Hypofractionated versus standard chemoradiotherapy in the definitive treatment of uterine cervix cancer: interim results of a randomized controlled clinical trial.

PURPOSE: Concurrent chemoradiation has been the mainstay of treatment for cervix cancer. We aimed to evaluate the non-inferiority of hypofractionated chemoradiation. METHODS: This study was designed as a phase 2, 1:1 randomized, investigator-blinded, controlled, non-inferiority trial and we report the interim results after 50% accrual. Cervical cancer patients with FIGO stages IIA-IIIC were recruited from April 2021 to September 2022. The intervention consisted of 40 Gy of 3D-conformal radiation therapy (RT) in 15 fractions over 3 weeks. In the control group, patients received standard chemoradiation of 45 Gy in 25 fractions over 5 weeks. Both groups received concurrent weekly cisplatin (40 mg/m2). Intravaginal brachytherapy of 28 Gy in 4 weekly fractions was delivered starting 1 week after the end of chemoradiation. The primary outcome was complete clinical response(CCR) at 3 months. Secondary outcomes included acute gastrointestinal (GI), genitourinary(GU), skin, and hematologic toxicities. A p value less than 0.05 was considered significant for analyses. RESULTS: 59 patients were randomized; 30 in the control group and 29 in the intervention group. 20/30 (66.7%) of the patients in the control group and 19/29 (65.5%) in the intervention group achieved a CCR (absolute difference of 0.011, 95% CI - 0.23 to 0.25, p value: 0.13). There was a significantly higher rate of acute grade ≥ 3 GI toxicity in the intervention group (27.6%) compared with the control group (6.7%) (p value 0.032). CONCLUSIONS: Despite an absolute difference of 1.1% in the 3-month CCR, our interim analysis failed to show the non-inferiority of the hypofractionated chemoradiation. Due to the higher GI toxicities, we will continue this trial using intensity-modulated radiation therapy. REGISTRATION NUMBER AND DATE: ClinicalTrials.gov: NCT04831437, 2021.4.1.

Clinical Effects of Immuno-Oncology Therapy on Glioblastoma Patients: A Systematic Review.

The most prevalent and deadly primary malignant glioma in adults is glioblastoma (GBM), which has a median survival time of about 15 months. Despite the standard of care for glioblastoma, which includes gross total resection, high-dose radiation, and temozolomide chemotherapy, this tumor is still one of the most aggressive and difficult to treat. So, it is critical to find more potent therapies that can help glioblastoma patients have better clinical outcomes. Additionally, the prognosis for recurring malignant gliomas is poor, necessitating the need for innovative therapeutics. Immunotherapy is a rather new treatment for glioblastoma and its effects are not well studied when it is combined with standard chemoradiation therapy. We conducted this study to evaluate different glioblastoma immunotherapy approaches in terms of feasibility, efficacy, and safety. We conducted a computer-assisted literature search of electronic databases for essays that are unique, involve either prospective or retrospective research, and are entirely written and published in English. We examined both observational data and randomized clinical trials. Eighteen studies met the criteria for inclusion. In conclusion, combining immunotherapy with radiochemotherapy and tumor removal is generally possible and safe, and rather effective in the prolongation of survival measures.

State of the Art in Combination Immuno/Radiotherapy for Brain Metastases: Systematic Review and Meta-Analysis.

OBJECTIVES: Common origins for brain metastases (BMs) are melanoma, lung, breast, and renal cell cancers. BMs account for a large share of morbidity and mortality caused by these cancers. The advent of new immunotherapeutic treatments has made a revolution in the treatment of cancer patients and particularly, as a new concept, if it is combined with radiotherapy, may lead to considerably longer survival. This systematic review and meta-analysis aimed to evaluate the survival rate and toxicities of such a combination in brain metastases. METHODS: To perform a systematic review of the literature until January 2021 using electronic databases such as PubMed, Cochrane Library, and Embase; the Newcastle-Ottawa Scale was used to evaluate the quality of cohort studies. For data extraction, two reviewers extracted the data blindly and independently. Hazard ratio with 95% confidence interval (CI), fixed-effect model, and inverse-variance method was calculated. The meta-analysis has been evaluated with the statistical software Stata/MP v.16 (The fastest version of Stata). RESULTS: In the first step, 494 studies were selected to review the abstracts, in the second step, the full texts of 86 studies were reviewed. Finally, 28 studies were selected consisting of 1465 patients. The addition of IT to RT in the treatment of brain metastasis from melanoma and non-small-cell lung carcinoma was associated with a 39% reduction in mortality rate and has prolonged overall survival, with an acceptable toxicity profile. The addition of IT to RT compared with RT alone has a hazard ratio of 0.39(95% CI 0.34-0.44). CONCLUSIONS: A combination of immuno/radiotherapy (IR) for the treatment of patients with BMs from melanoma and non-small-cell lung carcinoma has prolonged overall survival and reduced mortality rate, with acceptable toxicity. In terms of timing, RT seems to have the best effect on the result when performed before or simultaneously with immunotherapy.

Delayed Effect of Dendritic Cells Vaccination on Survival in Glioblastoma: A Systematic Review and Meta-Analysis.

BACKGROUND: Dendritic cell vaccination (DCV) strategies, thanks to a complex immune response, may flare tumor regression and improve patients' long-term survival. This meta-analysis aims to assess the efficacy of DCV for newly diagnosed glioblastoma patients in clinical trials. METHODS: The study databases, including PubMed, Web of Knowledge, Google Scholar, Scopus, and Cochrane, were searched by two blinded investigators considering eligible studies based on the following keywords: "glioblastoma multiforme", "dendritic cell", "vaccination", "immunotherapy", "immune system", "immune response", "chemotherapy", "recurrence", and "temozolomide". Among the 157 screened, only 15 articles were eligible for the final analysis. RESULTS: Regimens including DCV showed no effect on 6-month progression-free survival (PFS, HR = 1.385, 95% CI: 0.822-2.335, p = 0.673) or on 6-month overall survival (OS, HR = 1.408, 95% CI: 0.882-2.248, p = 0.754). In contrast, DCV led to significantly longer 1-year OS (HR = 1.936, 95% CI: 1.396-2.85, p = 0.001) and longer 2-year OS (HR = 3.670, 95% CI: 2.291-5.879, p = 0.001) versus control groups. Hence, introducing DCV could lead to increased 1 and 2-year survival of patients by 1.9 and 3.6 times, respectively. CONCLUSION: Antitumor regimens including DCV can effectively improve mid-term survival in patients suffering glioblastoma multiforme (GBM), but its impact emerges only after one year from vaccination. These data indicate the need for more time to achieve an anti-GBM immune response and suggest additional therapeutics, such as checkpoint inhibitors, to empower an earlier DCV action in patients affected by a very poor prognosis.

Durable complete response to pembrolizumab in microsatellite stable colorectal cancer.

INTRODUCTION: Immunotherapy by checkpoint inhibitors, i.e., anti-programmed death-1(PD-1) or anti-programmed death-ligand 1 (PD-L1) antibodies, has gained more attention managing solid tumors. Pembrolizumab (an anti-PD-1 antibody) in metastatic colorectal cancer (CRC) was approved in 2017 by the US FDA. REASON FOR THE REPORT: Pembrolizumab is not effective in microsatellite stable, mismatch-repair-proficient (MSS-pMMR) molecular phenotype, which comprises most CRC patients. In this report, we present the first case of metastatic CRC with a dramatic and durable response to pembrolizumab despite being of MSS-pMMR phenotype. A 34-year-old woman, presented seven years ago with T3N2bM0 colon cancer and an appendix carcinoid tumor. The last relapse with bilateral pulmonary metastases was refractory to all treatments. Although it seemed unresponsive to immunotherapy because of MSS molecular phenotype, due to the high expression level of PD-L1 (85%), we started treatment with pembrolizumab 200 mg every three weeks and continued for the overall 19 courses. Surprisingly, a rapid and complete response was observed that last until now, i.e., 17 months after discontinuation of pembrolizumab. OUTCOME: Despite non-promising results in the current clinical trials, MSS-pMMR colorectal cancer patients' deprivation from immunotherapy seems not to be reasonable. There are ongoing clinical trials on checkpoint inhibitors either alone or in combination with other drugs. However, immunostaining for PD-L1 should be considered as a possible response predictor. Immunotherapy either by cell-based approaches or by checkpoint inhibitors may revolutionize cancer treatment Pembrolizumab has been approved by the FDA in 2017 for colorectal cancer. However, MSS-pMMR molecular phenotype which comprises the majority of CRC patients, has not shown a good response to checkpoint inhibitors. We present a MSS-pMMR case with complete and durable response to pembrolizumab We suggest immunostaining for PD-L1 as a possible response predictor to checkpoint inhibitors.

Adjunctive treatment of myxopapillary ependymoma.

Myxopapillary ependymoma are rare tumors and optimal therapeutic strategy is remained controversial. The main treatments for myxopapillary ependymoma tumors include surgery and radiotherapy. Hence, the present study aimed to review adjuvant treatment of myxopapillary ependymoma, focusing on spinal myxopapillary ependymoma. The information sources of all articles were the English authoritative databases including PubMed, Web of science, Scopus, Science direct and Google scholar. In this review study, the keywords including adjuvant, treatment, myxopapillary and ependymoma were selected from MeSH medical library. Related articles were published from 2000 to 2020. Given radiation tolerance in the spinal cord is 10-15% lower than that of the brain, it also should be noted that with increased dose and scope of therapeutic field, the corresponding risks are increased, as well. Also, chemotherapy has never been used as the primary treatment approach. Radiotherapy's value is considered while involving with sensitive areas where chemotherapy is also recommended. Gross total resection is the preferred primary treatment. But the role of adjuvant radiotherapy is debated in different tumor and patient scenarios and no standard treatment strategy had been defined yet. The bottom line is that as long as cellular and molecular methods or gene therapy can be used in the treatment of myxopapillary ependymoma, all the studies confirm that the best treatment method is still wide surgical resection as much as possible.

High-dose-rate brachytherapy in treatment of non-melanoma skin cancer of head and neck region: preliminary results of a prospective single institution study.

PURPOSE: Skin cancers are the most common human malignancy with increasing incidence. Currently, surgery is standard of care treatment for non-melanoma skin cancers. However, brachytherapy is a growing modality in the management of skin cancers. Therefore, we aimed to assess the outcome of patients with non-melanoma skin cancers treated by high-dose-rate (HDR) brachytherapy with surface mold technique. MATERIAL AND METHODS: In this prospective study, we recruited patients with basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) of the skin who were candidates for definitive or adjuvant brachytherapy during 2013-2014. Alginate was used for making the individualized surface molds for each patient. Patients were treated with afterloading radionuclide HDR brachytherapy machine, with a total dose of 30-52 Gy in 10-13 fractions. Participants were followed for 2 years for radiation toxicity, cosmetic results, and local failures. RESULTS: A total of 60 patients (66.7% male; median age, 71 years) were included, of which 42 (70.0%) underwent definitive radiotherapy. Seventy-five percent of lesions were BCC. The mean total dose was 39.6 ± 5.4 Gy. Of patients in definitive group, 40/42 (95.2%) experienced complete clinical response after 3 months. The recurrence rate was 2/18 (11.11%) and 1/42 (2.38%) in adjuvant and definitive groups, respectively. The percentage of grade 3-4 acute (3-month post-treatment) and late toxicities (2 years post-treatment) was 6.7% and 0%, respectively. The cosmetic results were good/excellent in 96.2% of patients after 2 years of follow-up. CONCLUSIONS: With appropriate patient selection and choosing as lowest dose per fraction as possible, HDR brachytherapy with customized surface molds yields good oncological and cosmetic results for the treatment of localized skin BCC and SCC.