Racecadotril Versus Loperamide in Acute Radiation Enteritis: A Randomized, Double-Masked, Phase 3, Noninferiority Trial.

PURPOSE: There is currently no gold standard for the management of acute radiation enteritis. We compared the efficacy and safety of Racecadotril, an anti-hypersecretory drug, versus Loperamide, an anti-motility agent, in acute radiation enteritis. METHODS AND MATERIALS: We conducted a randomized, double-masked, non-inferiority trial at a single research institute. Patients receiving curative radiation for pelvic malignancies, who developed grade 2 or 3 diarrhea (as per Common Terminology Criteria for Adverse Events, v 4.0) were included in the study. Patients in the intervention arm received Racecadotril and placebo. Patients in the control arm received Loperamide and placebo. The primary outcome was the resolution of diarrhea, 48 hours after the start of treatment. RESULTS: 162 patients were randomized between 2019 and 2022. On intention-to-treat analysis, 68/81 patients, 84%, (95% CI, 74.1%-91.2%) in the Racecadotril arm and 70/81, 86.4%, (95% CI, 77.0%-93.0%) in the Loperamide arm improved from grade 2 or 3 diarrhea to grade 1 or 0, (P= .66, χ2 test). The difference in proportion was 2.4% (95% CI: -8.5% to 13.4%). Since the upper boundary of the 95% CI crossed our non-inferiority margin of 10% (13.4%) we could not prove the non-inferiority of Racecadotril over Loperamide. Rebound constipation was more in the Loperamide arm compared to Racecadotril (17.3% vs 6.2%; P = .028) CONCLUSIONS: The non-inferiority of Racecadotril to Loperamide in acute radiation enteritis could not be demonstrated. However, Racecadotril can be the preferred drug of choice in acute radiation enteritis because Racecadotril does not affect bowel motility, achieved a high clinical success rate similar to that of Loperamide, and was associated with lesser side effects.

Does Radiation Dose to Gastric Fundus during Neoadjuvant Chemoradiotherapy for Esophageal Carcinoma Have an Impact on Postoperative Anastomotic Leak?

BACKGROUND: Radiation dose received by the gastric fundus (GF) in neoadjuvant chemoradiotherapy (NACRT) may influence the development of postoperative anastomotic leak (AL) in the management of resectable esophageal carcinoma (EC) by trimodality therapy. The present study aims to evaluate dose-volume parameters of the GF and their association with occurrence of AL in EC. MATERIALS AND METHODS: A retrospective analysis was performed of 27 patients with EC who underwent NACRT followed by esophagectomy with cervical esophagogastric anastomosis between January 2015 and July 2018. The GF was retrospectively contoured; dose-volume parameters of the GF were recorded. Postoperative AL was identified from surgical records. Logistic regression analysis was used to identify risk factors associated with AL. RESULTS: The mean age of the patients was 51 ± 10.5 years; 56% (15/27) had involvement of lower 1/3 esophagus, 10/27 (37%) midthoracic esophagus, and 2/27 (7%) upper thoracic esophagus; 40% (11/27) patients developed postoperative AL and 7/11 had distal and 4/11 had mid thoracic esophageal lesions. Four of five (80%) patients treated by 3-dimensional conformal radiotherapy versus 7/22 (32%) patients treated by volumetric modulated arc therapy developed AL (p = 0.12). Univariate logistic regression revealed no significant correlation between Dmean, Dmax, V20, V25, V30, V35, D50, and AL. 8/27 patients underwent ischemic preconditioning of gastric conduit, and 2/8 had AL; 19/27 did not undergo preconditioning, and 9/19 patients experienced AL (p = 0.4). CONCLUSION: There was no significant negative impact of the dose received by the GF in NACRT upon AL rates. Further studies with a larger sample size are required to clarify this issue.

Effect of Hypofractionated, Palliative Radiotherapy on Quality of Life in Late-Stage Oral Cavity Cancer: A Prospective Clinical Trial.

CONTEXT: The study was designed to evaluate the effect of a hypofractionated, palliative conformal radiotherapy regimen of 5250 cGy in 15 fractions in inoperable/incurable oral cavity carcinoma. AIMS: The primary objective was to assess the change in the quality of life (QOL) with respect to pain and mouth opening pre- and post-radiotherapy using standardized questionnaires. The secondary objective was to assess overall QOL using the same questionnaires and also to assess response rates, survival, compliance, early and late toxicity. SETTINGS AND DESIGN: This was a single-arm, prospective trial. Patients with incurable oral cavity cancer referred for palliative intent radiotherapy to the Department of Radiotherapy, RCC, JIPMER were recruited into the study. SUBJECTS AND METHODS: Forty-eight patients were recruited and twenty-five patients were given conformal radiotherapy to a dose of 52.5 Gy in 15 fractions. QOL was assessed using the European Organization of Research and Treatment of Cancer (EORTC) questionnaires before and 2 months after the completion of radiotherapy. The response assessment was made using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria 2 months after radiotherapy. The early and late toxicities were assessed at 2 months and 6 months after radiotherapy completion, respectively. STATISTICAL ANALYSIS USED: Sample size was calculated to be 53. The Wilcoxon signed-rank test was used to compare QOL scores pre- and post-radiotherapy. Median survival was assessed using the Kaplan-Meier method. RESULTS: There was a significant improvement in the pain, mouth opening, speech, social contact, social eating, felt ill items of the EORTC QLQ-H and N35 questionnaire and role functioning, emotional functioning, social functioning, fatigue, pain, insomnia, appetite loss, financial difficulties, and Global QOL subscales of the QLQ-C30 questionnaire. 72% of the patients had grade 3 acute radiation oral mucositis and 36% had grade 3 acute radiation dermatitis. There were no significant treatment breaks due to toxicity. There were no grade 3 late toxicities observed. Overall median survival was 5.1 months. The overall response rate was 47%. The median time to treatment completion was 24 days. CONCLUSIONS: The improvement in QOL parameters suggests that the regimen of 52.5 Gy in 15 fractions is suitable for palliative intent radiotherapy in late-stage oral cavity cancer for effective palliation for short periods.

Comparison of dosimetric parameters of volumetric modulated arc therapy and three-dimensional conformal radiotherapy in postmastectomy patients with carcinoma breast.

OBJECTIVE: Our study was undertaken to compare the dosimetric parameters of volumetric modulated arc therapy (VMAT) and three-dimensional conformal radiotherapy (3DCRT) in postmastectomy patients with left-sided carcinoma breast. STUDY DESIGN: This was a hospital-based cross-sectional study. MATERIALS AND METHODS: Thirty plans were generated - VMAT with two partial arcs and field in field tangential 3DCRT plans. RESULTS: In the 3DCRT plans, planning target volume (PTV) dose coverage was 2% higher compared with the VMAT plan 98.21 ± 1.79 versus 96.30 ± 2.62 (P = 0.028). The conformity index was better for the 3DCRT plan (0.97 vs. 0.95; P = 0.022), while the homogeneity index was worse for the VMAT plans (0.16 vs. 0.23; P = 0.057). However, the organ at risk sparing was better with the VMAT plans when compared to the 3DCRT plans. This was particularly relevant for the higher doses. The V20 Gy (34.94 vs. 24.42), V30 Gy (32.32 vs. 16.19), and V40 Gy (28.23 vs. 8.03) for the lung were significantly higher for the 3DCRT plans when compared to VMAT plans (P = 0.000). Similarly, the V20 Gy (29.88 vs. 12.79), V30 Gy (27.25 vs. 4.94), and V40 Gy (24.58 vs. 1.47) for the heart was significantly higher for the 3DCRT plans when compared to the VMAT plans (P = 0.000). The V5 Gy for lung (77.86 vs. 47.38) and heart (76.18 vs. 39.36) was significantly higher for the VMAT plans when compared to the 3DCRT plans (P = 0.000). CONCLUSION: VMAT is dosimetrically superior to the field-in-field 3DCRT for left-sided breast cancer patients owing to its comparable PTV coverage and better sparing of heart and lung.

Efficacy and safety of argon plasma coagulation in the management of extensive chronic radiation proctitis after pelvic radiotherapy for cervical carcinoma.

INTRODUCTION: Chronic radiation proctitis (CRP) usually develops 90 days or more after radiation. Currently, there is no standard available for the treatment of CRP. In argon plasma coagulation, monopolar diathermy is used to ionise the argon gas which coagulates the telengiectatic vessels in a noncontact fashion. However, there are very few studies which have reported its use in extensive CRP. We report the efficacy and safety of APC in seven patients with recurrent, extensive grade 3 radiation proctitis. MATERIALS AND METHODS: This is a retrospective analysis of patients treated with argon plasma coagulation in our institute from June 2013 to June 2016. After adequate bowel preparation, patients underwent APC at an average power of 50 W with flow rate of 5 L/min. All the visible telangiectasia was ablated which required many sittings. RESULTS: The median RPSAS symptom score for frequency of bleeding at enrolment was 5 (range 3-5). After completion of APC, the median RPSAS symptom score for frequency of bleeding decreased to 1. The median RPSAS symptom score for severity of bleeding was 5 (range 3-5). After completion of APC, the mean RPSAS symptom score for severity of bleeding decreased to 1. Mean haemoglobin level before treatment was 5.43 g/dl (SD 2.37). Mean haemoglobin level after treatment was10.04 g/dl (SD 2.0). Compared with pre-treatment levels after APC, there was a mean increase in haemoglobin of 4.61 + 1.78 [95% CI 2.97-6.25, p = 0.00]. CONCLUSION: Argon plasma coagulation is a safe, well tolerated and effective treatment option in extensive chronic radiation proctitis which is refractory to medical management.