Radiotherapy treatment modification for prostate cancer patients based on PSMA-PET/CT.

BACKGROUND: Prostate cancer is the most common cancer among men, and its diagnosis and treatment are improving. Our study evaluated how PSMA-PET/CT prior to treatment planning might improve the optimal management of prostate cancer radiotherapy. METHODS: This retrospective pilot study included 43 prostate cancer (PCa) patients referred to our radiation oncologist department, from the urology department, for radiation therapy. 18F-PSMA-PET/CT was ordered by the radiation oncologists mainly due to the lack of resent image staging. The patients were divided into three different groups according to their initially planned treatments: radical radiation therapy (RT) (newly diagnosed PCa patients), salvage RT (patients with biochemical recurrence after radical prostatectomy), or oligometastatic RT (oligometastatic PCa patients with good response after systemic treatment). RESULTS: Following PSMA-PET/CT, the initially planned RT was changed for 60.5% of the patients due to new findings (metastases and/or recurrent disease). The final treatment choice was effected by PSMA-PET/CT outcome in 60.5% (26/43) of the patients, and in 50% (16/32) of patients, the radiation treatment plan changed following PSMA-PET/CT. Only 39.5% (17/43) of the patients who underwent PSMA-PET/CT were treated according to their initial treatment plans. CONCLUSIONS: Our results indicate that PSMA-PET/CT impacts treatment decisions and the selection of RT as well as adjuvant treatment protocols in the management of prostate cancer.

Metastatic Rectal Carcinoma with Long-Term Remission due to Modern Multimodality Treatment.

In the era of personalized medicine, systemic treatment with chemotherapy in combination with targeted drugs, tailored according to RAS and BRAF status, has improved the survival of patients with metastatic colorectal cancer (mCRC), but curative resection of metastases provides the only chance of cure. Here, we present a 40-year-old male with rectal adenocarcinoma and multiple bilateral synchronous liver metastases who has achieved long-term remission with multimodal treatment without resection of all metastatic lesions. This case emphasizes the need of repeated multidisciplinary team assessments and change of treatment intent if extraordinary responses are seen. The initial therapy consisted of short-course radiotherapy and surgery of the primary tumor followed by oxaliplatin-based combination chemotherapy and panitumumab with disease control intent. A complete radiologic response in >20 liver metastases in segments II-VIII was obtained. A biopsy-verified relapse of 3 liver metastases occurred at 9 months of treatment pause. Subsequently, major liver resection of 8 lesions was performed (4 with adenocarcinoma and 4 with cicatrix showing the challenge of disappearing lesions), followed by 6 months of adjuvant-like therapy. No relapse in MRI, PET, or CT has been noted since liver resection 6 years ago. Comprehensive genomic profiling of the primary tumor and liver metastases had similar driver mutations representing a low level of gene alteration and low diversity, possibly explaining the exceptional treatment response.

Gene-Guided Treatment Decision-Making in Non-Small Cell Lung Cancer - A Systematic Review.

Decision-making in cancer treatment is part of clinicians' everyday work, and it is especially challenging in non-small cell lung cancer (NSCLC) patients, for whom decisions are clearly dependent on gene alterations or the lack of them. The multimodality of treatments, involvement of gene alterations in defining systemic cancer therapies, and heterogeneous nature of tumors and their responsiveness provide extra challenges. This article reviews the existing literature to 2021 with extra effort to explore the role of genes and gene-driven therapies as part of decision-making. The process and elements in this decision-making participation are recognized and discussed comprehensively. Genetic health literacy aids are provided as a part of the review. Our systematic review, data extraction and analysis found that with current methods and broad gene panels, patients benefit from early molecular testing of liquid biopsy samples. An estimated 79% of liquid biopsy samples showed somatic mutations based on 8 original studies included in the systematic review. When both liquid biopsy samples and tissue samples are evaluated, the sensitivity to detect targetable mutations in NSCLC increases. We recommend early testing with liquid biopsy. Additional effort is needed for the logistics of obtaining and evaluating samples, and tissue samples should be saved and stored for tests that are not possible from liquid biopsy.

Current challenges in applying gene-driven therapies in clinical lung cancer practice.

Over the last twenty years, with the development of gene-driven therapies, numerous new drugs have entered clinical use. Very few of these new drugs are suitable for a large number of patients, and all require molecular genetic testing. In lung cancer, gene-targeted therapy has evolved rapidly and has placed demands on the development of diagnostics and tissue sample preparation and logistics. Rapid diagnosis and prevalence assessment are necessary to determine the prognosis of a lung cancer patient based on the latest research findings. Therefore, the molecular-genetic diagnostic pathway must also be accelerated and matured to do the necessary analyses on small samples. Because lung cancer rebiopsy can be difficult, liquid biopsy techniques should be developed to cover more of the treatable mutations. There are obstacles related to tissue sampling, new genomic techniques and access to gene-driven cancer drugs, including their affordability. With this review and case study, we go into the obstacles faced by our clinic and discuss how to tackle these obstacles in lung cancer. We use lung cancer as an example due to its complexity, though these same obstacles are found in different cancers on a minor scale.

Preemptive screening of DPYD as part of clinical practice: high prevalence of a novel exon 4 deletion in the Finnish population.

Capecitabine is a fluoropyrimidine that is widely used as a cancer drug for the treatment of patients with a variety of cancers. Unfortunately, early onset, severe or life-threatening toxicity is observed in 19-32% of patients treated with capecitabine and 5FU. Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme in the degradation of 5FU and a DPD deficiency has been shown to be a major determinant of severe fluoropyrimidine-associated toxicity. DPD is encoded by the DPYD gene and some of the identified variants have been described to cause DPD deficiency. Preemptive screening for DPYD gene alterations enables the identification of DPD-deficient patients before administering fluoropyrimidines. In this article, we describe the application of upfront DPD screening in Finnish patients, as a part of daily clinical practice, which was based on a comprehensive DPYD gene analysis, measurements of enzyme activity and plasma uracil concentrations. Almost 8% of the patients (13 of 167 patients) presented with pathogenic DPYD variants causing DPD deficiency. The DPD deficiency in these patients was further confirmed via analysis of the DPD activity and plasma uracil levels. Interestingly, we identified a novel intragenic deletion in DPYD which includes exon 4 in four patients (31% of patients carrying a pathogenic variant). The high prevalence of the exon 4 deletion among Finnish patients highlights the importance of full-scale DPYD gene analysis. Based on the literature and our own experience, genotype preemptive screening should always be used to detect DPD-deficient patients before fluoropyrimidine therapy.

Recent clinical evidence on metronomic dosing in controlled clinical trials: a systematic literature review.

Introduction: Metronomic dosing is used to give continuous chemotherapy at low doses. The low doses have minimal side effects and may enable cancer treatment to be remodeled toward the management of chronic disease.Methods: We searched PubMed database to obtain relevant clinical trials studying metronomic chemotherapy (MCT). Our main focus was to find controlled phase II and phase III trials.Results: This systematic review summarizes the results of 91 clinical reports focusing on randomized phase II and phase III clinical studies between 2012 and 2018. During that time, nine randomized phase II and 10 randomized phase III studies were published. In the majority of the studies, MCT was well tolerated, and major side effects were rarely seen. Altogether, 4 phase III studies and 4 randomized phase II studies presented positive results and some clinical benefit.Discussion: Most of the studies did not show significantly improved overall survival or progression-free survival. Typically, the metronomic dosing was explored in a maintenance setup and was added to other agents given within normal high doses, whereas no trial was performed challenging metronomic dosing and best supportive care in later treatment lines. Therefore, there is no definite evidence on the efficacy of single metronomic dosing and firm evidence of metronomic dosing is still missing. There is a need for further confirmation of the usefulness of this approach in clinical practice.

The Value of Liquid Biopsies for Guiding Therapy Decisions in Non-small Cell Lung Cancer.

Targeted therapies have allowed for an individualized treatment approach in non-small-cell lung cancer (NSCLC). The initial therapeutic decisions and success of targeted therapy depend on genetic identification of personal tumor profiles. Tissue biopsy is the gold standard for molecular analysis, but non-invasive or minimally invasive liquid biopsy methods are also now used in clinical practice, allowing for later monitoring and optimization of the cancer treatment. The inclusion of liquid biopsy in the management of NSCLC provides strong evidence on early treatment response, which becomes a basis for determining disease progression and the need for changes in treatment. Liquid biopsies can drive the decision making for treatment strategies to achieve better patient outcomes. Cell-free DNA and circulating tumor cells obtained from the blood are promising markers for determining patient status. They may improve cancer treatments, allow for better treatment control, enable early interventions, and change decision making from reactive actions toward more predictive early interventions. This review aimed to present current knowledge on and the usefulness of liquid biopsy studies in NSCLC from the perspective of how it has allowed individualized treatments according to gene profiling and how the method may alter the treatment decisions in the future.

Potential of Liquid Biopsies for Breast Cancer Screening, Diagnosis, and Response to Treatment.

Cancer therapy decisions are often made according to the histopathological-molecular profile of tumor tissue obtained from surgery or biopsy. It has been shown that tumor profiles change with time and treatment, and that tumor tissue is heterogeneous. Thus, other approaches that are easily accessible and less invasive than surgery or biopsy to monitor responses to treatment and predict relapses are urgently needed. In the last few years, the term "liquid biopsies" has been introduced to represent multifunctional circulating biomarkers in the peripheral blood and other physiological fluids of patients with cancer. Liquid biopsies are a noninvasive alternative to tissue biopsies, but they have not been implemented in routine clinical practice for breast cancer. In addition, liquid biopsies seem to be a promising approach for personalized medicine, which enables the prediction, monitoring, and rational selection of appropriate therapy for individual patients. In this review, we outline recent progress and current challenges with liquid biopsies in clinical practice for breast cancer diagnosis, treatment choices, and responses to therapy from a clinician's perspective.

Human Metaplastic Breast Carcinoma and Decorin.

Metaplastic breast carcinoma (MBC) is a rare subtype of invasive breast cancer and has poor prognosis. In general, cancers are heterogeneous cellular masses comprised of different cell types and their extracellular matrix (ECM). However, little is known about the composition of the ECM and its constituents in MBC. Decorin is a ubiquitous ECM macromolecule known of its oncosuppressive activity. As such, it provides an intriguing molecule in the development of novel therapeutics for different malignancies such as MBC. In this study, decorin immunoreactivity and the effect of adenoviral decorin cDNA (Ad-DCN) transduction were examined in MBC. Multiple immunohistochemical stainings were used to characterize a massive breast tumour derived from an old woman. Furthermore, three-dimensional (3D) explant cultures derived from the tumour were transduced with Ad-DCN to study the effect of the transduction on the explants. The MBC tumour was shown to be completely negative for decorin immunoreactivity demonstrating that the malignant cells were not able to synthesize decorin. Ad-DCN transduction resulted in a markedly altered cytological phenotype of MBC explants by decreasing the amount of atypical cells and by inhibiting cell proliferation. The results of this study support approaches to develop new, decorin-based adjuvant therapies for MBC.