Efficacy and Safety of Two Neoadjuvant Strategies With Bevacizumab in MRI-Defined Locally Advanced T3 Resectable Rectal Cancer: Final Results of a Randomized,Noncomparative Phase 2 INOVA Study

BackgroundRecurrence and distant metastases remain a significant issue in locally advanced rectal cancer (LARC). Several multimodal strategies are assessed in clinical trials.Patients and MethodsPatients with mid/low magnetic resonance imaging–defined high-risk LARC were randomized to arm A (12-week bevacizumab + FOLFOX-4 then bevacizumab–5-fluorouracil [5-FU]–radiotherapy [RT] before total mesorectal excision [TME]) or arm B (bevacizumab-5-FU–RT then TME). Long-term efficacy and safety up to 5 years’ follow-up are reported. No comparison between arms was planned.ResultsOverall, 91 patients (46 in arm A and 45 in arm B) were included. Main results have been presented previously. During the late follow-up period (> 4 weeks after surgery), 4 patients (8.7%) in arm A and 4 (8.9%) in arm B experienced grade 3/4 adverse events related to bevacizumab; the most frequent were 2 anastomotic fistulas (both in arm A) and abscesses (1 in arm A and 2 in arm B). At 5 years’ follow-up, 9 (19.6%) and 11 (24.4%) patients in arms A and B developed a fistula in the year after surgery, and 2 (4.3%) in arm A at > 1 year after surgery. Most resolved before study end. Five-year disease-free survival was 70% and 64.3% in arms A and B, respectively. Five-year overall survival was 90.5% (95% confidence interval, 76.7, 96.3) in arm A and 72.7% (95% confidence interval, 56.0, 83.9) in arm B.ConclusionNeoadjuvant bevacizumab + FOLFOX-4 may have the potential to increase survival outcomes when followed by bevacizumab–5-FU–RT and TME in LARC. Bevacizumab–5-FU–RT then TME was associated with a higher-than-projected rate of anastomotic fistulas. Further research of neoadjuvant strategies in LARC is encouraged.     

Quality of weight loss during chemoradioherapy in patients with nasopharyngeal cancers

PurposeRadiation therapy with chemotherapy (CCR) is currently the gold standard treatment for nasopharyngeal carcinoma (NPC). Anatomical changes are mainly due to weight loss. Our prospective study aimed to evaluate the nutritional status and the quality of weight loss in our patients to adapt the subsequent nutritional management of patients during treatment for NPC.Patients and methodsA prospective, single-center study of 27 patients with non-metastatic NPC treated in our oncology radiotherapy department between August 2020 and March 2021. Data from interrogation, physical examination, and bioelectrical impedancemetry (weight [W], body mass index [BMI], fat index [GI], fat mass [FM], and fat-free mass (FFM]) were collected at the beginning, the mid, and the end of treatment.ResultsWeight loss from mid to end of treatment (median = −4 kg [−9.4; −0.9]) was greater than that from baseline to mid-treatment (median = −2.9 kg [−8.8; 1.8]) (P = 0.016). Weight loss during the entire treatment was −6.2 kg [−15.6; −2.5] (8.4%). The losses of FM were identical between the beginning-mid treatment and the mid-end treatment; they were respectively −1.4 kg [−8.5; 4.2] and −1.4 kg [−8.2; 7.8] (P = 0.4). FFM losses between the mid- and the end of treatment (−2.5 kg [−27.8; 0.5]) were greater than those between baseline and mid-treatment (−1.1 kg [−7.1; 4.7]) (P = 0.014). Median FFM loss during treatment was −3.6 kg [−28.1; 2.6]).ConclusionThe results of our study show that weight loss during CCR for NPC is complex and is not just about loss but about a disruption of body composition. Regular follow-ups by nutritionists are required to prevent denutrition during treatment.     

恶性胶质瘤cyclinD1及p16表达与预后相关性研究

目的 探讨恶性胶质瘤细胞周期蛋白D1(cyclinD1)和p16蛋白表达与手术及放射治疗后肿瘤复发的相关关系。方法 在我院行手术全切及正规放射治疗的恶性胶质瘤患中，已证实复发62例，肿瘤标本检测cyclinD1和p16蛋白的表达情况，结合传统预后因素(性别、年龄、病程、肿瘤大小、肿瘤性质)采用Kaplan—Meier方法并用logrank检验对肿瘤复发进行单因素分析，多因素分析采用COX逐步回归模型。结果 病程、肿瘤大小、肿瘤性质和cyclinD1及p16蛋白表达情况均可作为恶性胶质瘤手术及放射治疗后复发的独立预测因素，多因素分析显示p16蛋白表达和肿瘤病理性质对肿瘤复发的预测作用较强。结论 肿瘤细胞cyclinD1和p16蛋白表达可能与手术及放射治疗后复发的时间长短有关。     

放射治疗中热塑体膜对皮肤剂量的影响

目的研究热塑体膜在6MV和16MV光子束治疗肿瘤时对皮肤剂量的影响。方法使用瓦里安2300CD直线加速器,PTW3381平行板电离室。测量条件：200MU,10cm×10cm照射野,100cm源皮距。在有热塑体膜和无热塑体膜的情况下,分别测量模体表面、模体下1、2、3mm处的剂量,分别比较不同条件下相同深度的剂量。结果放置热塑体膜后模体表面的吸收剂量明显高于无热塑体膜时的吸收剂量,6MV光子束时表面增加了36.2%,16MV光子束时表面增加了47.7%（P〈0.01）,模体表面以下1、2、3mm的剂量同样明显增加,但增加的幅度随深度的增加而逐渐减少。结论使用热塑体膜能显著增加皮肤表面剂量,放疗医师在做放疗计划设计时,应考虑到热塑膜对患者皮肤剂量的影响及其生物效应,尽量采用各种措施减少放射性皮肤损伤。     

Economic study of neutropenia induced by myelotoxic chemotherapy

This article describes the economic and social impact of nutropenia induced by myelotoxic chemotherapy in patients with cancer during the period 1 January–31 December 1991. Neutropenia is a life-threatening complication of chemotherapy in patients with cancer. The episodes of (ever and infections originating from neutropenia require hospitalization of the patient until the granulocyte levels are restored. The calculation of the economic cost was based on the following parameters: length of stay in hospital, analytical tests performed on the patient, type and cost of drug therapy administered, blood transfusions performed, health assistance received, cost of isolation and absence from work. The overall economic cost of neutropenia in patients with cancer reached 329,775 pesetas ($2,893). Cost of the health-care staff was the largest budget item in relation to the total health resources estimated.     

Cervical cancer: Radiotherapy and hyperthermia

Background: For many years, the standard treatment of advanced cervical cancer has been radiotherapy (RT), including brachytherapy. The achievement of locoregional tumour control is essential for cure. Results of RT in early stages are reasonably satisfactory, but locoregional failure rates for stage IIIb and IVa are high. In several randomized trials, the addition of hyperthermia (HT) to RT has been investigated.

Randomized trials: The Dutch Deep Hyperthermia Trial was completed in 1996. In this trial a beneficial effect of additional hyperthermia was clearly demonstrated. Three-year locoregional control and overall survival rates were significantly higher in the RT?+?HT group than in the RT alone group, while radiation toxicity was not affected. Cost-per-life-year-gained was less than 4000 Euros. The results of this trial have led to the acceptance of RT plus HT as standard treatment for advanced cervical cancer in the Netherlands.

?Five trials conducted in Asia have been published, of which three showed significant better complete response, locoregional tumour control and/or disease-free survival rates. One trial showed a trend of better locoregional tumour control and one did not show any benefit.

Conclusion: Hyperthermia added to standard radiotherapy of locally advanced cervical tumours results in considerable therapeutic gain and is cost-effective. For a beneficial effect, the use of an adequate heating technique is an important requirement.     

Isoprostane levels in the urine of patients with prostate cancer receiving radiotherapy are not elevated

PURPOSE: Previous studies have demonstrated that urinary 8-iso-prostaglandin F (PGF)2alpha serves as a powerful biomarker of lipid peroxidation in diseases in which oxidative stress plays an important role in its pathophysiology. The goal of this study was to measure the urinary isoprostane levels in patients with prostate cancer treated with radiotherapy (RT) in an effort to determine whether isoprostane levels are elevated compared with in historical controls, whether the levels increase after RT, and whether such an increase would correlate positively with the degree of GU symptoms during treatment. METHODS AND MATERIALS: Urine samples were obtained before and during RT from patients enrolled on a recently reported Phase III trial examining the therapeutic efficacy of ibuprofen in decreasing the acute urinary symptoms of RT. Radioimmunoassays were performed on urine samples for 8-iso-PGF2alpha or 15-keto-dihydro-PGF2alpha. RESULTS: Fifteen patients provided samples both before and during RT. The levels of 8-iso-PGF(2alpha) and 15-keto-dihydro-PGF2alpha in the urine samples obtained before prostate RT (0.27 and 0.41 nmol/mmol creatinine) did not differ appreciably from the values observed in a normal cohort (0.27 and 0.46 nmol/mmol creatinine) and did not change after RT (0.23 and 0.37 nmol/mmol creatinine). CONCLUSION: We were unable to detect an increase in either 8-iso-PGF2alpha or 15-keto-dihydro-PGF2alpha in the urine of patients with prostate cancer compared with in historical normal controls. We were also unable to measure an increase in either of the eicosanoids during RT to the prostate gland.     

Multivariable modeling of radiotherapy outcomes, including dose-volume and clinical factors

PURPOSE: The probability of a specific radiotherapy outcome is typically a complex, unknown function of dosimetric and clinical factors. Current models are usually oversimplified. We describe alternative methods for building multivariable dose-response models. METHODS: Representative data sets of esophagitis and xerostomia are used. We use a logistic regression framework to approximate the treatment-response function. Bootstrap replications are performed to explore variable selection stability. To guard against under/overfitting, we compare several analytical and data-driven methods for model-order estimation. Spearman's coefficient is used to evaluate performance robustness. Novel graphical displays of variable cross correlations and bootstrap selection are demonstrated. RESULTS: Bootstrap variable selection techniques improve model building by reducing sample size effects and unveiling variable cross correlations. Inference by resampling and Bayesian approaches produced generally consistent guidance for model order estimation. The optimal esophagitis model consisted of 5 dosimetric/clinical variables. Although the xerostomia model could be improved by combining clinical and dose-volume factors, the improvement would be small. CONCLUSIONS: Prediction of treatment response can be improved by mixing clinical and dose-volume factors. Graphical tools can mitigate the inherent complexity of multivariable modeling. Bootstrap-based variable selection analysis increases the reliability of reported models. Statistical inference methods combined with Spearman's coefficient provide an efficient approach to estimating optimal model order.