Comparison of preoperative chemoradiation with radiation or chemotherapy alone in patients with non-metastatic, resectable retroperitoneal sarcoma

Aim: Optimal preoperative therapy regimen in the treatment of resectable retroperitoneal sarcoma (RPS) remains unclear. This study compares the impact of preoperative radiation, chemoradiation and chemotherapy on overall survival (OS) in RPS patients. Materials and Methods: The National Cancer Database (NCDB) was queried for patients with non-metastatic, resectable RPS (2006–15). The primary endpoint was OS, evaluated by Kaplan–Meier method, log-rank test, Cox multivariable analysis and propensity score matching. Results: A total of 1,253 patients met the inclusion criteria, with 210 patients (17%) receiving chemoradiation, 850 patients (68%) receiving radiation and 193 patients (15%) receiving chemotherapy. On Cox multivariable analysis, when compared to preoperative chemoradiation, preoperative radiation was not associated with improved OS (hazards ratio [HR] 0·98, 95% CI 0·76–1·25, p = 0·84), while preoperative chemotherapy was associated with worse OS (HR 1·64, 95% CI 1·24–2·18, p < 0·001). Similar findings were observed in 199 and 128 matched pairs for preoperative radiation and chemotherapy, respectively, when compared to preoperative chemoradiation. Findings: Our study suggested an OS benefit in using preoperative chemoradiation compared to chemotherapy alone, but OS outcomes were comparable between preoperative chemoradiation and radiation alone.

Radiological progression of extremity soft tissue sarcoma following preoperative radiotherapy predicts for poor survival

Objectives: To determine if radiological response to preoperative radiotherapy is related to oncologic outcome in patients with extremity soft tissue sarcomas (STS). Methods: 309 patients with extremity STS who underwent preoperative radiation and wide resection were identified from a prospective database. Pre-and post-radiation MRI scans were retrospectively reviewed. Radiological response was defined by the modified Response Evaluation Criteria in Solid Tumours (RECIST).Local recurrence-free (LRFS), metastasis-free (MFS) and overall survival (OS) were compared across response groups. Results: Tumour volume decreased in 106 patients (34.3%; PR- Partial Responders), remained stable in 97 (31.4%; SD- Stable Disease), increased in 106 (34.3%; PD- Progressive Disease). The PD group were older (p = 0.007), had more upper extremity (p = 0.03) and high grade tumours (p < 0.001). 81% of myxoid liposarcomas showed substantial decrease in size. There was no difference in initial tumour diameter (p = 0.5), type of surgery (p = 0.5), margin status (p = 0.4), or complications (p = 0.8) between the three groups. There were ten (3.2%) local recurrences with no differences between the three response groups (p = 0.06). Five-year MFS was 52.1% for the PD group versus 73.8 and 78.5% for the PR and SD groups respectively (p < 0.001). OS was similar (p < 0.001). Following multivariable analysis, worse MFS and OS were associated with higher grade, larger tumour size at diagnosis and tumour growth following preoperative radiation. Older age was also associated with worse OS. Conclusion: STS that enlarge according to RECIST criteria following preoperative radiotherapy identify a high risk group of patients with worse systemic outcomes but equivalent local control. Advances in knowledge: Post radiation therapy, STS enlargement may identify patients with potential for worse systemic outcomes but equivalent local control. Therefore, adjunct therapeutic approaches could be considered in these patients.

Evaluating Thresholds to Adopt Hypofractionated Preoperative Radiotherapy as Standard of Care in Sarcoma

Introduction. Data supporting hypofractionated preoperative radiation therapy (RT) for patients with extremity and trunk soft tissue sarcoma (STS) are currently limited to phase II single-institution studies. We sought to understand the type and thresholds of clinical evidence required for experts to adopt hypofractionated RT as a standard-of-care option for patients with STS. Methods. An electronic survey was distributed to multidisciplinary sarcoma experts. The survey queried whether data from a theoretical, multi-institutional, phase II study of 5-fraction preoperative RT could change practice. Using endpoints from RTOG 0630 as a reference, the survey also queried thresholds for acceptable local control, wound complication, and late toxicity for the study protocol to be accepted as a standard-of-care option. Responses were logged from 8/27/2020 to 9/8/2020 and summarized graphically. Results. The survey response rate was 55.3% (47/85). Local control is the most important clinical outcome for sarcoma specialists when evaluating whether an RT regimen should be considered standard of care. 17% (8/47) of providers require randomized phase III evidence to consider hypofractionated preoperative RT as a standard-of-care option, whereas 10.6% (5/47) of providers already view this as a standard-of-care option. Of providers willing to change practice based on phase II data, most (78%, 29/37) would accept local control rates equivalent to or less than those in RTOG 0630, as long as the rate was higher than 85%. However, 51.3% (19/37) would require wound complication rates superior to those reported in RTOG 0630, and 46% (17/37) of respondents would accept late toxicity rates inferior to RTOG 0630. Conclusion. Consensus building is needed among clinicians regarding the type and threshold of evidence needed to evaluate hypofractionated RT as a standard-of-care option. A collaborative consortium-based approach may be the most pragmatic means for developing consensus protocols and pooling data to gradually introduce hypofractionated preoperative RT into routine practice.

Recent Progress in the Neoadjuvant Treatment Strategy for Locally Advanced Esophageal Cancer

Neoadjuvant therapies, primarily chemotherapy and chemoradiotherapy, are able to improve the overall survival (OS) in patients with locally advanced resectable esophageal cancer (EC) based on the results of several randomized clinical trials. The advantage of neoadjuvant therapy is chiefly attributed to the decreased risk of local–regional recurrence and distant metastasis. Thus, it has been recommended as standard treatment for patients with resectable EC. However, several fundamental problems remain. First, the combination of neoadjuvant chemotherapy (nCT), neoadjuvant chemoradiotherapy (nCRT), and surgery for EC patients with different histological types remains controversial. Furthermore, to reduce the toxicity of preoperative chemotherapy and the risk of complications caused by preoperative radiation therapy, the treatment protocols of nCT and nCRT still need to be investigated and optimized by prospective trials. Moreover, for patients with complete clinical response following neoadjuvant therapy, it is worth ascertaining whether a “watch and wait” surveillance plus surgery-as-needed policy is more favorable, as well as, in addition to preoperative chemoradiotherapy, whether immunotherapy, especially when combined with the traditional neoadjuvant therapy regimens, brings new prospects for EC treatment. In this review, we summarize the recent insights into the research progress and existing problems of neoadjuvant therapy for locally advanced resectable EC.

Orocutaneous Fistula After Oral Cavity Resection and Reconstruction: Systematic Review and Meta-Analysis

Objective: Orocutaneous fistula (OCF) after reconstruction for oral cavity resection can lead to prolonged hospitalization and adjuvant treatment delay. Few studies have examined factors leading to OCF after oral cavity resection. Primary objective: evaluate overall incidence and factors associated with OCF after oral cavity reconstruction. Data Sources: Scopus 1960—database was searched for terms: “orocutaneous fistula,” “oro cutaneous fistula,” “oral cutaneous fistula,” “orocervical fistula,” “oral cavity salivary fistula.” Review Methods: English language studies with >5 patients undergoing reconstruction after oral cavity cancer resection were included. About 1057 records initially screened; 214 full texts assessed; 78 full-texts included. PRISMA guidelines were followed, and MINORS criteria used to assess risk of bias. Data were pooled using random-effects model. Primary outcome was OCF incidence. Meta-analysis to determine the effect of preoperative radiation on OCF conducted on 12 eligible studies. Pre-collection hypothesis was that prior radiation therapy is associated with increased OCF incidence. Post-collection analyses: free versus pedicled flaps; mandible-sparing versus segmental mandibulectomy. Results: Seventy-eight studies were included in meta-analysis of overall OCF incidence. Pooled effect size showed overall incidence of OCF to be 7.71% (95% CI, 6.28%-9.13%) among 5400 patients. Meta-analysis of preoperative radiation therapy on OCF showed a pooled odds ratio of 1.68 (95% CI, 0.93-3.06). OCF incidence was similar between patients undergoing free versus pedicled reconstruction, or segmental mandibulectomy versus mandible-sparing resection. Conclusion: Orocutaneous fistula after oral cavity resection has significant incidence and clinical impact. Risk of OCF persists despite advances in reconstructive options; there is a trend toward higher risk after prior radiation.

Novel Strategies for Nanoparticle-Based Radiosensitization in Glioblastoma

Radiotherapy (RT) is one of the cornerstones in the current treatment paradigm for glioblastoma (GBM). However, little has changed in the management of GBM since the establishment of the current protocol in 2005, and the prognosis remains grim. Radioresistance is one of the hallmarks for treatment failure, and different therapeutic strategies are aimed at overcoming it. Among these strategies, nanomedicine has advantages over conventional tumor therapeutics, including improvements in drug delivery and enhanced antitumor properties. Radiosensitizing strategies using nanoparticles (NP) are actively under study and hold promise to improve the treatment response. We aim to describe the basis of nanomedicine for GBM treatment, current evidence in radiosensitization efforts using nanoparticles, and novel strategies, such as preoperative radiation, that could be synergized with nanoradiosensitizers.

Postradiation Regression of Locally Advanced Rectal Cancer: Two Clinical Cases

In the Russian Federation, the incidence of malignant neoplasms is more than 50 thousand new cases per year. Since 1990 the combined treatment method is the standard in the treatment of patients with locally advanced rectal cancer. During the evolution of this method, preoperative radiation / chemo-radiation therapy has taken a strong position in the standards for treatment of rectal cancer. Currently, preoperative remote radiation therapy at a dose of 45-52Gy is included in treatment standards for rectal cancer. The main objective of neoadjuvant treatment is to achieve tumor regression. When a complete regression of the tumor is achieved, the task of choosing tactics arises - to carry out surgical treatment, or to apply expectant tactics. In the first clinical case, the patient underwent preoperative chemoradiation treatment with 40.8 Gy combined with capecitabine, after which 4 courses of consolidating chemotherapy were carried out followed by surgery. In the second case, the patient underwent neoadjuvant chemoradiation therapy with 52.5 Gy combined with capecitabine. Given the pronounced positive dynamics, 4 courses of consolidating chemotherapy were performed. After the control study, a complete tumor response to the therapy was revealed. Considering the MRI data and the pronounced positive dynamics, the decision of the multidisciplinary team was the tactics of dynamic observation of the patient.