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2.
Expert Rev Anticancer Ther ; 24(5): 219-227, 2024 May.
Article in English | MEDLINE | ID: mdl-38526540

ABSTRACT

INTRODUCTION: The outcome of patients with metastatic colorectal cancer (mCRC) has improved significantly in the last few decades. Metastatic colorectal cancer is a highly heterogenous cancer. Beyond second line chemotherapy, treatment decisions are often based on molecular testing. METHOD: In this narrative review, we provide a comprehensive summary of data from key clinical trials and discuss how to integrate these agents into the current treatment landscape of metastatic colorectal cancer. EXPERT OPINION: In the era of precision medicine, molecular testing plays an increasingly important role in the management of mCRC. Efforts need to be made to target treatment based on molecular test results.


Subject(s)
Colorectal Neoplasms , Molecular Targeted Therapy , Neoplasm Metastasis , Precision Medicine , Humans , Colorectal Neoplasms/pathology , Colorectal Neoplasms/drug therapy , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/pharmacology
3.
Pediatr Dev Pathol ; 27(3): 266-269, 2024.
Article in English | MEDLINE | ID: mdl-38178317

ABSTRACT

Serous cystadenoma is a rare lesion in the para-testicular tissue, with even rarer reports of this entity occurring in the scrotum post-orchidopexy. We present such an occurrence, adding support for its existence as a distinct entity.


Subject(s)
Cystadenoma, Serous , Genital Neoplasms, Male , Orchiopexy , Scrotum , Humans , Male , Scrotum/pathology , Cystadenoma, Serous/pathology , Cystadenoma, Serous/diagnosis , Cystadenoma, Serous/surgery , Genital Neoplasms, Male/pathology , Genital Neoplasms, Male/diagnosis , Genital Neoplasms, Male/surgery , Mullerian Ducts/pathology , Mullerian Ducts/abnormalities
4.
Expert Rev Anticancer Ther ; 23(12): 1237-1249, 2023.
Article in English | MEDLINE | ID: mdl-37842857

ABSTRACT

INTRODUCTION: Prognosis of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) remains disappointing with a 5-year overall survival of only 3-5%. Compared to other cancers, the evolution in standard therapeutic options has been stagnant and polychemotherapy regimens (with well-known toxicity profile and resistance pattern) remain standard of care. Only for patients (5%-7%) with a breast cancer gene (BRCA) pathogenic germline variant, prognosis has improved by the use of olaparib (poly-ADP ribose polymerase (PARP) inhibitor). AREAS COVERED: This review covers emerging treatment strategies in the management of mPDAC. One of the main topics is the rigid and immunological cold tumor microenvironment (TME) of PDAC and the search for agents that impact this TME and/or engage the immune system. In addition, the use of next-generation sequencing (NGS) has elicited for some patients new targeted therapies directed at alterations in the RTK/RAS/MAPK pathway and the deoxyribonucleic acid (DNA) damage repair pathway. Other evolving treatment strategies are also discussed. EXPERT OPINION: The search for new, often combination, treatment strategies for mPDAC should be encouraged and implemented in early treatment lines given the significant decline of performance status of patients in later lines. NGS analysis should be used where available, although cost-effectiveness could be debatable.


Subject(s)
Pancreatic Neoplasms , Poly(ADP-ribose) Polymerase Inhibitors , Humans , Poly(ADP-ribose) Polymerase Inhibitors/pharmacology , Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/genetics , Prognosis , Poly(ADP-ribose) Polymerases/metabolism , Tumor Microenvironment
5.
Target Oncol ; 17(2): 95-110, 2022 03.
Article in English | MEDLINE | ID: mdl-35290591

ABSTRACT

Gastrointestinal stromal tumours (GISTs) are the most common gastrointestinal tract mesenchymal tumours. Tyrosine kinase inhibitors (TKIs) have transformed the management of advanced GIST. Imatinib was the first TKI to gain approval as management for patients with advanced GIST, establishing a new standard of care. Since then, as a result of several trials including the GRID and INVICTUS studies, we now have five lines of approved targeted therapy, including imatinib, sunitinib, regorafenib, ripretinib and avapritinib for the treatment of unresectable, advanced GISTs. In this review, the Australasian Gastrointestinal Trials Group (AGITG) provide an overview of the key trials that have changed clinical practice, discuss the molecular drivers of GISTs, the importance of molecular testing and directing therapy according to molecular targets, as well as future strategies in the management of advanced GISTs.


Subject(s)
Antineoplastic Agents , Gastrointestinal Neoplasms , Gastrointestinal Stromal Tumors , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Gastrointestinal Neoplasms/drug therapy , Gastrointestinal Neoplasms/pathology , Gastrointestinal Stromal Tumors/drug therapy , Humans , Imatinib Mesylate/pharmacology , Imatinib Mesylate/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Sunitinib/therapeutic use
6.
Fam Cancer ; 21(3): 357-362, 2022 07.
Article in English | MEDLINE | ID: mdl-34519924

ABSTRACT

FH Tumour Predisposition Syndrome, also known as Hereditary Leiomyomatosis and renal cell cancer (HLRCC), or Reed Syndrome, is an autosomal dominant condition clinically characterized by multiple cutaneous leiomyomas, multiple early-onset uterine leiomyomas and early-onset renal cell cancer. Here we report a young female with FH Tumour Predisposition Syndrome with no clinical features except early-onset uterine leiomyomas. Whilst there is a significant history of uterine leiomyomas in her family, there is no history of cutaneous leiomyomas or renal cell cancer (RCC). Uterine leiomyomatosis in young adults may represent a narrow phenotypic variant of FH Tumour Predisposition Syndrome. It is important that young women who present with multiple leiomyomata or leiomyomata with atypical features are referred for molecular genetic testing.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Leiomyomatosis , Neoplastic Syndromes, Hereditary , Skin Neoplasms , Uterine Neoplasms , Adolescent , Carcinoma, Renal Cell/genetics , Female , Fumarate Hydratase/genetics , Genetic Predisposition to Disease , Humans , Kidney Neoplasms/genetics , Leiomyomatosis/genetics , Leiomyomatosis/pathology , Neoplastic Syndromes, Hereditary/genetics , Neoplastic Syndromes, Hereditary/pathology , Skin Neoplasms/genetics , Skin Neoplasms/pathology , Uterine Neoplasms/genetics , Uterine Neoplasms/pathology , Young Adult
9.
Genes Chromosomes Cancer ; 60(5): 385-397, 2021 05.
Article in English | MEDLINE | ID: mdl-33382149

ABSTRACT

Poly (ADP-ribose) polymerase (PARP) inhibitors have transformed the management of recurrent ovarian cancer in patients with BRCA-mutations and beyond. Olaparib was the first PARP inhibitor to gain approval as maintenance therapy for patients with newly diagnosed, advanced BRCA-mutated ovarian cancer establishing a new standard of care. At the end of 2020, as a result of the SOLO1, PRIMA, and PAOLA-1 phase III trials, we are now in an era where three maintenance PARP inhibitor strategies have FDA and European Medicines Agency approval in the first-line setting. In this review, we provide an overview of the key PARP inhibitor trials that have changed clinical practice, discuss directing therapy according to biomarker status (BRCA and homologous recombination deficiency) and future strategies in ovarian cancer and other gynecological malignancies.


Subject(s)
Ovarian Neoplasms/drug therapy , Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use , Clinical Trials as Topic , Female , Humans , Poly(ADP-ribose) Polymerase Inhibitors/administration & dosage , Poly(ADP-ribose) Polymerase Inhibitors/adverse effects , Practice Guidelines as Topic
10.
BMJ Case Rep ; 13(7)2020 Jul 22.
Article in English | MEDLINE | ID: mdl-32699060

ABSTRACT

Despite the increasing incidence of metastatic melanoma in the older population, there are relatively limited data for those older than 75 years of age. Elderly patients are often under-represented in clinical trials. In addition, elderly patients in trials often have a lower Eastern Cooperative Oncology Group score and fewer comorbidities and may thus not truly reflect the realities of day-to-day clinical practice. We present a case of a 95-year-old woman who had extensive and unresectable subcutaneous and dermal deposits of metastatic melanoma of her right leg, which caused oedema and reduced mobility. She was treated concurrently with pembrolizumab and radiotherapy to her leg lesions of melanoma. She has had an excellent response to treatment, with complete resolution of the subcutaneous and dermal metastatic deposits and has not developed any immune-related toxicities. Our experience demonstrates that anti-programmed-death-receptor-1 therapy can be given safely and effectively even in very elderly metastatic melanoma patients.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Agents, Immunological/therapeutic use , Immunotherapy/methods , Melanoma/complications , Neoplasm Metastasis/drug therapy , Skin Neoplasms/complications , Aged, 80 and over , Female , Humans , Treatment Outcome
11.
Drugs Aging ; 37(6): 411-423, 2020 06.
Article in English | MEDLINE | ID: mdl-32307654

ABSTRACT

Despite the increasing incidence of metastatic melanoma in the older population, there is relatively limited specific data surrounding the use of immunotherapy for the treatment of advanced melanoma for patients above the age of 65 years. To date, there has not been a prospective trial done to evaluate the safety and efficacy of using immunotherapy to treat older patients with advanced melanoma. Older patients are often under-represented in clinical trials. In addition, older patients in clinical trials may have lower Eastern Cooperative Oncology Group (ECOG) performance score and fewer co-morbidities, and thus trial data may not truly reflect the experience of treating older patients. The purpose of this descriptive review is to examine the efficacy and safety data of the three currently approved immune checkpoint inhibitors for advanced melanoma treatment in older patients. Our review of available data established that the efficacy and tolerability of immunotherapy in older patients are comparable to results seen in younger patients. However, a dedicated, prospective, randomised trial to assess the safety, tolerability, and quality-of-life parameters of immunotherapy in the older population would provide further insight on the value of these treatments.


Subject(s)
Immunotherapy/methods , Melanoma/pathology , Melanoma/therapy , Aged , Humans , Immunotherapy/adverse effects , Melanoma/immunology , Randomized Controlled Trials as Topic , Safety
12.
Diagn Cytopathol ; 47(8): 817-820, 2019 Aug.
Article in English | MEDLINE | ID: mdl-30963729

ABSTRACT

A 57-year old man presented with a 3.6 cm submucosal rectal cystic mass detected on colonoscopy and MRI. The lesion was deroofed, with rectal cyst fluid and cyst wall received for examination. Smears contained atypical cells occurring singly and in small aggregates, with epithelioid and spindled cells with hyperchromatic nuclei. Occasional cells exhibited intranuclear cytoplasmic inclusions. The concurrent histopathology specimen from the rectal cyst wall showed good correlation with the cytologic findings. The lesion was confined to the muscularis propria, with predominantly epithelioid cells and occasional spindled forms arranged in sheets, nests, and trabeculae with intervening fibrillary and fibrous stroma. Mitotic figures were scant, with no atypical mitoses or necrosis. An extensive immunohistochemical panel was performed, showing strong and diffuse nuclear and cytoplasmic staining with S100 and moderate to strong intensity nuclear staining with SOX10, in keeping with a benign epithelioid peripheral nerve sheath tumour. The patient remains well 3 years following diagnosis, and two subsequent biopsies at the site show no evidence of recurrent disease. We herein provide the first cytologic description of this lesion, with histopathologic correlation and a brief review of other differential diagnostic possibilities.


Subject(s)
Cytodiagnosis/methods , Epithelioid Cells/pathology , Nerve Sheath Neoplasms/pathology , Peripheral Nervous System Neoplasms/pathology , Rectal Neoplasms/pathology , Body Fluids/cytology , Cysts/pathology , Humans , Male , Middle Aged
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