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1.
When dormancy fuels tumour relapse.
Santos-de-Frutos, K, Djouder, N
Communications biology. 2021;(1):747
Abstract
Tumour recurrence is a serious impediment to cancer treatment, but the mechanisms involved are poorly understood. The most frequently used anti-tumour therapies-chemotherapy and radiotherapy-target highly proliferative cancer cells. However non- or slow-proliferative dormant cancer cells can persist after treatment, eventually causing tumour relapse. Whereas the reversible growth arrest mechanism allows quiescent cells to re-enter the cell cycle, senescent cells are largely thought to be irreversibly arrested, and may instead contribute to tumour growth and relapse through paracrine signalling mechanisms. Thus, due to the differences in their growth arrest mechanism, metabolic features, plasticity and adaptation to their respective tumour microenvironment, dormant-senescent and -quiescent cancer cells could have different but complementary roles in fuelling tumour growth. In this review article, we discuss the implication of dormant cancer cells in tumour relapse and the need to understand how quiescent and senescent cells, respectively, may play a part in this process.
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Chemoprevention of colorectal cancer: Past, present, and future.
Umezawa, S, Higurashi, T, Komiya, Y, Arimoto, J, Horita, N, Kaneko, T, Iwasaki, M, Nakagama, H, Nakajima, A
Cancer science. 2019;(10):3018-3026
Abstract
Chemoprevention began to be considered as a potential strategy for lowering the incidence of cancer and cancer-related deaths in the 1970s. For clinical chemoprevention trials against cancer, including colorectal cancer (CRC), well-established biomarkers are necessary for use as reliable endpoints. Difficulty in establishing validated biomarkers has delayed the start of CRC chemoprevention development. Chemoprevention trials for CRC have only recently been initiated thanks to the identification of reliable biomarkers, such as colorectal adenomas and aberrant crypt foci. Some promising agents have been developed for the prevention of CRC. The chemopreventive effect of selective cyclooxygenase 2 inhibitors has been shown, although these inhibitors are associated with cardiovascular toxicity as a crucial adverse effect. Aspirin, which is a unique agent among non-steroidal anti-inflammatory drugs (NSAIDs) showing minimal gastrointestinal toxicity and no cardiovascular risk, has prevented adenoma recurrence in some randomized controlled trials. More recently, metformin, which is a first-line oral medicine for type 2 diabetes, has been shown to be safe and to prevent adenoma recurrence. A recommendation of the United States Preventive Services Task Force published in 2016 provides a Grade B recommendation for the use of aspirin for chronic prophylaxis against diseases, including CRC, in certain select populations. However, the roles of other agents have yet to be determined, and investigations to identify novel "post-aspirin" agents are also needed. The combined use of multiple drugs, such as aspirin and metformin, is another option that may lead not only to stronger CRC prevention, but also to improvement of other obesity-related diseases.
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Bridging the Imaging Gap: PSMA PET/CT Has a High Impact on Treatment Planning in Prostate Cancer Patients with Biochemical Recurrence-A Narrative Review of the Literature.
Ekmekcioglu, Ö, Busstra, M, Klass, ND, Verzijlbergen, F
Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2019;(10):1394-1398
Abstract
68Ga- and 18F-labeled prostate-specific membrane antigen (PSMA) molecules have created new opportunities for the unmet diagnostic needs in prostate cancer. The purpose of this article is to give an overview of studies that have examined the role of PSMA PET in treatment planning for prostate cancer patients with biochemical recurrence (BCR). Methods: Medline, Embase, Web of Science, Google Scholar, and Cochrane Central were searched for relevant articles. After excluding the articles that did not fulfill the required criteria, we included in this review 12 publications that reported the impact of PSMA PET on the treatment plan for prostate cancer patients with BCR. Results: All studies in our review emphasized the impact of PSMA PET images on therapy management in prostate cancer patients with BCR. Overall, the impact of PSMA PET/CT on therapy management varied between 30% and 76% among the 1,346 patients included in the review. Upstaging was reported in 32%-67% of the patients. Patients with low prostate-specific antigen values (<0.5 ng/mL) also demonstrated positive lesions, which could not have been detected by means of conventional imaging techniques. Important modifications to the original treatment plan included avoidance of systemic therapy (17%-40%) and PET-directed local therapy (in ≤60% of the patients). Conclusion: PSMA imaging demonstrated a high clinical impact in patients with BCR, with modifications to the original treatment plan occurring among half the patients. Detecting recurrence in BCR can prevent unnecessary toxicity and lead to individualized therapy.
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4.
Impact of dietary patterns and the main food groups on mortality and recurrence in cancer survivors: a systematic review of current epidemiological literature.
Jochems, SHJ, Van Osch, FHM, Bryan, RT, Wesselius, A, van Schooten, FJ, Cheng, KK, Zeegers, MP
BMJ open. 2018;(2):e014530
Abstract
OBJECTIVE To determine whether there is an association between dietary patterns/indices and foods from the main food groups (highest vs lowest intakes) prior to or after cancer diagnosis and mortality and cancer recurrence in cancer survivors. PARTICIPANTS Survivors of common cancers with a 10-year survival rate of ≥50%: bladder, bowel, breast, cervical, kidney, laryngeal, prostate, testicular, uterine cancer, malignant melanoma and (non-)Hodgkin's lymphoma. OUTCOME MEASURES Mortality (overall, cancer-specific, from other causes) and cancer recurrence. INFORMATION SOURCES PubMed, Embase and the Cochrane Library were searched from inception to April 2017. Additional studies were identified by searching reference lists. Two authors independently screened titles and abstracts, assessed study quality and extracted the data. RESULTS A total of 38 studies were included. The risk of bias was rated low for the included randomised controlled trials (RCTs) and moderate for the cohort studies. The quality of evidence was assessed with the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach and was rated moderate (RCTs), and (very)low (cohort studies). Reducing the amount of fat after diagnosis appears to decrease the risk of breast cancer recurrence. Adherence to a high-quality diet and prudent diet after diagnosis appears to decrease the risk of death from other causes (and overall mortality for high-quality diet) in breast cancer survivors. Adherence to a Western diet, before and after diagnosis, appears to increase the risk of overall mortality and death from other causes among breast cancer survivors. Evidence from studies among other cancer survivors was too limited or could not be identified. CONCLUSION For many cancer survivors, there is little evidence to date to indicate that particular dietary behaviours influence outcomes with regard to recurrence and mortality. Notwithstanding, limited evidence suggests that a low-fat diet, a high-quality diet and a prudent diet are beneficial for breast cancer survivors, while a Western diet is detrimental for breast cancer survivors.
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Cells to prevent/treat relapse following allogeneic stem cell transplantation.
Dietz, AC, Wayne, AS
Hematology. American Society of Hematology. Education Program. 2017;(1):708-715
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Abstract
Relapse of cancer remains one of the primary causes of treatment failure and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). A multitude of approaches have been used in the management of posttransplant relapse. This review focuses on recent data with cellular therapies designed to treat or prevent posttransplant relapse of hematologic malignancies, although many of these therapeutic approaches also have applications to solid tumors and in the nontransplant setting. Currently available cell therapies include second transplant, natural killer cells, monocyte-derived dendritic cell vaccines, and lymphocytes via donor lymphocyte infusion, antigen-primed cytotoxic T lymphocytes, cytokine-induced killer cells, marrow-infiltrating lymphocytes, and chimeric antigen receptor T cells. These treatment options offer the prospect for improved relapse-free survival after HSCT.
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Large enchondroma of the thoracic spine: a rare case report and review of the literature.
Guo, J, Gao, JZ, Guo, LJ, Yin, ZX, He, EX
BMC musculoskeletal disorders. 2017;(1):155
Abstract
BACKGROUND Enchondroma, a subtype of chondroma, originates from the medullary cavity of the bone and produces an expansile growth pattern. Enchondroma located in the spine is rare and a few cases of large thoracic enchondroma have been reported. The authors document a rare case of large enchondroma in the thoracic spine of a 49-year-old woman, and discuss its clinical, radiological and histopathological characteristics. CASE PRESENTATION The patient presented with rapidly progressive and severe pain on her upper back. Magnetic resonance imaging revealed an expansile lesion at the posterior elements of T3 that was hypointense on T1-weighted images and mixed iso- to hyperintense on T2-weighted images. Administration of gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) resulted in heterogeneous enhancement. During surgery, a large tumor of 4.2cm × 4.7cm × 2.1cm was resected along with the lamina and spinous process. Histological examination revealed that the tumor consisted of mature hyaline cartilage with typical chondrocytes, indicating that it was an enchondroma. CONCLUSIONS Despite its benign-growing nature, enchondroma should be examined closely for signs of enchondromatosis and enchondrosarcoma. Complete surgical resection is the treatment of choice for immediate relief of symptoms and avoidance of recurrence.
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Ocular oncology: advances in retinoblastoma, uveal melanoma and conjunctival melanoma.
Vasalaki, M, Fabian, ID, Reddy, MA, Cohen, VM, Sagoo, MS
British medical bulletin. 2017;(1):107-119
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Abstract
BACKGROUND Retinoblastoma, uveal and conjunctival melanomas are important malignancies within the remit of ocular oncology. Outlined are the diagnostic features and management principles, as well as advancements in the field and current challenges. SOURCES OF DATA Original papers, reviews and guidelines. AREAS OF AGREEMENT Most eyes with retinoblastoma (International Intraocular Retinoblastoma Classification (IIRC) Group A-D) are salvaged, whereas advanced cases (Group E) remain a challenge. Despite a high rate of local tumour control in uveal melanoma, metastatic spread commonly occurs. Conjunctival melanoma is treated by complete resection, but high rates of local recurrence occur, with the possibility of systemic relapse and death. AREAS OF CONTROVERSY Use of the IIRC in retinoblastoma, and systemic screening in melanomas. GROWING POINTS Utilization of novel treatment modalities in retinoblastoma and an increasing understanding of the genetic basis of melanomas. AREAS TIMELY FOR DEVELOPING RESEARCH Improvements in chemotherapy delivery in retinoblastoma and prognostic tests in melanomas.
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8.
Reducing Breast Cancer Recurrence: The Role of Dietary Polyphenolics.
Braakhuis, AJ, Campion, P, Bishop, KS
Nutrients. 2016;(9)
Abstract
Evidence from numerous observational and clinical studies suggest that polyphenolic phytochemicals such as phenolic acids in olive oil, flavonols in tea, chocolate and grapes, and isoflavones in soy products reduce the risk of breast cancer. A dietary food pattern naturally rich in polyphenols is the Mediterranean diet and evidence suggests those of Mediterranean descent have a lower breast cancer incidence. Whilst dietary polyphenols have been the subject of breast cancer risk-reduction, this review will focus on the clinical effects of polyphenols on reducing recurrence. Overall, we recommend breast cancer patients consume a diet naturally high in flavonol polyphenols including tea, vegetables (onion, broccoli), and fruit (apples, citrus). At least five servings of vegetables and fruit daily appear protective. Moderate soy protein consumption (5-10 g daily) and the Mediterranean dietary pattern show the most promise for breast cancer patients. In this review, we present an overview of clinical trials on supplementary polyphenols of dietary patterns rich in polyphenols on breast cancer recurrence, mechanistic data, and novel delivery systems currently being researched.
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Focal salvage therapy for local prostate cancer recurrences after primary radiotherapy: a comprehensive review.
Duijzentkunst, DA, Peters, M, van der Voort van Zyp, JR, Moerland, MA, van Vulpen, M
World journal of urology. 2016;(11):1521-1531
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Abstract
BACKGROUND/AIM: Patients with locally recurrent prostate cancer after primary radiotherapy can be eligible for salvage treatment. Whole-gland salvage techniques carry a high risk of toxicity. A focal salvage approach might reduce the risk of adverse events while maintaining cancer control in carefully selected patients. The aim of this review was to evaluate current literature to assess whether focal salvage leads to a comparable or favourable recurrence rate and less toxicity compared to whole-gland salvage. METHODS A literature search was performed using PubMed, Embase and the Cochrane Library. A total of 3015 articles were screened and assessed for quality. Eight papers [on focal cryoablation (n = 3), brachytherapy (n = 3) and high-intensity focused ultrasound (n = 2)] were used to report outcomes. RESULTS One-, 2-, 3- and 5-year biochemical disease-free survival (BDFS) ranges for focal salvage are, respectively, 69-100, 49-100, 50-91 and 46.5-54.5 %. Severe genitourinary, gastrointestinal and sexual function toxicity rates are 0-33.3 %. One study directly compares focal to whole-gland salvage cryotherapy, showing 5-year BDFS of, respectively, 54.4 and 86.5 % with lower toxicity rates for focal salvage patients. CONCLUSION Provisional data suggest that BDFS rates of focal salvage are in line with those of whole-gland approaches. There is evidence that focal salvage could decrease severe toxicity and preserve erectile function.
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Panoptic clinical review of the current and future treatment of relapsed/refractory T-cell lymphomas: Cutaneous T-cell lymphomas.
Zinzani, PL, Bonthapally, V, Huebner, D, Lutes, R, Chi, A, Pileri, S
Critical reviews in oncology/hematology. 2016;:228-40
Abstract
Primary cutaneous T-cell lymphomas (CTCLs), such as mycosis fungoides and Sézary syndrome, are a rare group of non-Hodgkin lymphomas, usually treated using a multimodal approach. Unfortunately, many patients go on to develop relapsed/refractory disease. Systemic treatment for relapsed/refractory CTCL has historically relied on chemotherapies and interferons, and while active, responses are often short-lived. Three drugs are now approved in the US to treat relapsed/refractory CTCL including the oral retinoid, bexarotene, and histone deacetylase inhibitors, romidepsin and vorinostat. Although response rates are typically <35%, romidepsin and vorinostat can induce some durable responses in heavily pretreated patients and alleviate bothersome symptoms, such as pruritus. New studies indicate that the anti-CD30 antibody-drug conjugate brentuximab vedotin, anti-CCR4 antibody mogamulizumab, and fusion protein immunotoxin A-dmDT390-bisFv(UCHT1) may be particularly active in this setting. In this paper, we present an exhaustive review of the clinical data on current and possible future drug treatment options for relapsed/refractory CTCL.