Elizabethkingia meningoseptica: emerging multidrug resistance in a nosocomial pathogen.

A 46-year-old male patient presented with complaints of burning micturition for 2 days. Initial history, physical examination and laboratory investigations were consistent with the diagnosis of congestive cardiac failure (CCF) and concomitant urinary tract infection. CCF was treated with diuretics and a urine culture/sensitivity (C/S) was sent which returned growing Elizabethkingia meningoseptica resistant to all tested drugs. Intravenous cefotaxime which had been started empirically 3 days earlier was withheld at this point, and a repeat urine C/S was sent revealing resistance to all tested drugs (including reserved drugs) barring minocycline. The patient was treated with oral minocycline for 14 days after which he was symptomatically better with sterile urine. The patient was subsequently discharged.

Intensity modulated radiation therapy (IMRT) is not superior to three-dimensional conformal radiation (3DCRT) for adjuvant gastric radiation: A matched pair analysis.

AIMS: To compare three-dimensional conformal radiation (3DCRT) and Intensity Modulated Radiation Therapy (IG-IMRT) for adjuvant gastric irradiation. SUBJECTS AND METHODS: From Jan 2010-Aug 2013, all patients undergoing 3DCRT and IG-IMRT were included. Systemic chemotherapy included 1 cycle before and 2 cycles after chemoradiation. Planning Target Volume (PTV) received 45 Gy/25 fractions/5 weeks with concurrent capcetabine 825 mg/m2 bid. Matched pair analysis was performed to evaluate imbalance in two cohorts if any. Common Toxicity Criteria for Adverse Event (CTCAE) vs 3.0 was used to record gastrointestinal (GI), hematological (HL), and renal toxicity during treatment and follow-up. Patterns of recurrence were documented. Mann-Whitney U test was used for statistical comparison. RESULTS: Of the 51 patients, 26 received 3DCRT and 25 IMRT. IMRT led to decrease in dose received by right and left kidney (12.4 Gy and 7.1 Gy and 29 Gy vs 8.2 Gy; P<0.001). Overall, 17.6% and 19.6% patients had grade II GI and HL toxicity and 3.9% and 5.9% had grade III GI and HL toxicity. No difference was observed in acute grade II-V GI or HL toxicity (11.5% vs 24%, P=0.07; 7.6% vs 20% P=0.20) or late GI, HL, or renal toxicity between 3DCRT and IMRT. No difference was observed in patterns of local relapse (11.5% vs 12%, P=0.14) or overall survival (39% and 38% (P=0.97)) between 3DCRT and IMRT. CONCLUSIONS: 3DCRT and IMRT are equivalent in terms of toxicity and local control.

Predictors of late bowel toxicity using three different methods of contouring in patients undergoing post-operative radiation for cervical cancer.

OBJECTIVE: This study investigates the correlation between dose-volume histogram derived from three bowel contouring methods and late toxicity in patients undergoing post-operative radiation therapy (PORT) for cervical cancer. METHODS: From June 2010 to May 2013, 103 patients undergoing PORT were included. Three different contouring methods were used: (a) individual small bowel (SB) and large bowel (LB) loops, (b) total bowel (TB; including SB and LB) and (c) peritoneal cavity (PC). The volume of SB, LB, TB and PC receiving 15, 30 and 40 Gy was calculated. Acute and late bowel toxicities were scored using Common Terminology Criteria for Adverse events v. 3.0. Receiver operating characteristic curve identified thresholds predicting late toxicity with the highest specificity. All data were dichotomized across these thresholds. Univariate and multivariate analyses were performed using SPSS(®) v. 20 (IBM Corporation, Armonk, NY; formerly SPSS Inc., Chicago, IL). RESULTS: On univariate analysis, V30 PC ≥ 900 cm(3) (p = 0.01), V40 PC ≥ 750 cm(3) (p = 0.03) and V40 TB ≥ 280 cm(3) (p = 0.03) and use of concurrent chemotherapy (p = 0.03) predicted grade ≥II acute toxicity. On multivariate analysis, use of concurrent chemotherapy [odds ratio (OR) 3.5, 95% confidence interval (CI) 1.1-11.1, p = 0.03] and V30 PC ≥ 900 cm(3) (OR 2.3, 95% CI 1-5.5, p = 0.05) predicted acute grade ≥II toxicity. On univariate analysis for late toxicity, SB (V30 ≥ 190 cm(3), p = 0.009; V40 ≥ 150 cm(3), p = 0.03), LB (V15 ≥ 250 cm(3), p = 0.04), V40 PC (V40 ≥ 750 cm(3), p = 0.001) and presence of acute grade ≥III toxicity (p = 0.006), treatment technique (three-dimensional conformal radiation or intensity modulated radiotherapy, p = 0.02) predicted more than or equal to grade ll late bowel toxicity. On multivariate analysis, only body mass index ≥25 kg m(-2) (OR 7.3, 95% CI 1.6-31.6, p = 0.008) and presence of acute grade III toxicity predicted toxicity (OR 5.1, 95% CI 1.4-18.1, p = 0.007). CONCLUSION: V30 PC ≥ 900 cm(3) and use of concurrent chemotherapy independently predicts acute toxicity. Presence of acute grade ≥III toxicity independently predicts late toxicity. Minimizing dose to PC subvolumes can therefore reduce both acute and late toxicities. ADVANCES IN KNOWLEDGE: Study establishes PC thresholds that can minimize both acute and late bowel toxicities.

Predictors of grade 3 or higher late bowel toxicity in patients undergoing pelvic radiation for cervical cancer: results from a prospective study.

PURPOSE: The present study investigates relationship between dose-volume parameters and severe bowel toxicity after postoperative radiation treatment (PORT) for cervical cancer. METHODS AND MATERIALS: From June 2010 to December 2012, a total of 71 patients undergoing PORT were included. Small bowel (SB) and large bowel (LB) loops were contoured 2 cm above the target volume. The volume of SB and LB that received 15 Gy, 30 Gy, and 40 Gy was calculated (V15 SB, V15 LB, V30 SB, V30 LB, V40 SB, V 40 LB). On follow-up, bowel toxicity was scored using Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. A reciever operating characteristic (ROC) curve identified volume thresholds that predicted for grade 3 or higher toxicity with highest specificity. All data was dichotomized across these identified cut-off values. Univariate and multivariate analysis was performed using SPSS, version 15. RESULTS: The median patient age was 47 years (range, 35-65 years). Of the 71 patients, 46 received image-guided intensity modulated radiation therapy, and 25 received conformal radiation (50 Gy in 25 fractions for 5 weeks). Overall, 63 of 71 patients received concurrent chemotherapy. On a median follow-up of 18 months (range, 8-29 months), grade 2 or higher bowel toxicity was seen in 22 of 71 patients (30.9%) and grade 3 or higher bowel toxicity was seen in 9 patients (12.6%). On univariate analysis, V15 SB <275 cc (P=.01), V30 SB <190 cc (P=.02), V40 SB <150 cc (P=.01), and V15 LB <250 cc (P=.03), and V40 LB <90 cc (P=.04) predicted for absence of grade 3 or higher toxicity. No other patient- or treatment-related factors were statistically significant. On multivariate analysis, only V15 SB (P=.002) and V15 LB (P=.03) were statistically significant. CONCLUSIONS: V 15 Gy SB and LB are independent predictors of late grade 3 or higher toxicity. Restricting V15 SB and V15 LB to <275 cc and <250 cc can reduce grade 3 or higher toxicity to less than 5%.

Evaluation of interobserver and interscale agreement in assessing late bowel toxicity after pelvic radiation in patients with carcinoma of the cervix.

BACKGROUND: Lack of agreement and inconsistency in capturing late bowel toxicity may be a source of error while reporting trials with toxicity endpoints. Documenting baseline inconsistency while scoring toxicity questionnaires (RTOG/EORTC and CTCAE) may be worthwhile. The present study was conducted as a quality assurance measure prior to initiating a randomized trial (PARCER; NCT01279135) that evaluates the impact of image-guided radiation on bowel toxicity. METHODS: From August 2010 to July 2011, patients with cervical cancer who underwent pelvic chemoradiation >6 months ago, with controlled disease and any bowel symptom at follow-up, were included. RTOG and CTCAE questionnaires were filled by two blinded observers. Interscale (RTOG vs CTCAE) and interobserver (observer A and B) agreement were evaluated with Spearman's correlation and kappa statistic. RESULTS: Fifty-five patients were included. Twelve patients with symptoms could not be graded by the RTOG scale. Of those graded as asymptomatic on RTOG, distension, vomiting, pain and nausea were identified as the most common symptoms. Amongst these, grade 1, 2 and 3 toxicity was observed in 6, 5 and 1 patient, respectively. The interscale correlation was moderate (Spearman's correlation ρ = 0.56; P = 0.001). High interobserver agreement (92%) was observed within the RTOG scale [kappa (κ) -0.94; 95% CI 0.77-1]. All disagreements were observed while scoring grade 1-2 toxicity. Among CTCAE, agreement was lower with modules such as distension, anorexia, nausea and constipation. CONCLUSIONS: High interobserver agreement was observed for both RTOG and most CTCAE subscales; most disagreements were for grade 1-2. Interscale agreement (RTOG and CTCAE) was moderate. Detailed patient interrogation or use of patient-reported-outcome scores while documenting the aforesaid subscales may be worthwhile.

Protocol for a phase III randomised trial of image-guided intensity modulated radiotherapy (IG-IMRT) and conventional radiotherapy for late small bowel toxicity reduction after postoperative adjuvant radiation in Ca cervix.

INTRODUCTION: External beam radiation followed by vaginal brachytherapy (±chemotherapy) leads to reduction in the risk of local recurrence and improves progression-free survival in patients with adverse risk factors following Wertheim's hysterectomy albeit at the risk of late bowel toxicity. Intensity Modulated Radiotherapy (IMRT) results in reduction in bowel doses and has potential to reduce late morbidity, however, needs to be confirmed prospectively in a randomised trial. The present randomised trial tests reduction if any in late small bowel toxicity with the use of IMRT in postoperative setting. METHODS AND ANALYSIS: Patients more than 18 years of age who need adjuvant (chemo) radiation will be eligible. Patients with residual pelvic or para-aortic nodal disease, history of multiple abdominal surgeries or any other medical bowel condition will be excluded. The trial will randomise patients into standard radiation or IMRT. The primary aim is to compare differences in late grades II-IV bowel toxicity between the two arms. The secondary aims of the study focus on evaluating correlation of dose-volume parameters and late toxicity and quality of life. The trial is planned as a multicentre randomised study. The trial is designed to detect a 13% difference in late grades II-IV bowel toxicity with an α of 0.05 and ß of 0.80. A total of 240 patients will be required to demonstrate the aforesaid difference. ETHICS AND DISSEMINATION: The trial is approved by institutional ethics review board and will be routinely monitored as per standard guidelines. The study results will be disseminated via peer reviewed scientific journals, conference presentations and submission to regulatory authorities. REGISTRATION: The trial is registered with clinicaltrials.gov (NCT 01279135).