ABSTRACT

INTRODUCTION: Breast cancer treated with adjuvant hypofractionation radiotherapy with two different techniques, i.e., volumetric-modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT) and their effects in terms of loco-regional control and adverse effects in terms of cutaneous, pulmonary, and cardiac outcomes are compared.

MATERIALS AND METHODS: This is a prospective non-randomized observational study. VMAT and IMRT plan for 30 breast cancer patients who were supposed to receive adjuvant radiotherapy were prepared using a hypofractionation schedule. The plans were dosimetrically evaluated.

OBJECTIVE: Dosimetric comparative analysis of IMRT and VMAT in hypofractionated radiotherapy in breast cancer is done and tested whether VMAT has a dosimetric advantage over IMRT. These patients were recruited for a clinical assessment of toxicities. They were followed up for at least three months.

RESULT: On dosimetric analysis, planning target volume (PTV) coverage (PTV_ V95) of both VMAT (96.41 ± 1.31) and IMRT (96.63 ± 1.56) were similar with significantly lower monitor units required with VMAT plans (1,084.36 ± 270.82 vs 1,181.55 ± 244.50, p = 0.043). Clinically, all patients tolerated hypofractionation through VMAT (n = 8) and IMRT (n = 8) satisfactorily in the short term. No cardiotoxicity or appreciable falls in pulmonary function test parameters were observed. Acute radiation dermatitis poses challenges similar to standard fractionation or any other delivery technique.

CONCLUSION: PVT dose, homogeneity, and conformity indices were similar in both VMAT and IMRT groups. In VMAT, there was high-dose sparing of some critical organs like the heart and lungs at the cost of the low-dose baths to these organs. Increased risk of secondary cancer will require a decade-long follow-up study to indict the VMAT technique. As we move toward precision in oncology, "one-size-fits-all" can never be an acceptable dictum. Each patient is unique and therefore we must offer, and the patient must "choose wisely."

PMID:37228558 | PMC:PMC10206676 | DOI:10.7759/cureus.38045

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PubMed articles on: Cardio-Oncology

Editorial: Cardio-oncology and reverse cardio-oncology: the manifold interconnections between heart failure and cancer

Front Physiol. 2023 May 9;14:1205810. doi: 10.3389/fphys.2023.1205810. eCollection 2023.

NO ABSTRACT

PMID:37228811 | PMC:PMC10203590 | DOI:10.3389/fphys.2023.1205810

17:27

PubMed articles on: Cardio-Oncology

PDE10A Inactivation Prevents Doxorubicin-Induced Cardiotoxicity and Tumor Growth

Circ Res. 2023 May 26. doi: 10.1161/CIRCRESAHA.122.322264. Online ahead of print.

ABSTRACT

BACKGROUND: Cyclic nucleotides play critical roles in cardiovascular biology and disease. PDE10A (phosphodiesterase 10A) is able to hydrolyze both cAMP and cGMP. PDE10A expression is induced in various human tumor cell lines, and PDE10A inhibition suppresses tumor cell growth. Chemotherapy drug such as doxorubicin (DOX) is widely used in chemotherapy. However, cardiotoxicity of DOX remains to be a serious clinical complication. In the current study, we aim to determine the role of PDE10A and the effect of PDE10A inhibition on cancer growth and cardiotoxicity induced by DOX.

METHODS: We used global PDE10A KO (knockout) mice and PDE10A inhibitor TP-10 to block PDE10A function. DOX-induced cardiotoxicity was evaluated in C57Bl/6J mice and nude mice with implanted ovarian cancer xenografts. Isolated adult mouse cardiomyocytes and a human ovarian cancer cell line were used for in vitro functional and mechanistic studies.

RESULTS: We found that PDE10A deficiency or inhibition alleviated DOX-induced myocardial atrophy, apoptosis, and dysfunction in C57Bl/6J mice. RNA sequencing study revealed a number of PDE10A-regulated signaling pathways involved in DOX-induced cardiotoxicity. PDE10A inhibition increased the death, decreased the proliferation, and potentiated the effect of DOX on various human cancer cells. Importantly, in nude mice with implanted ovarian cancer xenografts, PDE10A inhibition attenuated tumor growth while protecting DOX-induced cardiotoxicity. In isolated cardiomyocytes, PDE10A contributed to DOX-induced cardiomyocyte death via increasing Top2β (topoisomerase 2β) expression, mitochondrial dysfunction, and DNA damage by antagonizing cGMP/PKG (protein kinase G) signaling. PDE10A contributed to cardiomyocyte atrophy via potentiating FoxO3 (forkhead box O3) signaling via both cAMP/PKA- (protein kinase A) and cGMP/PKG-dependent signaling.

CONCLUSIONS: Taken together, our study elucidates a novel role for PDE10A in cardiotoxicity induced by DOX and cancer growth. Given that PDE10A has been already proven to be a safe drug target, PDE10A inhibition may represent a novel therapeutic strategy in cancer therapy, with effects preventing DOX-induced cardiotoxicity and simultaneously antagonizing cancer growth.

PMID:37232184 | DOI:10.1161/CIRCRESAHA.122.322264

17:27

PubMed articles on: Cardio-Oncology

Preoptimisation in patients with acute obstructive colon cancer (PREOCC) - a prospective registration study protocol

BMC Gastroenterol. 2023 May 25;23(1):186. doi: 10.1186/s12876-023-02799-z.