Long-term outcomes of intensity-modulated radiotherapy in limited-stage small-cell lung cancer classified according to AJCC 8th tumor node metastasis staging system.

OBJECTIVE: The objective of this study was to assess treatment outcomes of intensity-modulated radiotherapy with concomitant chemotherapy and to identify prognostic factors on survival in patients with limited-stage small-cell lung cancer. PATIENTS AND METHODS: A retrospective analysis was conducted on a cohort of seventy-two patients who received curative treatment between December 2011 and January 2023. Several clinical and biochemical parameters were examined as potential prognostic factors. RESULTS: The median age was 63 years, and 79% of them were males. Concomitant chemotherapy was administered in 83% of patients. Prophylactic cranial irradiation was applied in 61% of the cohort. Two and five-year overall survival (OS), disease-free survival (DFS), and local relapse-free survival (LRFS) rates were 50% and 25%, 38% and 24%, and 44% and 25%, respectively. Univariate analysis revealed that older age, comorbid lung disease, advanced tumor-node-metastasis (TNM) stage, radiotherapy (RT) alone, and the absence of prophylactic cranial irradiation (PCI) were adverse factors affecting OS. The advanced TNM stage emerged as a significant prognostic factor for LRFS and DFS, with a notable trend toward affecting OS. CONCLUSIONS: The TNM staging system is of significance in cases classified as limited-stage small-cell lung cancer due to its prognostic implications. Our results suggest that patients with more advanced TNM stage exhibit less favorable treatment outcomes, which may require individual tailoring of new systemic therapies.

Comment on "Serum human epididymis protein 4 is associated with the treatment response of concurrent chemo-radiotherapy and prognosis in patients with locally advanced non-small cell lung cancer" by Lan WG et al

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Role of postmastectomy radiation therapy after neoadjuvant chemotherapy in locally advanced breast cancer.

Neoadjuvant chemotherapy for primary breast cancer is the gold standard in the treatment of locally advanced, inoperable breast cancer, and also based on a large body of evidence has become a standard treatment option for patients with operable disease, who are clear candidates for adjuvant chemotherapy. There are several advantages of administering neoadjuvant chemotherapy: tumor downstaging, improving the chance of breast conserving surgery, in vivo assessment of tumor sensitivity to the chosen therapeutic regimen, and early control of micro-metastatic disease. However there are substantially less data to aid in determining which patients treated with neo-adjuvant chemotherapy warrant postmastectomy radiotherapy. According to the recent literature, patients who require mastectomy after systemic therapy should receive postmastectomy radiotherapy.

Effect of ticlopidine in the prevention of radiation enteropathy.

Impairment of vascular function is considered to play an important role in chronic radiation enteropathy. In this experimental study, the role of ticlopidine, an inhibitor of ADP-induced platelet aggregation, was investigated in radiation enteropathy. 80 male Wistar albino rats, each weighing 170-200 g, were divided into four groups: (a) radiation alone (n = 20); (b) radiotherapy plus ticlopidine (n = 20); (c) ticlopidine control (n = 20) and (d) control (n = 20). Both radiation groups received 19 Gy radiation to the exteriorized intestinal segments in a single fraction. Ticlopidine or vehicle was administered 12 h after radiotherapy and continued for 1 month. Rats from every group were euthanized randomly at intervals of 6 weeks from 2 weeks to 26 weeks. Histopathological radiation injury was assessed using radiation injury scoring (RIS). Radiation with ticlopidine or radiation alone groups showed significant RIS deterioration compared with controls in all time points studied. Comparison of median RIS of radiotherapy and radiotherapy+ticlopidine groups at the 2nd, 14th and 26th weeks yielded statistically significant RIS in favour of radiotherapy+ticlopidine group (p = 0.05). However, these differences were less pronounced at the 8th and 20th week (p = 0.07). Both radiation groups had poor weight gain when compared with control and ticlopidine groups. The weight gain in radiotherapy+ticlopidine group was significantly superior to only radiation group between 10th and 20th weeks (p = 0.05). This study showed that inhibition of platelet aggregation with ticlopidine might be useful in radiation enteropathy. However, the precise role of antiaggregant therapies on radiation enteropathy should be comprehensively studied before clinical consideration.

Importance of timing of antiaggregant treatment in the prevention of radiation induced enteropathy.

Chronic radiation enteropathy (CRE) is an undesirable radiation-induced toxicity and a common health problem in patients with pelvic or abdominal malignancies. Damage to microvascular endothelial cells and connective tissue is blamed to cause this adverse effect. It is shown that platelets are the first cellular elements that initiate the homeostatic and inflammatory responses and release of several proinflammatory and fibrinogenic mediators. Antiplatelet agents such as ticlopidine and clopidogrel were shown to prevent CRE and this effect is believed to be directed by their activities against thrombocytes. However, recent studies have shown that these drugs also induce apoptosis in endothelial cells and may lead to decreased expression of endothelial prostacyclin and thrombomodulin (TM) and increased release of von Willebrand factor which are shown to be major contributors of coagulation process. Assuming that radiation induced apoptosis occur 6-10h after irradiation, we think that timing of these antiaggregant drugs with irradiation is important and a 6-10h interval between these may be beneficial to avoid this adverse interaction.

1,25-Dihydroxy vitamin D3: can it be an effective therapeutic option for aggressive fibromatosis.

Aggressive fibromatosis (AF), also known as desmoid tumor is a monoclonal fibroblastic proliferation in a collagen matrix that arises in musculoaponeurotic structures. Though considered as benign, they are locally invasive and their propensity for recurrence after conservative surgery is well documented. Addition of postoperative adjuvant radiotherapy produces higher local control rates, although recurrence rates are still high in patients with positive margins. The antineoplastic activity of vitamin D has been demonstrated both in vitro and in vivo models of several cancers. The proposed mechanisms for antineoplastic activity include inhibition of proliferation associated with cell cycle arrest, induction of apoptosis and reduction in invasiveness and angiogenesis. It has also been shown that vitamin D has a negative impact on collagen homeostasis by inhibiting the formation and increasing its degradation. Since vitamin D has an antineoplastic activity and negative effect on collagen synthesis and deposition, it is proposed that 1,25-dihydroxy vitamin D3 can be a right therapeutic option for the management of desmoid tumors.