Neo-adjuvant platinum-based chemotherapy followed by chemoradiation and radical surgery in locally advanced cervical cancer (Lacc) patients: A phase II study

Ferrandina, Gabriella; Palluzzi, Eleonora; Gallotta, Valerio; Gambacorta, Maria Antonietta; Autorino, Riccardo; Turco, Luigi Carlo; Macchia, G.; Cosentino, Francesco; Gui, Benedetta; Mattoli, Maria Vittoria; Ronzino, Graziana; Valentini, Vincenzo

doi:10.1016/j.ejso.2018.04.019

Cited by 31 publications

(22 citation statements)

References 26 publications

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“…This not only benefits young patients in preserving ovarian function and sexual capacity but also improves survival outcome. Recently, NACT has been explored as an approach to fasten the initiation of treatment before access to radiation in some countries with insufficient radiation equipment (35). Radiomic model may assist in identifying qualified patients to undergo NACT before radiation.…”

Section: Discussionmentioning

confidence: 99%

Prediction of Response to Preoperative Neoadjuvant Chemotherapy in Locally Advanced Cervical Cancer Using Multicenter CT-Based Radiomic Analysis

et al. 2020

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Objective: To investigate whether pre-treatment CT-derived radiomic features could be applied for prediction of clinical response to neoadjuvant chemotherapy (NACT) in locally advanced cervical cancer (LACC).Patients and Methods: Two hundred and seventy-seven LACC patients treated with NACT followed by surgery/radiotherapy were included in this multi-institution retrospective study. One thousand and ninety-four radiomic features were extracted from venous contrast enhanced and non-enhanced CT imaging for each patient. Five combined methods of feature selection were used to reduce dimension of features. Radiomics signature was constructed by Random Forest (RF) method in a primary cohort of 221 patients. A combined model incorporating radiomics signature with clinical factors was developed using multivariable logistic regression. Prediction performance was then tested in a validation cohort of 56 patients.Results: Radiomics signature containing pre-and post-contrast imaging features can adequately distinguish chemotherapeutic responders from non-responders in both primary and validation cohorts [AUCs: 0.773 (95% CI, 0.701-0.845) and 0.816 (95% CI, 0.690-0.942), respectively] and remain relatively stable across centers. The combined model has a better predictive performance with an AUC of 0.803 (95% CI, 0.734-0.872) in the primary set and an AUC of 0.821 (95% CI, 0.697-0.946) in the validation set, compared to radiomics signature alone. Both models showed good discrimination, calibration.Conclusion: Newly developed radiomic model provided an easy-to-use predictor of chemotherapeutic response with improved predictive ability, which might facilitate optimal treatment strategies tailored for individual LACC patients.

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Section: Discussionmentioning

confidence: 99%

Prediction of Response to Preoperative Neoadjuvant Chemotherapy in Locally Advanced Cervical Cancer Using Multicenter CT-Based Radiomic Analysis

et al. 2020

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“…Surgery and radiotherapy supplemented by chemotherapy are standard treatments for early-stage disease. More advanced cervical cancer is treated mainly by concurrent radiotherapy and chemotherapy [28,29]. Cervical cancer is radiosensitive, but radiotherapy resistance has been reported in both cervical cancer cells and clinical practice.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Uncoupling Protein 2 Enhances the Radiosensitivity of Cervical Cancer Cells by Promoting the Production of Reactive Oxygen Species

Liu

Huang

Dong

et al. 2020

Oxidative Medicine and Cellular Longevity

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Objective. The mechanism of enhanced radiosensitivity induced by mitochondrial uncoupling protein UCP2 was investigated in HeLa cells to provide a theoretical basis as a novel target for cervical cancer treatment. Methods. HeLa cells were irradiated with 4 Gy X-radiation at 1.0 Gy/min. The expression of UCP2 mRNA and protein was assayed by real-time quantitative polymerase chain reaction and western blotting. UCP2 siRNA and negative control siRNA fragments were constructed and transfected into HeLa cells 24 h after irradiation. The effect of UCP2 silencing and irradiation on HeLa cells was determined by colony formation, CCK-8 cell viability, γH2AX immunofluorescence assay of DNA damage, Annexin V-FITC/PI apoptosis assay, and propidium iodide cell cycle assay. The effects on mitochondrial structure and function were investigated with fluorescent probes including dichlorodihydrofluorescein diacetate (DCFH-DA) assay of reactive oxygen species (ROS), rhodamine 123, and MitoTracker Green assay of mitochondrial structure and function. Results. Irradiation upregulated UCP2 expression, and UCP2 knockdown decreased the survival of irradiated HeLa cells. UCP2 silencing sensitized HeLa cells to irradiation-induced DNA damage and led to increased apoptosis, cell cycle arrest in G2/M, and increased mitochondrial ROS. Increased radiosensitivity was associated with an activation of P53, decreased Bcl-2, Bcl-xl, cyclin B, CDC2, Ku70, and Rad51 expression, and increased Apaf-1, cytochrome c, caspase-3, and caspase-9 expression. Conclusions. UCP2 inhibition augmented the radiosensitivity of cervical cancer cells, and it may be a potential target of radiotherapy of advanced cervical cancer.

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“…Recently, clinical management for advanced cervical cancer has also included targeted therapy, intensitymodulated radiotherapy, dose-dense chemotherapy and minimally invasive surgery [15][16][17]. However, despite the advances in chemotherapy and radiotherapy, random- ized trials have not demonstrated their superiority over surgery and chemotherapy [18]; thus, if indicated, the role of surgery for stage IVA cervical carcinoma should be considered a viable option in patients for whom the tumor is amenable to surgical resection [13,14].…”

Section: Discussionmentioning

confidence: 99%

Neoadjuvant chemotherapy, radical hysterectomy and chemoradiation for stage iva cervical carcinoma

2020

European Journal of Gynaecological Oncology

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Despite the efficacy of chemotherapy and radiotherapy in the management of locally advanced cervical carcinoma, the overall survival rates are relatively inauspicious. We recount a case involving a 56-year-old stage IVA cervical cancer patient who underwent neoadjuvant chemotherapy, a type V radical hysterectomy and adjuvant chemoradiation in April 2006. The patient remained in clinical remission for five years until she developed a metastatic pulmonary nodule in her right middle lobe that originated from the primary cervical cancer. Thereafter, the patient was diagnosed with a right metastatic cardiophrenic nodule that responded favorably to chemotherapy. However, in August 2014, she presented with a metastatic posterior cranial fossa tumor from which she ultimately expired; interestingly, radiologic imaging revealed no evidence of an abdominopelvic recurrence. While a radical hysterectomy is often indicated for advanced cervical cancer patients with residual disease or those who fail chemoradiation, perhaps in select cases (e.g., stage IVA disease), initial treatment with neoadjuvant chemotherapy and surgery followed by chemoradiation may improve patient survival.

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Neo-adjuvant platinum-based chemotherapy followed by chemoradiation and radical surgery in locally advanced cervical cancer (Lacc) patients: A phase II study

Cited by 31 publications

References 26 publications

Prediction of Response to Preoperative Neoadjuvant Chemotherapy in Locally Advanced Cervical Cancer Using Multicenter CT-Based Radiomic Analysis

Prediction of Response to Preoperative Neoadjuvant Chemotherapy in Locally Advanced Cervical Cancer Using Multicenter CT-Based Radiomic Analysis

Inhibition of Uncoupling Protein 2 Enhances the Radiosensitivity of Cervical Cancer Cells by Promoting the Production of Reactive Oxygen Species

Neoadjuvant chemotherapy, radical hysterectomy and chemoradiation for stage iva cervical carcinoma

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