Background and Objectives: The standard treatment for locally advanced rectal cancer (LARC) includes neoadjuvant chemoradiotherapy (nCRT), followed by surgery with or without adjuvant chemotherapy (CT). This study evaluated the efficacy and safety of dose-escalated radiotherapy (RT) using the volumetric modulated arc therapy–simultaneous integrated boost (VMAT–SIB) technique in patients with LARC compared to 3D conformal radiotherapy (3D-CRT). Materials and Methods: This study prospectively enrolled 75 patients with LARC. All patients received nCRT using VMAT–SIB, delivering a tumor dose (TD) of 54 Gy in 25 fractions, with concomitant CT following the 5-fluorouracil and leucovorin (5-FU–LV) protocol. To compare the treatment outcomes and toxicity associated with the increased RT dose, a retrospective cohort of 62 patients treated with the 3D-CRT technique was analyzed. The 3D-CRT group received a TD of 50.4 Gy in 28 fractions with the same CT. Outcomes, including pathological complete response (pCR), tumor regression grade (TRG), and sphincter preservation rates, were compared. Results: Among operated patients, the group treated with VMAT–SIB demonstrated improved rates of pCR (20.6% vs. 8.9%), with a statistically significant trend (p = 0.06). Sphincter-preserving surgeries were performed in 49 out of 63 operated patients (77.8%) in the VMAT–SIB group, compared to 35 out of 56 (62.5%) in the 3D-CRT group. Analysis of the definitive postoperative stage revealed a significantly higher prevalence of lower T categories (T0–2) (p < 0.01), negative N status (p < 0.05), and lower stages (I + II) (p < 0.05) in patients treated with the intensified RT approach. However, no significant differences in acute toxicity were observed. Conclusions: The implementation of intensified treatment with a higher dose using the VMAT–SIB technique demonstrated significant benefits in downsizing and downstaging compared to the standard treatment approach. These findings support its integration into clinical practice. However, further prospective, multi-center studies are needed to validate these results and assess long-term outcomes.
Background/Objectives: Multidrug resistance is one the leading problems in cancer treatment, where the overexpression of P-gp and other drug efflux pumps is regarded as the primary cause. With the intention to develop transporter inhibitors, natural products such as phenolics have shown great potential and diverse attention recently. Among these, isorhamnetin (ISO), an O-methylated flavonol, is predominantly found in the fruits and leaves of various plants. Thus, this study aimed to investigate the effects of ISO on the mRNA expression of membrane transporters P-gp, BCRP, MRP 1, 2, and 5, the protein expression of P-gp, as well as the GSTP1 and GSH content in DLD1 and HCT-116 colon cancer cells. Methods: The cytotoxic effect of isorhamnetin is assessed using an MTT test, while qPCR and immunocytochemistry methods were used to determine gene and protein expression levels. The concentration of reduced glutathione was determined using the colorimetric method. Results: Based on the results, ISO can modulate the expression of transporters responsible for the resistance development (all transporters on the transcriptional level were downregulated in DLD1 cells, while only MRP1 on HCT-116 cells, and reduced P-gp protein expression on both investigated cell lines). Increased glutathione content in treated cells and GSTP1 expression suggest metabolizing the ISO and potential ejection with GSH-dependent pumps. Conclusions: Thus, in future experiments, ISO as a natural medicinal compound could be used as a chemosensitizer to prevent or overcome membrane transporter-mediated drug resistance.
Background and Objectives: The standard treatment for locally advanced rectal cancer (LARC) includes neoadjuvant chemoradiotherapy (nCRT), followed by surgery with or without adjuvant chemotherapy (CT). This study evaluated the efficacy and safety of dose-escalated radiotherapy (RT) using the volumetric modulated arc therapy-simultaneous integrated boost (VMAT-SIB) technique in patients with LARC compared to 3D conformal radiotherapy (3D-CRT). Materials and Methods: This study prospectively enrolled 75 patients with LARC. All patients received nCRT using the VMAT-SIB, delivering a tumor dose (TD) of 54 Gy in 25 fractions, with concomitant CT following the 5-fluorouracil and leucovorin (5-FU-LV) protocol. To compare the treatment outcomes and toxicity associated with the increased RT dose, a retrospective cohort of 62 patients treated with 3D-CRT techique was analyzed. The 3D-CRT group received a TD of 50.4 Gy in 28 fractions with the same CT. Outcomes, including pathological complete response (pCR), tumor regression grade (TRG), and sphincter preservation rates, were compared. Results: Among operated patients, the group treated with the VMAT-SIB demonstrated improved rates of pCR (20.6% vs. 8.9%), with a statistically significant trend (p = 0.06). Sphincter-preserving surgeries were performed in 49 out of 63 operated patients (77.8%) in VMAT-SIB group, compared to 35 out of 56 (62.5%) in 3D-CRT group. Analysis of definitive postoperative stage revealed a significantly higher prevalence of lower T categories (T0-2) (p < 0.01), negative N status (p < 0.05), and lower stages (I+II) (p < 0.05) in patients treated with intensified RT approach. However, no significant differences in acute toxicity were observed. Conclusions: The implementation of intensified treatment with a higher dose using the VMAT-SIB technique demonstrated significant benefits in downsizing and downstaging compared to the standard treatment approach. These findings support its integration into clinical practice. However, further prospective, multi-center studies are needed to validate these results and assess long-term outcomes.
Introduction. Radiation therapy after breast-conserving surgery substantially reduces the risk of local disease recurrence and moderately reduces the risk of cancer-related death. However, long-term side effects are related to numerous factors, including patient age, comorbidities, total radiation dose, fraction size, and extent of disease. Case report. We present the case of a 61-year-old female patient who developed an ulceration at the center of a postoperative scar, accompanied by progressive tissue destruction that eventually reached 6 ? 3 cm in size, resulting in rib exposure. Twenty years ago, she had a conservative surgery of the right breast due to invasive ductal carcinoma with postoperative radiation therapy to the right chest wall and the draining lymphatics. A simple mastectomy with operative removal of all sclerotic and calcified tissue, with reconstruction of the right thoracic wall, was performed by a multidisciplinary team comprising a surgical oncologist, thoracic surgeon, and plastic surgeon. The right rib cage defect of 12 ? 12 cm was reconstructed with Mersilene? mesh. A large 21 ? 15 cm island musculocutaneous latissimus dorsi flap was raised and transposed for reconstruction of the soft tissue defect. One thoracic and one wound drain were set in place. The postoperative course was uneventful, and the patient was discharged on the 12th postoperative day. She had no complications after a six-month follow-up. Conclusion. Long-term complications of radiation therapy are rare, but they are usually accompanied by severe consequences that require a multidisciplinary approach in complex surgical treatment.
Introduction: Standard therapy for patients with ovarian cancer involves cytoreductive surgery followed by platinum-based chemotherapy. Factors such as the stage of the disease at diagnosis, the histological type of the tumor, the size of the tumor and the presence of residual disease after cytoreductive surgery influence the prognosis of patients. Material and methods: This scientific paper presents a retrospective study in which the following parameters were analyzed by analyzing data obtained from the documentation of patients treated for ovarian cancer at the Institute of Oncology and Radiology of Serbia and the Institute of Oncology of Vojvodina: age of patients, period from last chemotherapy to disease progression, number of bevacizumab cycles received, disease stage, reasons for discontinuation of bevacizumab, type of surgery, and pathological verification of the disease. Results: We have shown that PFS is longer in the operated group (suboptimal operation) compared to those who were not operated (p < 0.05, Log-Rank test). There is no statistically significant difference in PFS between stages IIIc and IV, as determined by Log-Rank test. Additionally, in our research, there was no significant difference in the number of operated patients based on disease stage IIIc or IV (p = 0.361). Conclusions: Our data show that cytoreduction appears to confer a survival advantage in women with ovarian cancer treated with a combination of bevacizumab and chemotherapy. New studies should show whether the stage of the disease plays a significant role in the survival of patients with ovarian cancer.