METHODS: Adhering to the PRISMA guidelines, we systematically reviewed studies on cyclin D1-associated radioresistance in NPC from 2012 until 2023.  From our search, 15 studies were included.

RESULTS: Cyclin D1's role in radiotherapy resistance is elucidated through several mechanisms, notably SHP-1 and B-catenin. Overexpression of SHP-1 led to an increase in cyclin D1, a higher proportion of cells in the S-phase, and radioresistance.  Conversely, inhibiting β-catenin and cyclin D1 expression enhances radiation sensitivity.

MATERIALS AND METHODS: Between March 2011 and May 2012, 20 patients were treated with 55 fractions of brachytherapy using tandem and ovoids and underwent post-implant CT scans. The external beam radiotherapy (EBRT) dose was 48.6 Gy in 27 fractions. HDR brachytherapy was delivered to a dose of 21 Gy in three fractions. The ICRU bladder and rectum point doses along with 4 additional rectal points were recorded. The maximum dose (DMax) to rectum was the highest recorded dose at one of these five points. Using the HDR plus 2.6 brachytherapy treatment planning system, the bladder and rectum were retrospectively contoured on the 55 CT datasets. The DVHs for rectum and bladder were calculated and the minimum doses to the highest irradiated 2cc area of rectum and bladder were recorded (D2cc) for all individual fractions. The mean D2cc of rectum was compared to the means of ICRU rectal point and rectal DMax using the Student's t-test. The mean D2cc of bladder was compared with the mean ICRU bladder point using the same statistical test .The total dose, combining EBRT and HDR brachytherapy, were biologically normalized to the conventional 2 Gy/fraction using the linear-quadratic model. (α/β value of 10 Gy for target, 3 Gy for organs at risk).

RESULTS: The total prescribed dose was 77.5 Gy α/β10. The mean dose to the rectum was 4.58 ± 1.22 Gy for D 2cc, 3.76 ± 0.65 Gy at D ICRU and 4.75 ± 1.01 Gy at DMax. The mean rectal D 2cc dose differed significantly from the mean dose calculated at the ICRU reference point (p<0.005); the mean difference was 0.82 Gy (0.48 -1.19 Gy). The mean EQD2 was 68.52 ± 7.24 Gy α/β3 for D 2cc, 61.71 ± 2.77 Gy α/β3 at D ICRU and 69.24 ± 6.02 Gy α/β3 at DMax. The mean ratio of D 2cc rectum to D ICRU rectum was 1.25 and the mean ratio of D 2cc rectum to DMax rectum was 0.98 for all individual fractions. The mean dose to the bladder was 6.00 ± 1.90 Gy for D 2cc and 5.10 ± 2.03 Gy at D ICRU. However, the mean D 2cc dose did not differ significantly from the mean dose calculated at the ICRU reference point (p=0.307); the mean difference was 0.90 Gy (0.49-1.25 Gy). The mean EQD2 was 81.85 ± 13.03 Gy α/β3 for D 2cc and 74.11 ± 19.39 Gy α/β3 at D ICRU. The mean ratio of D 2cc bladder to D ICRU bladder was 1.24. In the majority of applications, the maximum dose point was not the ICRU point. On average, the rectum received 77% and bladder received 92% of the prescribed dose.

PATIENTS AND METHODS: Forty patients diagnosed with head and neck cancer requiring radiation to the oropharyngeal mucosal area were divided in to two groups to receive either radiation alone or radiation plus topical application of pure natural honey. Patients were treated using a 6-MV linear accelerator at a dose rate of 2 Gy per day five times a week up to a dose of 60-70 Gy. In the study arm, patients were advised to take 20 ml of pure honey 15 min before, 15 min after and 6 h post-radiation therapy. Patients were evaluated every week for the development of radiation mucositis using the Radiation Therapy Oncology Group (RTOG) grading system.

MAIN RESULTS: There was significant reduction in the symptomatic grade 3/4 mucositis among honey-treated patients compared to controls; i.e. 20% versus 75% ( p 0.00058). The compliance of honey-treated group of patients was better than controls. Fifty-five percent of patients treated with topical honey showed no change or a positive gain in body weight compared to 25% in the control arm ( p 0.053), the majority of whom lost weight.