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Journal of Clinical Medicine Jun 2024Estrogen receptor (ER)-positive breast cancer (BC) is the most common BC subtype. Endocrine therapy (ET) targeting ER signaling still remains the mainstay treatment... (Review)
Review
Estrogen receptor (ER)-positive breast cancer (BC) is the most common BC subtype. Endocrine therapy (ET) targeting ER signaling still remains the mainstay treatment option for hormone receptor (HR)-positive BC either in the early or in advanced setting, including different strategies, such as the suppression of estrogen production or directly blocking the ER pathway through SERMs-selective estrogen receptor modulators-or SERDs-selective estrogen receptor degraders. Nevertheless, the development of de novo or acquired endocrine resistance still remains challenging for oncologists. The use of novel ET combined with targeted drugs, such as cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, has significantly improved long-term outcome rates, thus changing the therapeutic algorithm for metastatic BC (MBC) and recently the therapeutic strategy in the adjuvant setting for early high-risk BC. Eluding the resistance to CDK4/6 inhibitors combined with ET is currently an unmet medical need, and there is disagreement concerning the best course of action for patients who continue to progress after this combination approach. Genetic changes in the tumor along its growth uncovered by genomic profiling of recurrent and/or metastatic lesions through tumor and/or liquid biopsies may predict the response or resistance to specific agents, suggesting the best therapeutic strategy for each patient by targeting the altered ER-dependent pathway (novel oral SERDs and a new generation of anti-estrogen agents) or alternative ER-independent signaling pathways such as PI3K/AKT/mTOR or tyrosine kinase receptors ( mutations or HER2 low status) or by inhibiting pathways weakened through germline mutations. These agents are being investigated as single molecules and in combination with other target therapies, offering promising weapons to overcome or avoid treatment failure and propose increasingly more personalized treatment approaches. This review presents novel insights into ET and other targeted therapies for managing metastatic HR/HER2 BC by exploring potential strategies based on clinical evidence and genomic profiling following the failure of the CDK4/6i and ET combination.
PubMed: 38930141
DOI: 10.3390/jcm13123611 -
Journal of Personalized Medicine Jun 2024Early-onset colorectal cancer (EOCRC), defined as colorectal cancer in individuals under 50 years of age, has shown an alarming increase in incidence worldwide. We...
Early-onset colorectal cancer (EOCRC), defined as colorectal cancer in individuals under 50 years of age, has shown an alarming increase in incidence worldwide. We report a case of a twenty-four-year-old female with a strong family history of colorectal cancer (CRC) but without an identified underlying genetic predisposition syndrome. Two years after primary surgery and adjuvant chemotherapy, the patient developed new liver lesions. Extensive diagnostic imaging was conducted to investigate suspected liver metastases, ultimately leading to a diagnosis of focal nodular hyperplasia. The young age of the patient has prompted comprehensive genomic and transcriptomic profiling in order to identify potential oncogenic drivers and inform further clinical management of the patient. Besides a number of oncogenic mutations identified in the patient's tumour sample, including KRAS G12D, TP53 R248W and TTN L28470V, we have also identified a homozygous deletion of 24.5 MB on chromosome 8. A multivariate Cox regression analysis of this patient's mutation profile conferred a favourable prognosis when compared with the TCGA COADREAD database. Notably, the identified deletion on chromosome 8 includes the WRN gene, which could contribute to the patient's overall positive response to chemotherapy. The complex clinical presentation, including the need for emergency surgery, early age at diagnosis, strong family history, and unexpected findings on surveillance imaging, necessitated a multidisciplinary approach involving medical, radiation, and surgical oncologists, along with psychological support and reproductive medicine specialists. Molecular profiling of the tumour strongly indicates that patients with complex mutational profile and rare genomic rearrangements require a prolonged surveillance and personalised informed interventions.
PubMed: 38929861
DOI: 10.3390/jpm14060639 -
Cancers Jun 2024Therapeutic advances in oncology in the 21st century have contributed to significant declines in cancer mortality. Notably, targeted therapies comprised the largest... (Review)
Review
Therapeutic advances in oncology in the 21st century have contributed to significant declines in cancer mortality. Notably, targeted therapies comprised the largest proportion of oncology drugs approved by the United States (US) Food and Drug Administration (FDA) over the past 25 years and have become the standard of care for the treatment of many cancers. However, despite the metamorphosis of the therapeutic landscape, some aspects of cancer drug development have remained essentially unchanged. In particular, the dose-finding methodology originally developed for cytotoxic chemotherapy drugs continues to be implemented, even though this approach no longer represents the most appropriate strategy for modern cancer therapies. In recognition of the need to reconsider assumptions, adapt the dose selection process for newer drugs, and design alternative strategies, the FDA has undertaken several initiatives in recent years to address these concerns. These actions include the launch of Project Optimus in 2021 and the issuance of draft guidance for industry on dose optimization of oncology drugs in 2023. Amid this evolving regulatory environment, the present manuscript reviews case studies for six different targeted cancer therapies, highlighting how dose-finding challenges have been managed to date by oncologists, sponsors, and regulators.
PubMed: 38927886
DOI: 10.3390/cancers16122180 -
PAK4-targeted PROTACs in clear cell renal cell carcinoma: a two-for-one targeted and immune therapy?EBioMedicine Jun 2024
PubMed: 38924842
DOI: 10.1016/j.ebiom.2024.105218 -
Journal of Radiation Research Jun 2024We sought to identify potential evidence-practice gaps in palliative radiotherapy using quality indicators (QIs), previously developed using a modified Delphi method....
We sought to identify potential evidence-practice gaps in palliative radiotherapy using quality indicators (QIs), previously developed using a modified Delphi method. Seven QIs were used to assess the quality of radiotherapy for bone metastases (BoM) and brain metastases (BrM). Compliance rate was calculated as the percentage of patients for whom recommended medical care was conducted. Random effects models were used to estimate the pooled compliance rates. Of the 39 invited radiation oncologists, 29 (74%) from 29 centers participated in the survey; 13 (45%) were academic and 16 (55%) were non-academic hospitals. For the QIs, except for BoM-4, the pooled compliance rates were higher than 80%; however, for at least some of the centers, the compliance rate was lower than these pooled rates. For BoM-4 regarding steroid use concurrent with radiotherapy for malignant spinal cord compression, the pooled compliance rate was as low as 32%. For BoM-1 regarding the choice of radiation schedule, the compliance rate was higher in academic hospitals than in non-academic hospitals (P = 0.021). For BrM-3 regarding the initiation of radiotherapy without delay, the compliance rate was lower in academic hospitals than in non-academic hospitals (P = 0.016). In conclusion, overall, compliance rates were high; however, for many QIs, practice remains to be improved in at least some centers. Steroids are infrequently used concurrently with radiotherapy for malignant spinal cord compression.
PubMed: 38923425
DOI: 10.1093/jrr/rrae048 -
Cancer Medicine Jun 2024The CRAFITY score serves as a simple and effective predictive model for individuals diagnosed with hepatocellular carcinoma (HCC) and subjected to treatment with...
BACKGROUND
The CRAFITY score serves as a simple and effective predictive model for individuals diagnosed with hepatocellular carcinoma (HCC) and subjected to treatment with atezolizumab and bevacizumab (Atez/Bev). However, no large sample size studies have reported the application of the CRAFITY score among HCC patients undergoing transarterial chemoembolization (TACE) in conjunction with lenvatinib. This research aims to assess the prognostic role of the CRAFITY score in the context of individuals with HCC receiving TACE in combination with lenvatinib.
METHODS
This retrospective analysis encompassed 314 individuals diagnosed with HCC who underwent the combination of TACE and lenvatinib at two medical facilities in China from August 2019 to August 2022 (comprising a training cohort of n = 172 and a validation cohort of n = 142). We investigated the prognostic values of overall survival (OS), progression-free survival (PFS), disease control rate, and objective response rate in the training cohort based on the CRAFITY scores. Furthermore, the predictive capacity of the model was corroborated through validation using an external cohort.
RESULTS
We included 174 and 142 patients treated with TACE plus lenvatinib in the training and validation cohorts, correspondingly. PFS and OS differed across all three groups in all training and validation cohorts, based on the CRAFITY score (p < 0.001). In both cohorts, the CRAFITY score effectively predicted tumor response (p < 0.001). Moreover, among the 121 patients who received TACE, lenvatinib, and immunotherapy, the CRAFITY score showed promising predictive efficacy in PFS and OS.
CONCLUSIONS
The CRAFITY score, utilizing C-reactive protein and alpha-fetoprotein values, emerges as a dependable and pragmatic instrument for forecasting the effectiveness of TACE plus lenvatinib in individuals with unresectable HCC. This scoring system holds the potential to assist oncologists in making informed clinical decisions.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Chemoembolization, Therapeutic; Quinolines; Phenylurea Compounds; Male; Female; Middle Aged; Retrospective Studies; Aged; Prognosis; Antineoplastic Agents; Adult
PubMed: 38923354
DOI: 10.1002/cam4.7410 -
Current Oncology (Toronto, Ont.) Jun 2024: Death is an unavoidable experience in any person's life and affects not only the dying person but also their caregivers. The dying process has been displaced from...
: Death is an unavoidable experience in any person's life and affects not only the dying person but also their caregivers. The dying process has been displaced from homes to health care facilities in the majority of cases. Facing death and dying has become an everyday life of health care professionals (HCP), especially in palliative care (PC) settings. This study aimed to investigate the death attitudes among HCPs in Serbia. : The Serbian version of the Death Attitude Profile-Revised (DAP-RSp) was used as a measurement instrument. : The average age of the 180 included participants was 42.2 ± 9.9 years; the majority were females (70.0%), with more than 10 years of working experience (73.0%), physicians (70.0%) and those working in a non-oncological (non-ONC) field (57.78%). The mean total score of DAP-RSp was 124.80 ± 22.44. The highest mean score was observed in the neutral acceptance dimension (NA) (5.82 ± 0.90) and lowest in the Escape acceptance (EA) (2.57 ± 1.21). Higher negative death attitudes were reported among nurses compared to physicians ( = 0.002). Statistically significant differences were observed in the fear of death (FD) and death avoidance (DA) domains, favoring PC specialists and oncologists ( = 0.004; = 0.015). Physicians working in Oncology (ONC) showed lower FD values ( = 0.001) compared to non-ONC departments. : Attitudes toward death among HCPs are of great importance for the well-being of both HCPs and patients. Negative attitudes can lead to deficient care. The fear of death is highly represented among Serbian HCPs working in non-ONC fields, including both nurses and physicians. This study emphasizes the need for further research to comprehensively explore and understand HCPs' attitudes toward death. This research highlights the need for the development of an educational curriculum across all levels of medical education, aimed at overcoming the fear of death and enhancing coping strategies, which will improve the care for patients diagnosed with terminal illnesses.
Topics: Humans; Female; Male; Attitude to Death; Adult; Attitude of Health Personnel; Health Personnel; Middle Aged; Serbia; Balkan Peninsula; Surveys and Questionnaires
PubMed: 38920738
DOI: 10.3390/curroncol31060255 -
Current Oncology (Toronto, Ont.) Jun 2024Early integrated palliative care (EIPC) for patients with advanced cancers requires the involvement of family doctors (FDs) and oncologists. We compared attitudes...
Early integrated palliative care (EIPC) for patients with advanced cancers requires the involvement of family doctors (FDs) and oncologists. We compared attitudes between patients and their providers regarding the delivery of EIPC. Patients with newly diagnosed incurable gastrointestinal (GI) cancer at a tertiary cancer centre in Ontario, Canada, were surveyed using a study-specific instrument regarding the importance of and preferences for accessing support across eight domains of palliative care. Physicians within the circle of care completed a parallel survey for each patient. The concordance between patient and physician responses was analyzed. A total of 66 patients were surveyed (median age 69, 35% female). All had an oncologist, 12% had a specialist palliative care provider (SPC), and 97% had an FD, but only 41% listed the FD as part of the care team. In total, 95 providers responded (oncologist = 68, FD = 21, SPC = 6; response rate 92%; 1-3 physician responses per patient). Disease management and physical concerns were most important to patients. Patients preferred to access care in these domains from oncologists or SPCs. For all other domains, most patients attributed primary responsibility to self or family rather than any healthcare provider. Thus, concordance was poor between patient and physician responses. Across most domains of palliative care, we found low agreement between cancer patients and their physicians regarding responsibilities for care, with FDs appearing to have limited involvement at this stage.
Topics: Humans; Palliative Care; Female; Male; Gastrointestinal Neoplasms; Aged; Middle Aged; Prospective Studies; Surveys and Questionnaires; Patient Preference; Attitude of Health Personnel; Aged, 80 and over; Adult; Ontario
PubMed: 38920736
DOI: 10.3390/curroncol31060253 -
Current Oncology (Toronto, Ont.) Jun 2024Although virtual care (VC) has become an integral part of oncology care and healthcare delivery, clinicians' perspectives on and satisfaction with this modality are not...
INTRODUCTION
Although virtual care (VC) has become an integral part of oncology care and healthcare delivery, clinicians' perspectives on and satisfaction with this modality are not well understood.
METHODS
Using a National Network Forum framework and expert panel review, we developed a questionnaire to measure oncologists' satisfaction with VC. The questionnaire was distributed to Canadian oncologists through medical society email lists (n = 1541). We used a 5-point Likert scale to capture their responses, which included strongly disagree (1), disagree (2), undecided (3), agree (4), and strongly agree (5).
RESULTS
A total of 61 oncologists and/or oncology trainees, of 768 (7.9%) who opened their email, completed questionnaires between October 2022 and January 2023. Every questionnaire item had a response rate greater than 98%. Seventy-two percent of the respondents were satisfied with VC. Oncologists who were less comfortable with technology were more likely to report lower levels of satisfaction ( < 0.001, Wilcoxon rank-sum). The questionnaire items that received the highest levels of agreement were related to VC reducing costs and improving access for patients and concerns about missing a diagnosis and assessing patients' functional status. The questionnaire items that received the greatest disagreement were related to VC improving access for patients with language barriers, VC being associated with time-savings for clinicians, improvements in clinical efficacy, and more readily available lab tests.
CONCLUSIONS
Most of the oncologists surveyed are satisfied with VC; however, there are some concerns with VC that need to be addressed. Future research on optimizing VC should address clinicians' concerns, in addition to addressing the patient experience.
Topics: Humans; Surveys and Questionnaires; Oncologists; Telemedicine; Female; Male; Canada; Medical Oncology; Attitude of Health Personnel; Personal Satisfaction; Middle Aged
PubMed: 38920731
DOI: 10.3390/curroncol31060248 -
Current Oncology (Toronto, Ont.) Jun 2024Interest in the oligometastatic prostate cancer (OMPC) is increasing, and various clinical studies have reported the benefits of metastasis-directed radiation therapy...
BACKGROUND
Interest in the oligometastatic prostate cancer (OMPC) is increasing, and various clinical studies have reported the benefits of metastasis-directed radiation therapy (MDRT) in OMPC. However, the recognition regarding the adopted definitions, methodologies of assessment, and therapeutic approaches is diverse among radiation oncologists. This study aims to evaluate the level of agreement for issues in OMPC among radiation oncologists.
METHODS
We generated 15 key questions (KQs) for OMPC relevant to definition, diagnosis, local therapies, and endpoints. Additionally, three clinical scenarios representing synchronous metastatic prostate cancer (mPC) (case 1), metachronous mPC with visceral metastasis (case 2), and metachronous mPC with castration-resistance and history of polymetastasis (case 3) were developed. The 15 KQs were adapted according to each scenario and transformed into 23 questions with 6-9 per scenario. The survey was distributed to 80 radiation oncologists throughout the Republic of Korea. Answer options with 0.0-29.9%, 30-49.9%, 50-69.9%, 70-79.9%, 80-89.9%, and 90-100% agreements were considered as no, minimal, weak, moderate, strong, and near perfect agreement, respectively.
RESULTS
Forty-five candidates voluntarily participated in this study. Among 23 questions, near perfect ( = 4), strong ( = 3), or moderate ( = 2) agreements were shown in nine. For the case recognized as OMPC with agreements of 93% (case 1), near perfect agreements on the application of definitive radiation therapy (RT) for whole metastatic lesions were achieved. While ≥70% agreements regarding optimal dose-fractionation for metastasis-directed RT (MDRT) has not been achieved, stereotactic body RT (SBRT) is favored by clinicians with higher clinical volume.
CONCLUSION
For the case recognized as OMPC, near perfect agreement for the application of definitive RT for whole metastatic lesions was reached. SBRT was more favored as a MDRT by clinicians with a higher clinical volume.
Topics: Male; Humans; Prostatic Neoplasms; Radiation Oncologists; Republic of Korea; Neoplasm Metastasis; Surveys and Questionnaires; Middle Aged
PubMed: 38920729
DOI: 10.3390/curroncol31060245