alterations was referred to our institutional molecular tumor board (MTB) to discuss therapeutic implications. The patient had been diagnosed with B-cell chronic lymphocytic leukemia (CLL) years prior to the MTB presentation. GIST had been diagnosed 1 month earlier. After structured clinical annotation of the molecular alterations and interdisciplinary discussion, we considered BRAF/KIT co-mutation unlikely in a treatment-naïve GIST. Discordant variant allele frequencies furthermore suggested a second malignancy. NGS of a CLL sample revealed the identical class 2 BRAF alteration, thus supporting admixture of CLL cells in the paragastric mass, leading to the detection of 2 alterations. Following the MTB recommendation, the patient received imatinib and had a radiographic response. Structured annotation and interdisciplinary discussion in specialized tumor boards facilitate the clinical management of complex molecular findings. Coexisting malignancies and clonal hematopoiesis warrant consideration in case of complex and uncommon molecular findings.
PubMed: 38886160
DOI: 10.1093/oncolo/oyae137 -
The Oncologist Jun 2024Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare neoplasms with an increasing annual incidence and prevalence. Many are metastatic at presentation or...
BACKGROUND
Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare neoplasms with an increasing annual incidence and prevalence. Many are metastatic at presentation or recur following surgical resection and require systemic therapy, for which somatostatin analogs such as octreotide or lanreotide comprise typical first-line therapies. Nonetheless, treatment options remain limited. Epigenetic processes such as histone modifications have been implicated in malignant transformation and progression. In this study, we evaluated the anti-proliferative effects of a histone deacetylase (HDAC) inhibitor, entinostat, which was computationally predicted to show anti-cancer activity, as confirmed in in vitro and in vivo models of GEP-NETs.
METHODS
This was a phase II study to evaluate the efficacy and safety of entinostat in patients with relapsed or refractory abdominal NETs. The primary objective was to estimate the objective response rate to entinostat. Additionally, with each patient as his/her own control we estimated the rates of tumor growth prior to enrollment on study and while receiving entinostat. Patients received 5 mg entinostat weekly until disease progression or intolerable toxicity. The dose could be changed to 10 mg biweekly for patients who did not experience grade ≥ 2 treatment-related adverse events (AEs) in cycle 1, but was primarily administered at the starting 5 mg weekly dose.
RESULTS
The study enrolled only 5 patients due to early termination by the drug sponsor. The first patient that enrolled had advanced disease and died within days of enrollment before follow-up imaging due to a grade 5 AE unrelated to study treatment and was considered non-evaluable. Best RECIST response for the remaining 4 patients was stable disease (SD) with time on study of 154+, 243, 574, and 741 days. With each patient as his/her own control, rates of tumor growth on entinostat were markedly reduced with rates 20%, 33%, 54%, and 68% of the rates prior to enrollment on study. Toxicities possibly or definitely related to entinostat included grade 2/3 neutrophil count decrease [2/4 (50%)/ 2/4 (50%)], grade 3 hypophosphatemia [1/4, (25%)], grade 1/2 fatigue [1/4 (25%)/ 2/4 (50%)], and other self-limiting grade 1/2 AEs.
CONCLUSION
In the treatment of relapsed or refractory abdominal NETs, entinostat 5 mg weekly led to prolonged SD and reduced the rate of tumor growth by 32% to 80% with an acceptable safety profile (ClinicalTrials.gov Identifier: NCT03211988).
PubMed: 38886159
DOI: 10.1093/oncolo/oyae118