Noninferiority of Local Control and Comparable Toxicity of Intensity Modulated Radiation Therapy With Simultaneous Integrated Boost in Breast Cancer: 5-Year Results of the IMRT-MC2 Phase III Trial.

PURPOSE: The IMRT-MC2 trial was conducted to demonstrate the noninferiority of conventionally fractionated intensity modulated radiation therapy with a simultaneous integrated boost to 3-dimensional conformal radiation therapy with a sequential boost for adjuvant breast radiation therapy. METHODS AND MATERIALS: A total of 502 patients were randomized between 2011 and 2015 for the prospective, multicenter, phase III trial (NCT01322854). Five-year results of late toxicity (late effects normal tissue task force-subjective, objective, management, and analytical), overall survival, disease-free survival, distant disease-free survival, cosmesis (Harvard scale), and local control (noninferiority margin at hazard ratio [HR] of 3.5) were analyzed after a median follow-up of 62 months. RESULTS: The 5-year local control rate for the intensity modulated radiation therapy with simultaneous integrated boost arm was non-inferior to the control arm (98.7% vs 98.3%, respectively; HR, 0.582; 95% CI, 0.119-2.375; P = .4595). Furthermore, there was no significant difference in overall survival (97.1% vs 98.3%, respectively; HR, 1.235; 95% CI, 0.472-3.413; P = .6697), disease-free survival (95.8% vs 96.1%, respectively; HR, 1.130; 95% CI, 0.487-2.679; P = .7758), and distant disease-free survival (97.0% vs 97.8%, respectively; HR, 1.667; 95% CI, 0.575-5.434; P = .3601). After 5 years, late toxicity evaluation and cosmetic assessment further showed no significant differences between treatment arms. CONCLUSIONS: The 5-year results of the IMRT-MC2 trial provide strong evidence that the application of conventionally fractionated simultaneous integrated boost irradiation for patients with breast cancer is both safe and effective, with noninferior local control compared with 3-dimensional conformal radiation therapy with sequential boost.

Methods of Esthetic Assessment after Adjuvant Whole-Breast Radiotherapy in Breast Cancer Patients: Evaluation of the BCCT.core Software and Patients' and Physicians' Assessment from the Randomized IMRT-MC2 Trial.

The present analysis compares the esthetics assessment by the BCCT.core software in relation to patients' and physicians' ratings, based on the IMRT-MC2 trial. Within this trial, breast cancer patients received breast-conserving surgery (BCS) and adjuvant radiotherapy. At the baseline, 6 weeks, and 2 years after radiotherapy, photos of the breasts were assessed by the software and patients' and physicians' assessments were performed. Agreement rates of the assessments and their correlation with breast asymmetry indices were evaluated. The assessments of the software and the physicians were significantly correlated with asymmetry indices. Before and 6 weeks after radiotherapy, the patients' self-assessment was only correlated with the lower breast contour (LBC) and upward nipple retraction (UNR), while after 2 years, there was also a correlation with other indices. Only a slight agreement between the BCCT.core software and the physicians' or patients' assessment was seen, while a moderate and substantial agreement was detected between the physicians' and the patients' assessment after 6 weeks and 2 years, respectively. The BCCT.core software is a reliable tool to measure asymmetries, but may not sufficiently evaluate the esthetic outcome as perceived by patients. It may be more appropriate for a long-term follow-up, when symmetry appears to increase in importance.

Pressure-Volume Curve during Capnoperitoneum in Cats.

Laparoscopy is a growing field in veterinary medicine, although guidelines are lacking. The objective of this study was to evaluate the pressure-volume curve during capnoperitoneum in cats. A total of 59 female cats were scheduled for routine laparoscopy. Pressure and volume data were recorded and processed, and the yield point of the curve was calculated using a method based on a capacitor discharging function. For the remaining 40 cats, a linear-like pressure-volume curve was observed until a yield point with a mean cutoff pressure (COP) of 6.44 ± 1.7 mmHg (SD) (range, 2.72-13.00 mmHg) and a mean cutoff volume (COV) of 387 ± 144.35 mL (SD) (range, 178.84-968.43 mL) was reached. The mean mL/kg CO2 value in cats was 208 ± 34.69 mL/kg (range, 100.00-288.46 mL/kg). The COV correlated with COP and body weight but not with body condition score (BCS). COP correlated only with the COV. This study suggests that feline patients have a pressure-volume curve similar to that of canine patients, and the same pressure limit recommendations can be used for both species. After a yield point of 6.44 mmHg is reached, the increment in volume decreases exponentially as the intra-abdominal pressure (IAP) increases.

Influence of body weight and body conformation on the pressure-volume curve during capnoperitoneum in dogs.

OBJECTIVE To evaluate the pressure-volume relationship during capnoperitoneum in dogs and effects of body weight and body conformation. ANIMALS 86 dogs scheduled for routine laparoscopy. PROCEDURES Dogs were allocated into 3 groups on the basis of body weight. Body measurements, body condition score, and body conformation indices were calculated. Carbon dioxide was insufflated into the abdomen with a syringe, and pressure was measured at the laparoscopic cannula. Volume and pressure data were processed, and the yield point, defined by use of a cutoff volume (COV) and cutoff pressure (COP), was calculated. RESULTS 20 dogs were excluded because of recording errors, air leakage attributable to surgical flaws, or trocar defects. For the remaining 66 dogs, the pressure-volume curve was linear-like until the yield point was reached, and then it became visibly exponential. Mean ± SD COP was 5.99 ± 0.805 mm Hg. No correlation was detected between yield point, body variables, or body weight. Mean COV was 1,196.2 ± 697.9 mL (65.15 ± 20.83 mL of CO2/kg), and COV was correlated significantly with body weight and one of the body condition indices but not with other variables. CONCLUSION AND CLINICAL RELEVANCE In this study, there was a similar COP for all dogs of all sizes. In addition, results suggested that increasing the abdominal pressure after the yield point was reached did not contribute to a substantial increase in working space in the abdomen. No correlation was found between yield point, body variables, and body weight.

Atypical twin-to-twin transfusion syndrome: prevalence in a population undergoing fetoscopic laser ablation of communicating placental vessels.

BACKGROUND: The diagnosis of twin-to-twin transfusion syndrome (TTTS) usually relies the presence of polyhydramnios in one sac with concomitant oligohydramnios in the other sac in a monochorionic diamniotic twin pregnancy. However, TTTS does not always show a linear progression and may present with cardiac compromise or critically abnormal Doppler velocimetry in either fetus before fluid measurements meet the typically used cutoff. OBJECTIVE: The aim of this study was to investigate the prevalence of atypical presentations of TTTS in a population undergoing laser fetoscopy. STUDY DESIGN: We performed a retrospective review of our database of TTTS laser fetoscopy from 2003 to the present. Our center is the regional referral center in the Pacific Northwest for minimally invasive treatment of complicated monochorionic twin pregnancies. Cases were labeled as "atypical" if fluid discordance did not meet formal TTTS criteria (oligohydramnios defined as maximum vertical pocket [MVP] <2 and polyhydramnios defined as MVP >8 before 20 weeks and >10 after 20 weeks). The rationale for consideration of laser fetoscopy was other evidence of severe TTTS such as significant cardiac compromise, evidence of twin anemia polycythemia sequence (TAPS), or persistent critically abnormal cord Dopplers. RESULTS: Three hundred seventy-nine cases of fetoscopic laser ablation for TTTS and its variants were available for review. Sixteen cases were excluded for a triplet pregnancy, 4 due to septostomy prior to referral to our center, 3 for monoamniotic pregnancy, and 11 for previous laser fetoscopy. Three hundred forty-five cases remained for evaluation. Among these, 25 cases were identified as "atypical," equaling 7.24% of our population. Eleven of these were for stage 3 recipient disease, 3 were for stage 4 recipient disease, 4 were for stage 3 both in recipient and donor, 4 were for stage 3 donor disease, and 3 were for spontaneous TAPS. CONCLUSION: In TTTS, severity of fetal compromise does not consistently correlate with fluid abnormalities meeting established criteria. This may be especially true in rapidly progressing cases. Attempts at rigid diagnostic amniotic fluid criteria may underestimate the severity and incidence of TTTS. This underscores the importance of careful surveillance, including arterial and venous Doppler velocimetry, of all monochorionic pregnancies.

Impact of cold ischemia on mitochondrial function in porcine hearts and blood vessels.

The effects of cold storage using Custodiol® (Histidine-Tryptophan-Ketoglutarate, HTK) or isotonic saline solution on mitochondrial function in hearts (left and rights ventricles) and various blood vessels of pigs were investigated. Hearts, saphenous veins, internal-mammary-arteries and aortas of male landrace pigs were harvested and exposed to cold ischemia in either saline or Custodiol-HTK solution. Mitochondrial function was measured in situ in permeabilized fibers by high-resolution respirometry. Mitochondrial respiratory capacities (maximal respiration rates) were similar in the right and left ventricle in controls and after 14 h of cold storage were significantly better preserved in Custodiol-HTK than in saline solution. Mitochondrial respiration rates in various blood vessels including aorta, arteries and veins were less than 5% of myocardium rates. In contrast to the pig heart, in some blood vessels, like veins, mitochondrial function remained stable even after 24 h of cold ischemia. HTK-Custodiol protection of mitochondrial function after prolonged cold ischemia was observed in the myocardium but not in blood vessels. HTK-Custodiol solution thus offers significant protection of myocardial mitochondria against cold ischemic injury and can be used as efficient preservation solution in organ transplantation but probably has no benefit for blood vessels preservation. Analysis of mitochondrial function can be used as a valuable approach for the assessment of cold ischemic injury in various tissues including pig heart and various blood vessels.