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The Oncologist Jun 2023T-cell receptor (TCR-T) therapies are based on the expression of an introduced TCR targeting a tumor associated antigen (TAA) which has been studied in several trials in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
T-cell receptor (TCR-T) therapies are based on the expression of an introduced TCR targeting a tumor associated antigen (TAA) which has been studied in several trials in cutaneous melanoma. We conducted a systematic review and meta-analysis aiming to assess the primary efficacy of TCR-based adoptive cell therapy in cutaneous melanoma.
METHODS
We searched through PubMed electronic database from its inception until May 21, 2022. Primary endpoints were pooled objective response rate (ORR) and disease control rate (DCR). We conducted logistic regression analyses to identify potential predictive factors for tumor response.
RESULTS
From 187 patients, 50 showed an objective response (pooled ORR 28%; 95% CI, 20%-37%) and a pooled DCR of 38% (95% CI, 27%-50%). Median PFS was 2, 9 months (95% CI, 1.4-3.1). A trend toward higher PFS was demonstrated for patients treated with cancer/testis antigens targeting TCR-T cells (HR 0.91 95% CI, 0.64-1.3, P = .61) among whom, patients treated with NYESO-1 targeting TCR-T showed a significantly higher PFS (HR 0.63 95% CI, 0.64-0.98, P = .03). In addition, the number of infused cells was associated with a significantly higher likelihood of tumor response (OR 6.61; 95% CI, 1.68-21.6; P = .007).
CONCLUSION
TCR-T therapy shows promising results in terms of antitumor activity and survival similar to those reported for TILs with a significantly higher benefit for cancer/testis antigens targeting cells. Since TCR-based therapy shows advantages of great potential over classic ACT strategies, further research in solid cancers is warranted (PROSPERO ID CRD42022328011).
Topics: Male; Humans; Melanoma; Skin Neoplasms; Immunotherapy, Adoptive; Receptors, Antigen, T-Cell; Melanoma, Cutaneous Malignant
PubMed: 37036865
DOI: 10.1093/oncolo/oyad078 -
Oral Oncology Oct 2018The aim of this study was to integrate the available data published on odontogenic carcinosarcoma into a comprehensive analysis of their features, treatment and...
The aim of this study was to integrate the available data published on odontogenic carcinosarcoma into a comprehensive analysis of their features, treatment and recurrence. An electronic search with no publication date or language restriction was undertaken in March 2018 in the following databases: Medline Ovid, PubMed, Web of Science, Scopus and LILACS. Eligibility criteria included publications having enough clinical, imaginological and histopathological information to confirm a definite diagnosis of the neoplasm. Data were evaluated descriptively and statistically using the MedCalc software. The Kaplan-Meier method was used for survival analysis. The systematic review detected nine articles from eight countries. Six cases with no age predilection occurred in male individuals complaining of painful swelling in the posterior mandible. Radiographically, the lesions were large, with expansive radiolucency and with ill-defined borders and seven cases were associated with preexisting odontogenic lesions. Radical surgery was the treatment of choice in the majority of cases. Recurrences (n = 6), metastasis (n = 4) and death (n = 4) were frequently observed in many cases. Odontogenic carcinosarcoma is a very aggressive neoplasm with a poor prognosis. This study provides knowledge that could help surgeons, oncologists, otorhinolaryngologists and oral maxillofacial pathologists with the diagnosis and management of these lesions.
Topics: Adult; Age Distribution; Aged; Carcinosarcoma; Child; Female; Humans; Kaplan-Meier Estimate; Male; Mandibular Neoplasms; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Odontogenic Tumors; Sex Distribution; Young Adult
PubMed: 30220320
DOI: 10.1016/j.oraloncology.2018.08.017 -
Psycho-oncology Sep 2016Antidepressants are commonly used for the pharmacological treatment of depression. We aimed to summarise the prevalence of antidepressant prescription to cancer... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Antidepressants are commonly used for the pharmacological treatment of depression. We aimed to summarise the prevalence of antidepressant prescription to cancer patients, and differences by study or patient characteristics.
METHODS
PubMed, Embase, Web of Science, Scopus and psychINFO were searched using keywords 'psychotropic', 'antidepressants', 'prescription' and 'cancer'. Prevalence of antidepressants, type, dose and follow-up of antidepressants and prescriber details were extracted.
RESULTS
Overall, 1537 articles between 1979 and February 2015 were found, 38 met the inclusion criteria and were reviewed according to PRISMA guidelines. The prevalence rate of prescribing antidepressants to cancer patients was 15.6% (95% CI = 13.3-18.3). Prescription was significantly less common in studies from Asia (7.4%; 95% CI = 4.3-12.5), more common in female (22.6%; 95% CI = 16.0-31.0) or breast cancer patients (22.6%; 95% CI = 16.0-30.9). Selective serotonin reuptake inhibitors were the most frequently prescribed antidepressants. General practitioners and psychiatrists, followed by oncologists, were identified as the major providers of antidepressant prescriptions to cancer patients. Few studies reported the exact dose, length of time drugs were prescribed for or follow-up regimens.
CONCLUSIONS
There is considerable variation in the prescribing patterns of antidepressants across the world, with few studies reporting robust data on exact dose or follow-up regimens. Prospective studies that monitor antidepressant prescribing, including details of reasons for prescribing and the healthcare providers involved, dose, change in dose or type of medication and follow-up are needed to ascertain whether patients are being treated optimally and if side effects or drug-drug interactions are identified and managed. Copyright © 2016 John Wiley & Sons, Ltd.
Topics: Adult; Antidepressive Agents; Depression; Depressive Disorder; Drug Prescriptions; Humans; Neoplasms; Practice Patterns, Physicians'; Prospective Studies; Selective Serotonin Reuptake Inhibitors
PubMed: 26775715
DOI: 10.1002/pon.4048 -
Current Opinion in Oncology May 2015The everyday use of targeted therapies, whose mechanisms of action differ from the conventional cytotoxic agents, also causes the emergence of new toxicities as... (Review)
Review
PURPOSE OF REVIEW
The everyday use of targeted therapies, whose mechanisms of action differ from the conventional cytotoxic agents, also causes the emergence of new toxicities as metabolic disorders about which little is known. We propose a systematic literature review of the incidence and physiopathology of targeted therapies-induced metabolic disorders and provide some management guidance.
RECENT FINDINGS
In recent decades, significant breakthroughs in molecular oncology and immunology have been made. The administration of targeted therapies and immunotherapy has been associated with metabolic toxicities such as endocrine disorders, dyslipidemia, induced diabetes, and electrolytic disorders. Current data show that metabolic disorders are becoming increasingly common, but rarely life threatening and often reversible with prompt therapeutic intervention.
SUMMARY
In the era of targeted therapies, medical oncologists should know the symptoms, carefully monitor patients for potential metabolic disorders, and manage these emerging side-effects with the help of endocrinologists and other medical specialists.
Topics: Antineoplastic Agents; Humans; Immunosuppressive Agents; Metabolic Diseases; Molecular Targeted Therapy; Neoplasms; Observational Studies as Topic; Practice Guidelines as Topic; Protein Kinase Inhibitors; Quality of Life
PubMed: 25730544
DOI: 10.1097/CCO.0000000000000176 -
Ophthalmology May 2024To develop guidelines for ocular surveillance and early intervention for individuals with von Hippel-Lindau (VHL) disease.
PURPOSE
To develop guidelines for ocular surveillance and early intervention for individuals with von Hippel-Lindau (VHL) disease.
DESIGN
Systematic review of the literature.
PARTICIPANTS
Expert panel of retina specialists and ocular oncologists.
METHODS
A consortium of experts on clinical management of all-organ aspects of VHL disease was convened. Working groups with expertise in organ-specific features of VHL disease were tasked with development of evidence-based guidelines for each organ system. The ophthalmology subcommittee formulated questions for consideration and performed a systematic literature review. Evidence was graded for topic quality and relevance and the strength of each recommendation, and guideline recommendations were developed.
RESULTS
The quality of evidence was limited, and no controlled clinical trial data were available. Consensus guidelines included: (1) individuals with known or suspected VHL disease should undergo periodic ocular screening (evidence type, III; evidence strength, C; degree of consensus, 2A); (2) patients at risk of VHL disease, including first-degree relatives of patients with known VHL disease, or any patient with single or multifocal retinal hemangioblastomas (RHs), should undergo genetic testing for pathologic VHL disease gene variants as part of an appropriate medical evaluation (III/C/2A); (3) ocular screening should begin within 12 months after birth and continue throughout life (III/C/2A); (4) ocular screening should occur approximately every 6 to 12 months until 30 years of age and then at least yearly thereafter (III/C-D/2A); (5) ocular screening should be performed before a planned pregnancy and every 6 to 12 months during pregnancy (IV/D/2A); (6) ultra-widefield color fundus photography may be helpful in certain circumstances to monitor RHs, and ultra-widefield fluorescein angiography may be helpful in certain circumstances to detect small RHs (IV/D/2A); (7) patients should be managed, whenever possible, by those with subspecialty training, with experience with VHL disease or RHs, or with both and ideally within the context of a multidisciplinary center capable of providing multiorgan surveillance and access to genetic testing (IV/D/2A); (8) extramacular or extrapapillary RHs should be treated promptly (III/C/2A).
CONCLUSIONS
Based on available evidence from observational studies, broad agreement was reached for a strategy of lifelong surveillance and early treatment for ocular VHL disease. These guidelines were endorsed by the VHL Alliance and the International Society of Ocular Oncology and were approved by the American Academy of Ophthalmology Board of Trustees.
FINANCIAL DISCLOSURE(S)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Topics: Humans; Fluorescein Angiography; Genetic Testing; Hemangioblastoma; Retina; Retinal Neoplasms; von Hippel-Lindau Disease; Von Hippel-Lindau Tumor Suppressor Protein
PubMed: 38092079
DOI: 10.1016/j.ophtha.2023.12.014 -
Systematic Review of PD-1/PD-L1 Inhibitors in Oncology: From Personalized Medicine to Public Health.The Oncologist Oct 2021To review and summarize all U.S. Food and Drug Administration (FDA) approvals of programmed death (PD)-1 and PD-ligand 1 blocking antibodies (collectively referred to as... (Review)
Review
BACKGROUND
To review and summarize all U.S. Food and Drug Administration (FDA) approvals of programmed death (PD)-1 and PD-ligand 1 blocking antibodies (collectively referred to as PD-[L]1 inhibitors) over a 6-year period and corresponding companion/complementary diagnostic assays.
MATERIALS AND METHODS
To determine the indications and pivotal trials eligible for inclusion, approval letters and package inserts available on Drugs@FDA were evaluated for approved PD-[L]1 inhibitors to identify all new indications granted from the first approval of a PD-[L]1 inhibitor on September 4, 2014, through September 3, 2020. The corresponding FDA drug and device reviews from the marketing applications for the approved indications were identified through FDA internal records. Two reviewers independently extracted information for the endpoints, efficacy data, basis for approval, type of regulatory approval, and corresponding in vitro diagnostic device test. The results were organized by organ system and tumor type.
RESULTS
Of 70 Biologic Licensing Application or supplement approvals that resulted in new indications, 32 (46%) were granted based on response rate (ORR) and durability of response, 26 (37%) on overall survival, 9 (13%) on progression-free survival, 2 (3%) on recurrence-free survival, and 1 (1%) on complete response rate. Most ORR-based approvals were granted under the accelerated approval provisions and were supported with prolonged duration of response. Overall, 21% of approvals were granted with a companion diagnostic. Efficacy results according to tumor type are discussed.
CONCLUSION
PD-[L]1 inhibitors are an effective anticancer therapy in a subset of patients. This class of drugs has provided new treatment options for patients with unmet need across a wide variety of cancer types. Yet, the modest response rates in several tumor types signal a lack of understanding of the biology of these diseases. Further preclinical and clinical investigation may be required to identify a more appropriate patient population, particularly as drug development continues and additional treatment alternatives become available.
IMPLICATIONS FOR PRACTICE
The number of PD-[L]1 inhibitors in drug development and the associated companion and complementary diagnostics have led to regulatory challenges and questions regarding generalizability of trial results. The interchangeability of PD-L1 immunohistochemical assays between PD-1/PD-L1 drugs is unclear. Furthermore, robust responses in some patients with low levels of PD-L1 expression have limited the use of PD-L1 as a predictive biomarker across all cancers, particularly in the setting of diseases with few alternative treatment options. This review summarizes the biomarker thresholds and assays approved as complementary and companion diagnostics and provides regulatory perspective on the role of biomarkers in oncology drug development.
Topics: B7-H1 Antigen; Humans; Immune Checkpoint Inhibitors; Neoplasms; Precision Medicine; Programmed Cell Death 1 Receptor; Public Health
PubMed: 34196068
DOI: 10.1002/onco.13887 -
The Oncologist Apr 2017The objective of this study was to review the role of bilateral salpingo-oophorectomy in mutation (m) carriers and alternative interventions in risk reduction of... (Review)
Review
OBJECTIVE
The objective of this study was to review the role of bilateral salpingo-oophorectomy in mutation (m) carriers and alternative interventions in risk reduction of ovarian cancer (OC).
MATERIALS AND METHODS
A systematic review using PubMed, MEDLINE, EMBASE, and the Cochrane library was conducted to identify studies of different strategies to prevent OC in m carriers, including bilateral salpingo-oophorectomy, prophylactic salpingectomy with delayed oophorectomy, intensive surveillance, and chemoprevention.
RESULTS
Risk-reducing bilateral salpingo-oophorectomy is an effective intervention, but its associated morbidity is substantial and seems to curtail uptake rates among the target population. Although there is much interest and a strong theoretical basis for salpingectomy with delayed oophorectomy, data on its clinical application are scarce with regard to screening, the use of an algorithmic protocol has recently shown favorable albeit indefinite results in average-risk postmenopausal women. Its incorporation into studies focused on high-risk women might help solidify a future role for screening as a bridge to surgery. The use of oral contraceptives for chemoprevention is well supported by epidemiologic studies. However, there is a lack of evidence for advocating any of the other agents proposed for this purpose, including nonsteroidal anti-inflammatory drugs, vitamin D, and retinoids.
CONCLUSION
Further studies are needed before salpingectomy with delayed oophorectomy or intensive surveillance can be offered as acceptable, less morbid alternatives to upfront oophorectomy for m carriers. 2017;22:450-459 IMPLICATIONS FOR PRACTICE: Risk-reducing bilateral salpingo-oophorectomy is currently the most effective method for reducing the risk of ovarian cancer in mutation (m) carriers. Unfortunately, it is associated with significant short- and long-term morbidity, stemming from reduced circulating estrogen. In recent years, much research has been devoted to evaluating less morbid alternatives, especially multimodal cancer screening and prophylactic salpingectomy with delayed oophorectomy. This review describes the present state of the art, with the aim of informing the counseling provided to m carriers on this complicated issue and encouraging additional research to facilitate the incorporation of such alternatives into routine practice.
Topics: BRCA1 Protein; BRCA2 Protein; Female; Heterozygote; Humans; Mutation; Ovarian Neoplasms; Risk Factors; Salpingo-oophorectomy
PubMed: 28314837
DOI: 10.1634/theoncologist.2016-0444 -
Reports of Practical Oncology and... 2020To assess the educational needs, role and perceptions in palliative care issues of radiation oncologists (ROs) and trainees. (Review)
Review
AIM
To assess the educational needs, role and perceptions in palliative care issues of radiation oncologists (ROs) and trainees.
BACKGROUND
1/3 of radiotherapy patients are treated with palliative intent. Conversely, education and role that ROs have in the palliative care process are not well established, neither in terms of how they perceive their competence nor whether it is important to improve training, research and attention in palliative care issues at radiotherapy congresses.
MATERIAL AND METHODS
Literature systematic review in National Library of Medicine and Cochrane databases with 11 relevant issues to be identified. One doctor made first selection of articles, a second one confirmed their eligibility.
RESULTS
722 articles reviewed, 19 selected. 100% recognize the importance of palliative care in radiotherapy, 89.4% the need of training in palliative care for ROs, 68.4% the necessity of improving the resident programs, 63.1% the importance of skilled ROs in palliative care, 63.1% the need of better communication skills and pain management (47.3%), 52.6%, the perception of inadequate training in palliative care, 36.8% the lack of research and palliative care topics in radiotherapy meetings, 21% the absence of adequate guidelines regarding palliative care approaches, 42.1% the importance of the ROs in palliative care teams and 26.3% the lack of their involvement.
CONCLUSION
Palliative care has an important role in radiotherapy but it seems ROs still need more training. It is necessary to improve training programs, increment palliative care research in radiotherapy, giving more attention to palliative care themes at radiotherapy congresses. This could lead to a better integration of radiotherapists in multidisciplinary palliative care teams in the future.
PubMed: 33093812
DOI: 10.1016/j.rpor.2020.09.007 -
Journal of Cancer Survivorship :... Feb 2023A cornerstone of treatment for many cancers is the administration of platinum-based chemotherapies and/or ionizing radiation, which can be ototoxic. An accurate... (Review)
Review
PURPOSE
A cornerstone of treatment for many cancers is the administration of platinum-based chemotherapies and/or ionizing radiation, which can be ototoxic. An accurate ototoxicity risk assessment would be useful for counseling, treatment planning, and survivorship follow-up in patients with cancer.
METHODS
This systematic review evaluated the literature on predictive models for estimating a patient's risk for chemotherapy-related auditory injury to accelerate development of computational approaches for the clinical management of ototoxicity in cancer patients. Of the 1195 articles identified in a PubMed search from 2010 forward, 15 studies met inclusion for the review.
CONCLUSIONS
All but 1 study used an abstraction of the audiogram as a modeled outcome; however, specific outcome measures varied. Consistently used predictors were age, baseline hearing, cumulative cisplatin dose, and radiation dose to the cochlea. Just 5 studies were judged to have an overall low risk of bias. Future studies should attempt to minimize bias by following statistical best practices including not selecting multivariate predictors based on univariate analysis, validation in independent cohorts, and clearly reporting the management of missing and censored data. Future modeling efforts should adopt a transdisciplinary approach to define a unified set of clinical, treatment, and/or genetic risk factors. Creating a flexible model that uses a common set of predictors to forecast the full post-treatment audiogram may accelerate work in this area. Such a model could be adapted for use in counseling, treatment planning, and follow-up by audiologists and oncologists and could be incorporated into ototoxicity genetic association studies as well as clinical trials investigating otoprotective agents.
IMPLICATIONS FOR CANCER SURVIVORS
Improvements in the ability to model post-treatment hearing loss can help to improve patient quality of life following cancer care. The improvements advocated for in this review should allow for the acceleration of advancements in modeling the auditory impact of these treatments to support treatment planning and patient counseling during and after care.
Topics: Child; Humans; Adult; Antineoplastic Agents; Prognosis; Ototoxicity; Quality of Life; Cancer Survivors; Neoplasms
PubMed: 36729346
DOI: 10.1007/s11764-022-01315-8 -
Cancers Mar 2023Childhood cancer patients and their families are increasingly offered oncofertility care including information regarding their risk of gonadal damage by paediatric... (Review)
Review
Experiences of Female Childhood Cancer Patients and Survivors Regarding Information and Counselling on Gonadotoxicity Risk and Fertility Preservation at Diagnosis: A Systematic Review.
BACKGROUND
Childhood cancer patients and their families are increasingly offered oncofertility care including information regarding their risk of gonadal damage by paediatric oncologists, fertility counselling by fertility specialists and fertility preservation options. However, experiences regarding oncofertility care are underreported. We aimed to summarize the available evidence of experiences of female childhood cancer patients and survivors regarding oncofertility care.
METHODS
Manuscripts were systematically identified using the PubMed and Embase database. From, respectively, 1256 and 3857 manuscripts, 7 articles were included and assessed, including risk of bias assessment. Outcome measures included data describing experiences of female childhood cancer patients and survivors, regarding fertility information, counselling and/or preservation.
RESULTS
Female patients and survivors are variably satisfied with fertility information, report challenges in communication with healthcare professionals and prefer to receive general information at diagnosis and detailed fertility information later. Regrets after fertility counselling are underreported, but are associated with refusing fertility preservation. Lastly, regardless of counselling, female patients and survivors report fertility concerns about their future children's health and effect on relationships.
CONCLUSION
Currently, the satisfaction with oncofertility care varies and female patients or survivors report regrets and concerns regardless of receiving fertility information or counselling. These results may help to improve the content of fertility information, communication skills of healthcare professionals and timing of counselling.
PubMed: 37046607
DOI: 10.3390/cancers15071946