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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 -
The Oncologist Jun 2024Immune checkpoint inhibitors (ICIs) have revolutionized cancer care with incredible reductions in mortality. One of the most devastating complications of treatment is...
BACKGROUND
Immune checkpoint inhibitors (ICIs) have revolutionized cancer care with incredible reductions in mortality. One of the most devastating complications of treatment is ICI-related pneumonitis (ICI-p). Despite this, little is known regarding risk factors for severe pneumonitis and treatment effectiveness of various therapeutic options for steroid-refractory disease. To address this, we conducted a retrospective study on patients with cancer who developed ICI-p.
METHODS
We examined consecutive patients who received ICIs and developed ICI-p. Risk factors of interest for severe disease and steroid-refractory ICI-p, including pre-treatment pulmonary function tests (PFTs) and chest imaging, were compared between patients with severe (grades 3-5) and mild (grades 1-2) pneumonitis. The clinical and treatment courses for patients with steroid-refractory ICI-p were recorded.
RESULTS
A total of 132 patients developed ICI-p, with 60 patients having mild and 72 with severe disease. We found that lower forced vital capacity percent predicted (66.24 vs 85.05, P = .05), lower total lung capacity percent predicted (85.23 vs 99.71, P = .13), and specific radiographic patterns on pre-treatment chest imaging were predictors of severe disease. Initial corticosteroid dose of less than 1 milligram per kilogram prednisone equivalent (P = .14) was correlated with partially steroid-responsive or steroid-refractory ICI-p. Ten patients had steroid refractory ICI-p, and those who received IVIG alone as the immune suppressant beyond corticosteroids had improved survival (P = 05).
CONCLUSIONS
We are the first to identify pre-treatment PFTs and chest imaging abnormalities as risk factors for severe ICI-p. We also found that lower corticosteroid doses were associated with partially steroid-responsive and steroid-refractory ICI-p. Larger, prospective studies are needed to validate our results.
PubMed: 38886156
DOI: 10.1093/oncolo/oyae147 -
The Oncologist Jun 2024Sarcopenia or skeletal muscle depletion is a poor prognostic factor for gastric cancer (GC). However, existing cutoff values of skeletal muscle index (SMI) for defining...
BACKGROUND
Sarcopenia or skeletal muscle depletion is a poor prognostic factor for gastric cancer (GC). However, existing cutoff values of skeletal muscle index (SMI) for defining sarcopenia have been found to have limitations when clinically applied. This study aimed to determine the optimal cutoff for SMI to predict severe toxicities of chemotherapy and overall survival (OS) in patients with advanced GC.
METHODS
Patients with metastatic gastric adenocarcinoma who received first-line palliative chemotherapy between January 2014 and December 2021 at Queen Mary Hospital, Hong Kong, were included in this study. The SMI was determined via a pre-chemotherapy computed tomography scan. Optimal cutoff points of SMI were identified by recursive partitioning analysis. Univariate and multivariate analyses evaluating risk factors of severe chemotherapy toxicities and OS were also performed.
RESULTS
A total of 158 patients (male: 108 (68.4%), median age: 65.3) were included. The SMI cutoff to define low SMI was ≤33 cm2/m2 for males and ≤28 cm2/m2 for females; 30 patients (19.0%) had low SMI. Patients with low SMI had a higher incidence of hematological toxicities (63.3% vs 32.0%, P = .001) and non-hematological toxicities (66.7% vs 36.7%, P = .003). Multivariable analysis indicated that low SMI and low serum albumin (≤28 g/L) were independent predictive factors of hematological toxicity, while low SMI and neutrophil-lymphocyte ratio ≥5 were predictive factors of non-hematological toxicity. Moreover, patients with low SMI had a significantly shorter OS (P = .011), lower response rate to chemotherapy (P = .045), and lower utilization of subsequent lines of treatment (P < .001).
CONCLUSIONS
Using pre-chemotherapy SMI cutoff (≤33 cm2/m2 for males and 28 cm2/m2 for females) one can identify individuals with a higher risk of severe chemotherapy toxicities and worse prognosis.
PubMed: 38885304
DOI: 10.1093/oncolo/oyae123 -
The Oncologist Jun 2024The activity of PARP inhibitors (PARPi) in patients with homologous recombination repair (HRR) mutations and metastatic castration-resistant prostate cancer has been...
TRIUMPH: phase II trial of rucaparib monotherapy in patients with metastatic hormone-sensitive prostate cancer harboring germline homologous recombination repair gene mutations.
BACKGROUND
The activity of PARP inhibitors (PARPi) in patients with homologous recombination repair (HRR) mutations and metastatic castration-resistant prostate cancer has been established. We hypothesized that the benefit of PARPi can be maintained in the absence of androgen deprivation therapy (ADT) in an HRR-mutated population. We report the results of a phase II clinical trial of rucaparib monotherapy in patients with metastatic hormone-sensitive prostate cancer (mHSPC).
METHODS
This was a multi-center, single-arm phase II trial (NCT03413995) for patients with asymptomatic, mHSPC. Patients were required to have a pathogenic germline mutation in an HRR gene for eligibility. All patients received rucaparib 600 mg by mouth twice daily, without androgen deprivation. The primary endpoint was a confirmed PSA50 response rate.
RESULTS
Twelve patients were enrolled, 7 with a BRCA1/2 mutation and 5 with a CHEK2 mutation. The confirmed PSA50 response rate to rucaparib was 41.7% (N = 5/12, 95% CI: 15.2-72.3%, one-sided P = .81 against the 50% null), which did not meet the pre-specified efficacy boundary to enroll additional patients. In patients with measurable disease, the objective response rate was 60% (N = 3/5), all with a BRCA2 mutation. The median radiographic progression-free survival on rucaparib was estimated at 12.0 months (95% CI: 8.0-NR months). The majority of adverse events were grade ≤2, and expected.
CONCLUSION
Rucaparib can induce clinical responses in a biomarker-selected metastatic prostate cancer population without concurrent ADT. However, the pre-specified efficacy threshold was not met, and enrolment was truncated. Although durable responses were observed in a subset of patients, further study of PARPi treatment without ADT in mHSPC is unlikely to change clinical practice.
PubMed: 38885246
DOI: 10.1093/oncolo/oyae120