Correlates and Trajectories of Preterm Infant Sucking Patterns and Sucking Organization at Term Age.

BACKGROUND: Premature infants may experience increased difficulty with nutrition and growth. Successful oral feeding is an important factor associated with discharge readiness. Despite the importance of feeding as a growth-fostering process, little empiric evidence exists to guide recommendations for early interventions. PURPOSE: Evaluate whether specific elements of sucking, during preterm initiation of oral feeding, predict sucking organization at corrected term age. METHODS: Sucking performance of 88 preterm infants born between 24 and 34 weeks of post-menstrual age was measured at baseline and term (33-35 and 40 ± 1.5 weeks). Participants were divided into 4 groups (quartiles) based on initial measures of performance including number of sucks, number of bursts, sucks per burst, and maximum pressure. Stability in sucking organization was assessed by comparing changes in infant's quartile location from baseline to term. RESULTS: A correlation between quartile location was observed for mean maximum pressure (PMAX): infants with PMAX in the lowest quartile (poorest performance) were significantly more likely to remain in the lowest quartile at term (P < .000); infants in the highest quartile (best performance) at baseline were significantly more likely to be in the highest quartile at term (P < .000). IMPLICATION FOR PRACTICE: Infants with the weakest sucking pressures at 34 weeks of post-menstrual age continue to be at risk for less than optimal feeding skills at 40 weeks of post-menstrual age. Early identification of at-risk infants may allow for effective interventions to potentially decrease long-term feeding problems. IMPLICATIONS FOR RESEARCH: Future research should focus on the development of personalized interventions to address attributes of problematic feeding such as sucking efficiency.

Stereotactic central/core ablative radiation therapy: results of a phase I study of a novel strategy to treat bulky tumor.

Purpose: Bulky tumor remains as a challenge to surgery, chemotherapy and conventional radiation therapy. Hence, in efforts to overcome this challenge, we designed a novel therapeutic paradigm via strategy of Stereotactic Central/Core Ablative Radiation Therapy (SCART).), which is based on the principles of SBRT (stereotactic body radiation therapy and spatially fractionated radiation therapy (SFRT). We intend to safely deliver an ablative dose to the core of the tumor and with a low dose at tumor edge. The purpose of the phase 1 study was to determine dose-limiting toxicities (DLT)s and the Maximum Tolerated Dose (MTD) of SCART. Methods and materials: We defined a SCART-plan volume inside the tumor, which is proportional to the dimension of tumor. VMAT/Cyberknife technique was adopted. In the current clinical trial; Patients with biopsy proven recurrent or metastatic bulky cancers were enrolled. The five dose levels were 15 Gy X1, 15Gy X3, 18GyX3, 21GyX3 and 24GyX3, while keeping the whole tumor GTV's border dose at 5Gy each fraction. There was no restriction on concurrent systemic chemotherapy agents. Results: 21 patients were enrolled and underwent SCART. All 21 patients have eligible data for study follow-up. Radiotherapy was well tolerated with all treatment completed as scheduled. The dose was escalated for two patients to 24GyX3. No grade 3 or higher toxicity was observed in any of the enrolled patients. The average age of patients was 66 years (range: 14-85) and 13 (62%) patients were male. The median SCART dose was 18Gy (range: 15 - 24). Six out of the 18 patients with data for overall survival (OS) died, and the median time to death was 16.3 months (range: 1 - 25.6). The mean percent change for tumor shrinkage between first visit volumes and post-SCART volumes was 49.5% (SD: 40.89, p-value:0.009). Conclusion: SCART was safely escalated to 24 GyX 3 fractions, which is the maximum Tolerated Dose (MTD) for SCART. This regimen will be used in future phase II trials.

Cerebral Blood Flow, Brain Injury, and Aortic-Pulmonary Collateral Flow After the Fontan Operation.

Patients with a single ventricle develop aortopulmonary collaterals (APCs) whose flow has been shown to be inversely proportional to cerebral blood flow (CBF) in a previous cross-sectional study. Longitudinal CBF and APC flow in patients with Fontan physiology adjusting for brain injury (BI) has never been reported. Decreased CBF and BI may adversely impact neurodevelopment. A prospective longitudinal cohort of 27 patients with Fontan physiology (aged 10 ± 1.9 years, 74% male) underwent cardiac and brain magnetic resonance imaging 3 to 9 months and 6.0 ± 1.86 years after Fontan operation to measure the CBF and APC flow and to reassess the BI (focal BI, generalized insult, and hemorrhage). CBF was measured using jugular venous flow and APC flow was measured by the difference between aortic flow and caval return. Multivariate modeling was used to assess the relation between the change in APC flow and BI. A strong inverse relation was found between CBF/aortic flow change and APC flow/aortic flow and APC flow/body surface area change (R2 = 0.70 and 0.72 respectively, p <0.02). Overall, the CBF decreased by 9 ± 11% and the APC flow decreased by 0.73 ± 0.67 l/min/m2. The evolution of CBF and APC flow were significantly and inversely related when adjusting for time since Fontan operation, gender, and BI on the multivariate modeling. Every unit increase in APC flow change was associated with an 8% decrease in CBF change. In conclusion, CBF and APC flow change are inversely related across serial imaging, adjusting for time from Fontan operation, gender, and BI. CBF and APC aortic flow decrease over a 6-year period. This may adversely impact neurodevelopment. Because APCs can be embolized, this may be a modifiable risk factor. Clinical trials numbers: NCT02135081 and NCT02919956.

Risk of peripartum hysterectomy by mode of delivery and prior obstetric history: data from a population-based study.

PURPOSE: To provide an estimate of the incidence of peripartum hysterectomy in the state of New Jersey and calculate the effect of mode of delivery and prior obstetric history. METHODS: A perinatal-linked dataset provided by the Maternal Child Health Epidemiology Program in the New Jersey Department of Health was used to obtain information from birth certificates and hospital discharge records. Using multivariate logistic regression, various demographic and clinical factors were assessed for association with peripartum hysterectomy. RESULTS: A total of 1,004,116 births were identified between 1997 and 2005 and 853 peripartum hysterectomies were performed (0.85/1,000 deliveries). Parity increased the risk of hysterectomy with nulliparous women having approximately half the risk compared to multiparous women. Cesarean delivery with no previous c-section almost doubled the risk (OR 2.20, CI 1.80-26.69) while in the presence of a previous c-section the risk was almost four times higher (OR 4.51, CI 3.76-5.40). Operative vaginal delivery did not result in any increase in the risk. CONCLUSIONS: Mode of delivery and prior obstetric history are major risk factors for peripartum hysterectomy. Patients desiring cesarean delivery need to be counseled on the risk of this serious complication.

Salvage Fractionated Stereotactic Radiotherapy with or without Chemotherapy and Immunotherapy for Recurrent Glioblastoma Multiforme: A Single Institution Experience.

BACKGROUND: The current standard of care for salvage treatment of glioblastoma multiforme (GBM) is gross total resection and adjuvant chemoradiation for operable patients. Limited evidence exists to suggest that any particular treatment modality improves survival for recurrent GBM, especially if inoperable. We report our experience with fractionated stereotactic radiotherapy (fSRT) with and without chemo/immunotherapy, identifying prognostic factors associated with prolonged survival. METHODS: From 2007 to 2014, 19 patients between 29 and 78 years old (median 55) with recurrent GBM following resection and chemoradiation for their initial tumor, received 18-35 Gy (median 25) in three to five fractions via CyberKnife fSRT. Clinical target volume (CTV) ranged from 0.9 to 152 cc. Sixteen patients received adjuvant systemic therapy with bevacizumab (BEV), temozolomide (TMZ), anti-epidermal growth factor receptor (125)I-mAb 425, or some combination thereof. RESULTS: The median overall survival (OS) from date of recurrence was 8 months (2.5-61) and 5.3 months (0.6-58) from the end of fSRT. The OS at 6 and 12 months was 47 and 32%, respectively. Three of 19 patients were alive at the time of this review at 20, 49, and 58 months from completion of fSRT. Hazard ratios for survival indicated that patients with a frontal lobe tumor, adjuvant treatment with either BEV or TMZ, time to first recurrence >16 months, CTV <36 cc, recursive partitioning analysis <5, and Eastern Cooperative Oncology Group performance status <2 were all associated with improved survival (P < 0.05). There was no evidence of radionecrosis for any patient. CONCLUSION: Radiation Therapy Oncology Group (RTOG) 1205 will establish the role of re-irradiation for recurrent GBM, however our study suggests that CyberKnife with chemotherapy can be safely delivered, and is most effective in patients with smaller frontal lobe tumors, good performance status, or long interval from diagnosis.

Rates of Reconstruction Failure in Patients Undergoing Immediate Reconstruction With Tissue Expanders and/or Implants and Postmastectomy Radiation Therapy.

OBJECTIVES: Mastectomy rates for breast cancer have increased, with a parallel increase in immediate reconstruction. For some women, tissue expander and implant (TE/I) reconstruction is the preferred or sole option. This retrospective study examined the rate of TE/I reconstruction failure (ie, removal of the TE or I with the inability to replace it resulting in no final reconstruction or autologous tissue reconstruction) in patients receiving postmastectomy radiation therapy (PMRT). METHODS AND MATERIALS: Between 2004 and 2012, 99 women had skin-sparing mastectomies (SSM) or total nipple/areolar skin-sparing mastectomies (TSSM) with immediate TE/I reconstruction and PMRT for pathologic stage II to III breast cancer. Ninety-seven percent had chemotherapy (doxorubicin and taxane-based), 22% underwent targeted therapies, and 78% had endocrine therapy. Radiation consisted of 5000 cGy given in 180 to 200 cGy to the reconstructed breast with or without treatment to the supraclavicular nodes. Median follow-up was 3.8 years. RESULTS: Total TE/I failure was 18% (12% without final reconstruction, 6% converted to autologous reconstruction). In univariate analysis, the strongest predictor of reconstruction failure (RF) was absence of total TE/I coverage (acellular dermal matrix and/or serratus muscle) at the time of radiation. RF occurred in 32.5% of patients without total coverage compared to 9% with coverage (P=.0069). For women with total coverage, the location of the mastectomy scar in the inframammary fold region was associated with higher RF (19% vs 0%, P=.0189). In multivariate analysis, weight was a significant factor for RF, with lower weight associated with a higher RF. Weight appeared to be a surrogate for the interaction of total coverage, thin skin flaps, interval to exchange, and location of the mastectomy scar. CONCLUSIONS: RFs in patients receiving PMRT were lowered with total TE/I coverage at the time of radiation by avoiding inframammary fold incisions and with a preferred interval of 6 months to exchange.

Prostate seed implantation using 3D-computer assisted intraoperative planning vs. a standard look-up nomogram: Improved target conformality with reduction in urethral and rectal wall dose.

PURPOSE: To compare dosimetric outcomes between two real-time prostate seed implantation (PSI) techniques to evaluate the impact of three-dimensional (3D) intraoperative computer planning on target coverage, conformality, and preset urethral and rectal dose constraints. METHODS AND MATERIALS: One hundred and fourteen patients with clinically localized prostate cancer underwent ultrasound-guided transperineal PSI of the prostate with (125)I sources as monotherapy. From 1999 to 2001, 69 patients were implanted in real-time using a standard look-up nomogram (Group 1: NG-PSI). All patients were implanted with a modified peripheral loading technique in which 75-80% of the calculated total activity was delivered to the gland periphery, with the remaining 20-25% activity placed in the gland interior, to achieve a prescribed dose (PD) of 144 Gy to cover the gland with acceptable homogeneity. No preoperative or intraoperative planning was performed to set dose constraints to the urethra or anterior rectal wall. Dosimetric outcome from this group was compared with 45 patients subsequently implanted after 2001 using an intraoperative 3D computer planning system (Group 2: 3D-PSI). A similar modified peripheral loading technique was used as an option in the planning system. Preoperative dose constraints were placed on the urethra (V150 < 35%), prostate (V100 > 95% of PD; D90: 140-180 Gy), and rectal wall (V110 < 1.5 cc) with real-time dosimetric feedback performed after peripheral loading. Manual dose optimization was performed to determine interior needle position and remaining number and placement of (125)I sources to adhere to urethral and rectal constraints and target coverage goals. Both groups underwent postimplant CT analysis to determine dosimetric outcome with regard toV100(prostate), D90(prostate), V150(urethra), and V110(rectum). Univariate and multivariate analysis was performed to determine variables impacting on dosimetric outcome. RESULTS: Analysis of preimplant and postimplant variables demonstrated no difference in the median preimplant gland volume (33 cc vs. 35 cc; p = 0.31), median mCi/seed strengths (0.4 vs. 0.45 mCi; p = 0.23), median V100 (94% vs. 94%), or median D90 at postimplant Day 30 (165 Gy vs. 160 Gy; p = 0.26) between Groups 1 and 2. However, for Group 2 (3D-PSI) the median total mCi implanted (26 vs. 33 mCi; p < 0.0001) and the median number of seeds implanted (67 vs. 83; p < 0.0001) were reduced substantially. The percent of patients exceeding a D90 > 180 Gy was reduced from 29% in Group 1 to 16% in Group 2 (p = 0.08). A reduction was observed in the percent of patients receiving a D90 < 140 Gy (14% Group 1 vs. 9% Group 2, p = 0.56). The median V150(urethra) for Group 2 was reduced dramatically with 3D-PSI compared with NG-PSI (63% vs. 17%; p < 0.0001). A V150(urethra) > 30% was observed in 88% in Group 1 compared with 29% in Group 2, p < 0.0001. Similarly, the median V110(rectum) for Group 1 was significantly higher than that in Group 2 (1.93 vs. 0.26 cc; p < 0.0001). The percent of patients with V110(rectum) > 1.5 cc in Group 1 and Group 2 was 57% and 13%, respectively (p < 0.0001). CONCLUSIONS: The adoption of 3D computer intraoperative dose planning and optimization for prostate seed implantation resulted in dramatic reductions in urethral and rectal wall doses, while consistently producing excellent target coverage with reduced dose variability above 180 Gy and below 140 Gy, compared with the use of a standard look-up nomogram. Additionally, the reduction in total mCi and number of seeds needed to achieve improved conformality was substantial and may have implications for cost savings.

Prostate implant dosimetric outcomes and migration patterns between bio-absorbable coated and uncoated brachytherapy seeds.

PURPOSE: To evaluate the lung and pelvic seed migration and intraprostatic dose variability for prostate seed implant (PSI) using bio-absorbable polymer "coated" seeds for intraoperative planning. METHODS AND MATERIALS: A total of 100 PSI patients were initially implanted with uncoated I-125 (STM 1251 or I125-SL, N = 85) or Pd-103 (mod 200, N = 15) seeds, and 105 PSI patients were implanted subsequently with coated seeds using inverse optimization with real-time planning. Implant technique, average number of needles, and dose objectives remained identical among the cohorts. RESULTS: Day 30 postimplant comparison of seed migration demonstrated a significant reduction in overall lung and pelvic seed migration from 25% (uncoated) to 4% (coated) (p < 0.0001). A measurable reduction in intraprostatic dose variability was observed in patients with the coated seeds when comparing 30 days dosimetry results for V100, V150, and D90 for prostate, and V110 for the rectum. A statistically significant reduction in the standard deviation from Day 0 to Day 30 for the above parameters for the prostate as well as for V110 of rectum was also observed. A significant improvement in implant quality at Day 30 was demonstrated using Radiation Therapy Oncology Group (RTOG) evaluation criteria range with the coated seeds cohort. CONCLUSIONS: PSI using coated seeds shows lower lung and pelvic seed migration compared with those using uncoated seeds and compares favorably to pelvic stranded seed migration reports. A higher concordance was observed with less dose variability in dosimetric parameters on Day 30 dosimetry compared with that on Day 0. Improvement in the implant quality was also observed using the RTOG criteria, suggesting reduced intraprostatic migration.

Radiation therapy dose escalation for prostate cancer: a rationale for IMRT.

The response of prostate cancer to radiation was well-documented in the pre-PSA era. Large palpable tumors resolved within months of treatment with relatively modest radiation doses of 64-70 Gy. The use of PSA-based failure as an endpoint, however, has made it clear that cure rates were much lower than appreciated. While doses in this range are still widely used today, data from retrospective, sequential prospective and now randomized studies indicate that for patients with intermediate-to-high risk disease, doses above 70 Gy are associated with a significant reduction in biochemical failure. The use of 3D-conformal radiotherapy to escalate radiation dose has resulted in modest increases in rectal and bladder toxicity. The application of intensity modulated radiotherapy methods allows for greater sparing of the surrounding normal tissues and, hence, the potential to further escalate dose. The results of dose escalation, the ability of IMRT to reduce rectal and bladder exposure to high radiation doses and the use of new imaging methods to more accurately target the prostate are described.

An interinstitutional and interspecialty comparison of treatment outcome data for patients with prostate carcinoma based on predefined prognostic categories and minimum follow-up.

BACKGROUND: The optimal management of patients with clinically localized prostate carcinoma remains undefined due in part to the absence of well-designed, prospective, randomized trials. The current study was conducted to compare and contrast outcomes with different forms of therapy for patients with prostate carcinoma who were treated at several institutions using predefined prognostic categories. METHODS: A retrospective study of 6877 men with prostate carcinoma who were treated between 1989 and 1998 at 7 different institutions with 6 different types of therapy was conducted. Five-year actuarial rates of prostate specific antigen (PSA) failure were calculated based on predefined prognostic categories, which included combinations of pretreatment PSA level, tumor stage, and Gleason score. In addition, outcome was calculated using consistent biochemical failure definitions and a minimum, median length of follow-up. RESULTS: Substantial differences in outcome were observed for the same type of treatment and at the same institution, depending on the number of prognostic variables used to define treatment groups. However, estimates of 5-year PSA outcomes after all forms of therapy for low-risk and intermediate-risk patient groups were remarkably similar (regardless of the type of treatment) when all three pretreatment variables were used to define prognostic categories. For patients in high-risk groups, the 5-year PSA outcomes were suboptimal, regardless of the treatment technique used. CONCLUSIONS: The current data suggest that interinstitutional and interspecialty comparisons of treatment outcome for patients with prostate carcinoma are possible but that results must be based on all major prognostic variables to be meaningful. Analyzed in this fashion, 5-year PSA results were similar for patients in low-risk and intermediate-risk groups, regardless of the form of therapy. Findings from prospective, randomized trials using survival (cause specific and overall) as the end point for judging treatment efficacy and longer follow-up will be needed to validate these findings and to identify the most appropriate management option for patients with all stages of disease.