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2021 ◽  
Vol 3 (4) ◽  
pp. 1-11
Feng Lin ◽  
Misa Anekoji ◽  
Thomas E Ichim ◽  

Heretofore, there are no FDA-approved immunotherapeutics for malignant gliomas despite many novel therapies currently in different stages of clinical trials. Malignant gliomas are immunosuppressive tumors and are difficult for immune effector cells to infiltrate the tumor sites in the central nervous system. This inefficiency results in median survival of about only two years with a few long-term survivors. Recent clinical trials of vaccine-based immunotherapies against malignant gliomas have demonstrated encouraging results in enhancing progression-free survival and overall survival of patients. The vaccine-based treatments include peptide and heat-shock proteins, dendritic cell-based vaccines, as well as viral-based immunotherapy. In this review, we will focus on recent clinical trials of neoantigen peptide vaccines on gliomas, the delivery routes of such peptide vaccines, their adjuvants, clinical challenges, and its future strategies, respectively.

2021 ◽  
Vol 11 ◽  
Alessandro Parisi ◽  
Alessio Cortellini ◽  
Olga Venditti ◽  
Roberto Filippi ◽  
Lisa Salvatore ◽  

BackgroundFew data regarding post-induction management following first-line anti-epidermal growth factor receptor (EGFR)-based doublet regimens in patients with left-sided RAS/BRAF wild-type metastatic colorectal cancer (mCRC) are available.MethodsThis multicenter, retrospective study aimed at evaluating clinicians’ attitude, and the safety and effectiveness of post-induction strategies in consecutive patients affected by left-sided RAS/BRAF wild-type mCRC treated with doublet chemotherapy plus anti-EGFR as first-line regimen, who did not experience disease progression within 6 months from induction initiation, at 21 Italian and 1 Spanish Institutions. The measured clinical outcomes were: progression-free survival (PFS), overall survival (OS), adverse events, and objective response rate (ORR).ResultsAt the data cutoff, among 686 consecutive patients with left-sided RAS/BRAF wild-type mCRC treated with doublet plus anti-EGFR as first-line regimen from March 2012 to October 2020, 355 eligible patients have been included in the present analysis. Among these, 118 (33.2%), 66 (18.6%), and 11 (3.1%) received a maintenance with 5-fluorouracil/leucovorin (5FU/LV)+anti-EGFR, anti-EGFR, and 5FU/LV, respectively, while 160 (45.1%) patients continued induction treatment (non-maintenance) until disease progression, unacceptable toxicity, patient decision, or completion of planned treatment. The median period of follow-up for the overall population was 33.7 months (95%CI = 28.9–35.6). The median PFS values of the 5FU/LV+anti-EGFR, anti-EGFR, 5FU/LV, and non-maintenance cohorts were 16.0 (95%CI = 14.3–17.7, 86 events), 13.0 (95%CI = 11.4–14.5, 56 events), 14.0 (95%CI = 8.1–20.0, 8 events), and 10.1 months (95%CI = 9.0–11.2, 136 events), respectively (p < 0.001). The median OS values were 39.6 (95%CI = 31.5–47.7, 43 events), 36.1 (95%CI = 31.6–40.7, 36 events), 39.5 (95%CI = 28.2–50.8, 4 events), and 25.1 months (95%CI = 22.6–27.6, 99 events), respectively (p < 0.001). After adjusting for key covariates, a statistically significant improvement in PFS in favor of 5FU/LV+anti-EGFR (HR = 0.59, 95%CI = 0.44–0.77, p < 0.001) and anti-EGFR (HR = 0.71, 95%CI = 0.51–0.98, p = 0.039) compared to the non-maintenance cohort was found. Compared to the non-maintenance cohort, OS was improved by 5FU/LV+anti-EGFR (HR = 0.55, 95%CI = 0.38–0.81, p = 0.002) and, with marginal significance, by anti-EGFR (HR = 0.67, 95%CI = 0.51–0.98, p = 0.051). No difference was found in ORR. Any grade non-hematological and hematological events were generally higher in the non-maintenance compared to the maintenance cohorts.ConclusionAmong the treatment strategies following an anti-EGFR-based doublet first-line induction regimen in patients affected by left-sided RAS/BRAF wild-type mCRC treated in a “real-life” setting, 5FU/LV+anti-EGFR resulted the most adopted, effective, and relatively safe regimen.

2021 ◽  
Jie-Yu Zhou ◽  
Kang-Kang Lu ◽  
Wei-Da Fu ◽  
Hao Shi ◽  
Jun-Wei Gu ◽  

Background: Triple-negative breast cancer (TNBC) is an aggressive disease. Nomograms can predict prognosis of patients with TNBC. Methods: A total of 745 eligible TNBC patients were recruited and randomly divided into training and validation groups. Endpoints were disease-free survival and overall survival. Concordance index, area under the curve and calibration curves were used to analyze the predictive accuracy and discriminative ability of nomograms. Results: Based on the training cohort, neutrophil-to-lymphocyte ratio, positive lymph nodes, tumor size and tumor-infiltrating lymphocytes were used to construct a nomogram for disease-free survival. In addition, age was added to the overall survival nomogram. Conclusion: The current study developed and validated well-calibrated nomograms for predicting disease-free survival and overall survival in patients with TNBC.

2021 ◽  
Mohammad Zuhdy ◽  
Reham Alghandour ◽  
Omar Hamdy ◽  
Islam H Metwally

Abstract Purpose: Ovarian cancer is the commonest gynecologic malignancy in Egypt. Although metastasis from ovarian cancer is common, there are still sites with rarely reported deposits as non-regional nodes, bone, and brain. Methods: This is a chorort study were we retrospectively a group of patients over 7 years period recruited from the data system of a cancer centre. All the recruited patients suffered a rare distant metastasis from ovarian cancer. Results: Nearly half of the patients already had metastasis at the time of the initial presentation, while the rest developed during the disease course. Debulking was feasible in nearly half of the patients with long overall and progression-free survival. Tumours with non-regional nodal metastases tend to have excellent survival. Conclusion: we recommend offering these patients optimal debulking and considering those with a non-regional nodal spread as having a curable disease.

2021 ◽  
chenchen Geng ◽  
Qian Pu ◽  
Shuxu Tian ◽  
Wenwen Geng ◽  
Haiyan Wang ◽  

Abstract Background: To obtain a thorough comprehension of the profile and prognosis of activating transcription factor (ATF) family members in breast cancer.Method: We searched Oncomine, GEPIA, cBioPortal, Kaplan-Meier plotter, and CancerSEA databases to assess expression level, prognostic value, and functions of ATFs in breast cancer. Results: In breast cancer, we found that the expression levels of genes like ATF1, ATF5, and ATF6, were higher than in normal tissues. While the expression levels of ATF3, ATF4, ATF7 were lower in the former than in the latter. Similarly, the ATFs protein expressions were consistent with this in the Human Protein Atlas database. High expressions of ATF2, ATF4, and ATF6-7 were associated with good relapse-free survival. Increased expressions of ATF4 and ATF7 had high overall survival. Conversely, the mRNA expression of ATF1 was negatively correlated with distant metastasis-free survival. Similarly, high expression of ATF2 had reduced post-progression survival. Conclusions: ATF1 was a target of potential therapeutic interest for breast cancer, and ATF4 and ATF6-7 were potential prognostic factors in evaluating breast cancer.

Sayali Y. Pangarkar ◽  
Akshay D. Baheti ◽  
Kunal A. Mistry ◽  
Amit J. Choudhari ◽  
Vasundhara R. Patil ◽  

Abstract Background Presence of extramural venous invasion (EMVI) is a poor prognostic factor for rectal cancer as per literature. However, India-specific data are lacking. Aim The aim of the study is to determine the prognostic significance of EMVI in locally advanced rectal cancer on baseline MRI. Materials and Methods We retrospectively reviewed 117 MRIs of operable non-metastatic locally advanced rectal cancers in a tertiary cancer institute. Three dedicated oncoradiologists determined presence or absence of EMVI, and its length and thickness, in consensus. These patients were treated as per standard institutional protocols and followed up for a median period of 37 months (range: 2–71 months). Kaplan-Meier curves (95% CI) were used to determine disease-free survival (DFS), distant-metastases free survival (DMFS), and overall survival (OS). Univariate analysis was performed by comparing groups with log-rank test. Results EMVI positive cases were 34/114 (29%). More EMVI-positive cases developed distant metastasis compared with EMVI-negative cases (14/34–41% vs. 22/83–26%). The difference, however, was not statistically significant (p = 0.146). After excluding signet-ring cell cancers (n = 14), EMVI showed significant correlation with DMFS (p = 0.046), but not with DFS or OS. The median thickness and length of EMVI was 6 and 14 mm, respectively in patients who developed distant metastasis, as compared with 5 and 11 mm in those who did not, although this difference was not statistically significant. Conclusion EMVI is a predictor of distant metastasis in locally advanced non-metastatic, non-signet ring cell rectal cancers. EMVI can be considered another high-risk feature to predict distant metastasis.

Robert L. Ferris ◽  
Yael Flamand ◽  
Gregory S. Weinstein ◽  
Shuli Li ◽  
Harry Quon ◽  

PURPOSE Definitive or postoperative chemoradiation (CRT) is curative for human papillomavirus–associated (HPV+) oropharynx cancer (OPC) but induces significant toxicity. As a deintensification strategy, we studied primary transoral surgery (TOS) and reduced postoperative radiation therapy (RT) in intermediate-risk HPV+ OPC. METHODS E3311 is a phase II randomized trial of reduced- or standard-dose postoperative RT for resected stage III-IVa (American Joint Committee on Cancer-seventh edition) HPV+ OPC, determined by pathologic parameters. Primary goals were feasibility of prospective multi-institutional study of TOS for HPV+ OPC, and oncologic efficacy (2-year progression-free survival) of TOS and adjuvant therapy in intermediate-risk patients after resection. TOS plus 50 Gy was considered promising if the lower limit of the exact 90% binomial confidence intervals exceeded 85%. Quality of life and swallowing were measured by functional assessment of cancer therapy-head and neck and MD Anderson Dysphagia Index. RESULTS Credentialed surgeons performed TOS for 495 patients. Eligible and treated patients were assigned as follows: arm A (low risk, n = 38) enrolled 11%, intermediate risk arms B (50 Gy, n = 100) or C (60 Gy, n = 108) randomly allocated 58%, and arm D (high risk, n = 113) enrolled 31%. With a median 35.2-month follow-up for 359 evaluable (eligible and treated) patients, 2-year progression-free survival Kaplan-Meier estimate is 96.9% (90% CI, 91.9 to 100) for arm A (observation), 94.9% (90% CI, 91.3 to 98.6]) for arm B (50 Gy), 96.0% (90% CI, 92.8 to 99.3) for arm C (60 Gy), and 90.7% (90% CI, 86.2 to 95.4) for arm D (66 Gy plus weekly cisplatin). Treatment arm distribution and oncologic outcome for ineligible or step 2 untreated patients (n = 136) mirrored the 359 evaluable patients. Exploratory comparison of functional assessment of cancer therapy-head and neck total scores between arms B and C is presented. CONCLUSION Primary TOS and reduced postoperative RT result in outstanding oncologic outcome and favorable functional outcomes in intermediate-risk HPV+ OPC.

Cecilia Mercado ◽  
Chloe Chhor ◽  
John R Scheel

Abstract Neoadjuvant therapy may reduce tumor burden preoperatively, allowing breast conservation treatment for tumors previously unresectable or requiring mastectomy without reducing disease-free survival. Oncologists can also use the response of the tumor to neoadjuvant chemotherapy (NAC) to identify treatment likely to be successful against any unknown potential distant metastasis. Accurate preoperative estimations of tumor size are necessary to guide appropriate treatment with minimal delays and can provide prognostic information. Clinical breast examination and mammography are inaccurate methods for measuring tumor size after NAC and can over- and underestimate residual disease. While US is commonly used to measure changes in tumor size during NAC due to its availability and low cost, MRI remains more accurate and simultaneously images the entire breast and axilla. No method is sufficiently accurate at predicting complete pathological response that would obviate the need for surgery. Diffusion-weighted MRI, MR spectroscopy, and MRI-based radiomics are emerging fields that potentially increase the predictive accuracy of tumor response to NAC.

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