The impact of radiotherapy for carcinoma of the cervix on sexual function assessed using the LENT SOMA scales.

BACKGROUND AND PURPOSE: As there are few studies examining the impact of radiotherapy on sexuality, we assessed the effect of radiotherapy for carcinoma of the cervix on sexual health and the ability of the LENT system to assess sexual function. MATERIALS AND METHODS: Using the vagina and sexual dysfunction scales of the LENT SOMA scales, subjective scores were measured prospectively before initiation of radiotherapy for 89 women, and at the following times after the start of treatment: 21, 70, 200, 400, 600 and 800 days. RESULTS: There was considerable variation in pre-radiotherapy scores that was not related to disease stage (P=0.054), but was related to patient age (P=0.037, for the average vagina scores and P=0.039 for the maximum vagina scores) The scores were influenced by prior surgery (P<0.0005 for maximum and average vagina scores, P=0.042 average and 0.017 maximum sexual dysfunction scores). For 48 patients for whom data were available at the first three time points, the vagina scores decreased significantly by 70 days compared to pre-radiotherapy scores, but not for sexual dysfunction. There was heterogeneity in the pattern of changes of scores over time: for some women there was no change in vagina subsection score, some increased, and some decreased. CONCLUSIONS: The work has shown variation both in pre-treatment sexual function and in the pattern of changes seen following radiotherapy. Our questionnaire proved useful to score subjective sexual and vaginal problems as given in the LENT subjective scales. Further study is needed to assess the effectiveness of the scales in assessing late effects.     

Effect of growth hormone replacement on bone mass in adults with adult onset growth hormone deficiency

OBJECTIVE Previous studies of the effect of GH replacement on bone mass in adults with GH deficiency have produced conflicting results. We have studied the effect of 6 and 12 months of GH replacement on bone mass in adults with adult onset GH deficiency. DESIGN Double blind placebo controlled study of GH replacement (0.125 IU/kg/week for the first month and 0.25 IU/kg/week thereafter) for 6 months and an open study for a further 6 or 12 months. PATIENTS Twenty-two adults (10 men, 12 women), aged 41.5±2.1 years (mean ± SE, range 23.6–59.5), with adult onset GH deficiency. MEASUREMENTS Single-energy quantitative computed tomography was used to measure vertebral trabecular bone mineral density (BMD), single-photon absorptiometry (SPA) was used to measure forearm cortical and integral bone mineral content and BMD and dual-energy X-ray absorptiometry (DXA) was used to measure lumbar spine, femoral neck, trochanteric and Ward's triangle Integral BMD. RESULTS After 6 months of GH replacement (n=21) there was a significant decrease In forearm cortical BMD (SPA: median change ?0.009g/cm², P=0.01), forearm Integral BMD (SPA: median change ?0.016g/cm², P=0.03), lumbar spine BMD (DXA: median change ?0.022g/cm²; P=0.003) and femoral neck BMD (DXA: median change ?0.029g/cm², P=0.006). After 12 months of GH replacement (n=13) there was a significant decrease in lumbar spine BMD (DXA: median change ?0.035 g/cm², P=0.002) from baseline. There was no significant Increase in bone mass at any site after 6 or 12 months of GH replacement. Change In bone mass was not influenced by sex of the patient or by presence or absence of additional pituitary hormone deficiencies. CONCLUSION The response of bone mass to 6 and 12 months of GH replacement in adults with adult onset GH deficiency is disappointing. Longer-term studies are required to determine whether prolonged GH replacement has a beneficial effect on bone mass.     

Parametrized rectal dose and associations with late toxicity in prostate cancer radiotherapy

Objective:

We investigated possible associations between planned dose–volume parameters and rectal late toxicity in 170 patients having radical prostate cancer radiotherapy.

Methods:

For each patient, the rectum was outlined from anorectal junction to sigmoid colon, and rectal dose was parametrized using dose–volume (DVH), dose–surface (DSH) and dose–line (DLH) histograms. Generation of DLHs differed from previous studies in that the rectal dose was parametrized without first unwrapping onto 2-dimensional dose–surface maps. Patient-reported outcomes were collected using a validated Later Effects in Normal Tissues Subjective, Objective, Management and Analytic questionnaire. Associations between dose and toxicity were assessed using a one-sided Mann–Whitney U test.

Results:

Associations (p < 0.05) were found between equieffective dose (EQD2₃) and late toxicity as follows: overall toxicity with DVH and DSH at 13–24 Gy; proctitis with DVH and DSH at 25–36 Gy and with DVH, DSH and DLH at 61–67 Gy; bowel urgency with DVH and DSH at 10–20 Gy. None of these associations met statistical significance following the application of a Bonferroni correction.

Conclusion:

Independently confirmed associations between rectal dose and late toxicity remain elusive. Future work to increase the accuracy of the knowledge of the rectal dose, either by accounting for interfraction and intrafraction rectal motion or via stabilization of the rectum during treatment, may be necessary to allow for improved dose–toxicity comparisons.

Advances in knowledge:

This study is the first to use parametrized DLHs to study associations with patient-reported toxicity for prostate radiotherapy showing that it is feasible to model rectal dose mapping in three dimensions.     

Potent Ex Vivo Activity of Naphthoquine and Methylene Blue against Drug-Resistant Clinical Isolates of Plasmodium falciparum and Plasmodium vivax

The 4-aminoquinoline naphthoquine (NQ) and the thiazine dye methylene blue (MB) have potent in vitro efficacies against Plasmodium falciparum, but susceptibility data for P. vivax are limited. The species- and stage-specific ex vivo activities of NQ and MB were assessed using a modified schizont maturation assay on clinical field isolates from Papua, Indonesia, where multidrug-resistant P. falciparum and P. vivax are prevalent. Both compounds were highly active against P. falciparum (median [range] 50% inhibitory concentration [IC₅₀]: NQ, 8.0 nM [2.6 to 71.8 nM]; and MB, 1.6 nM [0.2 to 7.0 nM]) and P. vivax (NQ, 7.8 nM [1.5 to 34.2 nM]; and MB, 1.2 nM [0.4 to 4.3 nM]). Stage-specific drug susceptibility assays revealed significantly greater IC₅₀s in parasites exposed at the trophozoite stage than at the ring stage for NQ in P. falciparum (26.5 versus 5.1 nM, P = 0.021) and P. vivax (341.6 versus 6.5 nM, P = 0.021) and for MB in P. vivax (10.1 versus 1.6 nM, P = 0.010). The excellent ex vivo activities of NQ and MB against both P. falciparum and P. vivax highlight their potential utility for the treatment of multidrug-resistant malaria in areas where both species are endemic.     

Rescheduling Part 2 of the 11+ reduces injury burden and increases compliance in semi‐professional football

Although the 11+ program has been shown to reduce injuries in sub‐elite football, program compliance is typically poor, suggesting that strategies to optimize delivery are necessary. This study investigated the effect of rescheduling Part 2 of the three‐part 11+ program on program effectiveness. Twenty‐five semi‐professional football clubs were randomly allocated to either a Standard‐11+ (n = 398 players) or P2_post group (n = 408 players). Both groups performed the 11+ program at least twice a week throughout the 2017 football season. The Standard‐11+ group performed the entire 11+ program before training activities commenced, whereas the P2_post group performed Parts 1 and 3 of the 11+ program before and Part 2 after training. Injuries, exposure, and individual player 11+ dose were monitored throughout the season. No significant between group difference in injury incidence rate (P2_post vs Standard‐11+ = 11.8 vs 12.3 injuries/1000 h) was observed. Severe time loss injuries > 28 days (33 vs 58 injuries; P < .002) and total days lost to injury (4303 vs 5815 days; P < .001) were lower in the P2_post group. A higher 11+ program dose was observed in the P2_post (29.1 doses; 95% CI 27.9‐30.1) versus Standard‐11+ group (18.9 doses; 95% CI 17.6?20.2; P < .001). In semi‐professional football, rescheduling Part 2 of the 11+ program to the end of training maintained the effectiveness of the original 11+ program to reduce injury incidence. Importantly, rescheduling Part 2 improved player compliance and reduced the number of severe injuries and total injury burden, thereby enhancing effectiveness of the 11+ program.     

Systematic comparison of plasma EBV DNA,anti-EBV antibodies and miRNA levels for early detection and prognosis of nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is originated from the epithelial cells of nasopharynx, Epstein–Barr virus (EBV)-associated and has the highest incidence and mortality rates in Southeast Asia. Late presentation is a common issue and early detection could be the key to reduce the disease burden. Sensitivity of plasma EBV DNA, an established NPC biomarker, for Stage I NPC is controversial. Most newly reported NPC biomarkers have neither been externally validated nor compared to the established ones. This causes difficulty in planning for cost-effective early detection strategies. Our study systematically evaluated six established and four new biomarkers in NPC cases, population controls and hospital controls. We showed that BamHI-W 76 bp remains the most sensitive plasma biomarker, with 96.7% (29/30), 96.7% (58/60) and 97.4% (226/232) sensitivity to detect Stage I, early stage and all NPC, respectively. Its specificity was 94.2% (113/120) against population controls and 90.4% (113/125) against hospital controls. Diagnostic accuracy of BamHI-W 121 bp and ebv-miR-BART7-3p were validated. Hsa-miR-29a-3p and hsa-miR-103a-3p were not, possibly due to lower number of advanced stage NPC cases included in this subset. Decision tree modeling suggested that combination of BamHI-W 76 bp and VCA IgA or EA IgG may increase the specificity or sensitivity to detect NPC. EBNA1 99 bp could identify NPC patients with poor prognosis in early and advanced stage NPC. Our findings provided evidence for improvement in NPC screening strategies, covering considerations of opportunistic screening, combining biomarkers to increase sensitivity or specificity and testing biomarkers from single sampled specimen to avoid logistic problems of resampling.     

Secondary effects and biochemical control in patients with early prostate cancer treated with 125-I seeds

OBJECTIVE: To retrospectively evaluate the toxicity of low-dose-rate brachytherapy and to relate it to the dose-volume to organs at risk. MATERIAL AND METHODS: We study 160 patients with early prostate cancer, treated with (125)-I implants. Most of them were T1c (63.1%), T2a (35.6%) and Gleason < or =6 (96.2%). Median PSA was 7.2 ng/ml (2.3-13.5); 85.6% were lowrisk cases and 14.4% high-risk cases. Mean follow-up was 24 months (7-48). RESULTS: Acute urinary toxicity related to urological quality of life (UQL=CVU) was tolerable in 75% and unsatisfactory in 25%. Urinary retention was present in 6.9%. IPSS, V100 and D90 were related to the urinary toxicity grade. Rectal toxicity (RTOG) G2 was 0.6%. Sexual potency showed no changes with regard to the basal in 69%. Actuarial biochemical control was 89.8% at four years. CONCLUSIONS: Brachytherapy with (125)-I seeds yields acceptable toxicity and excellent biochemical control.