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OBJECTIVE The aim of the study was to assess the impact of Electronic Health Record (EHR) implementation on medication safety in two intensive care units (ICUs). METHODS Using a prospective pre-post design, we assessed 1254 consecutive admissions to two ICUs before and after an EHR implementation. Each medication event was evaluated with regard to medication error (error type, medication-management stage) and impact on patient (severity of potential or actual harm). RESULTS We identified 4063 medication-related events either pre-implementation (2074 events) or post-implementation (1989 events). Although the overall potential for harm due to medication errors decreased post-implementation only 2 of the 3 error rates were significantly lower post-implementation. After EHR implementation, we observed reductions in rates of medication errors per admission at the stages of transcription (0.13-0, P < 0.001), dispensing (0.49-0.16, P < 0.001), and administration (0.83-0.56, P = 0.011). Within the ordering stage, 4 error types decreased post-implementation (orders with omitted information, error-prone abbreviations, illegible orders, failure to renew orders) and 4 error types increased post-implementation (orders of wrong drug, orders containing a wrong start or stop time, duplicate orders, orders with inappropriate or wrong information). Within the administration stage, we observed a reduction of late administrations and increases in omitted administrations and incorrect documentation. CONCLUSIONS Electronic Health Record implementation in two ICUs was associated with both improvement and worsening in rates of specific error types. Further safety improvements require a nuanced understanding of how various error types are influenced by the technology and the sociotechnical work system of the technology implementation. Recommendations based on human factors engineering principles are provided for reducing medication errors.

To investigate the clinical outcomes and toxicity in patients with locally advanced cervical cancer treated with supplementary applicator guided-intensity modulated radiation therapy (IMRT) based on conventional intracavitary brachytherapy (IC/IMRT).A retrospective cohort study.Sichuan Cancer HospitalInstitute, Sichuan Cancer Centre, China.Large high-risk clinical target volume (HR-CTV) volume (40 ml) at the time of brachytherapy cervical cancer patients were recruited.This study is a retrospective analysis of 76 patients with locally advanced cervical cancer (FIGO IIB-IVA) treated with concurrent chemoradiotherapy followed by IC/IMRT between June 2010 and October 2016. External radiotherapy (45 Gy in 25 fractions) was adminstered with cisplatin chemotherapy treatment before IC/IMRT. The IMRT plan was optimised using the ICBT plan base dose plan by an inverse dose optimisation tool which allows the use of DVH constraints on the total dose of ICBT. A seven-field gantry angle IMRT plan was devised to avoid hotspots when optimising the boost plan. The prescription dose for HR-CTV and IR-CTV were 6 and 5 Gy per fraction for five fractions, respectively.Mean HR-CTV was 65.8 ± 23.6 ml at the time of brachytherapy. D90 for HR-CTV and IR-CTV were 88.7 ± 3.6 Gy and 78.1 ± 2.5 Gy. D2cc for bladder, rectum, sigmoid and small intestine were 71.8 ± 3.8, 64.6 ± 4.9, 63.9 ± 5.3 and 56.7 ± 8.7 Gy, respectively. Median follow-up was 85 months (47.9-124.2 months). Five-year local recurrence-free survival rate, metastasis recurrence-free survival rate, disease-free survival rate and cancer-special survival rate were 87.6, 82.4, 70.9 and 76.3%, respectively. The grade 1 + 2 gastrointestinal and urinary late toxicities were 15.8 and 21.1%, and grade 3 late toxicities were 3.9 and 5.2%, respectively. Neither acute nor late grade 4 gastrointestinal or urinary toxicities were seen.The combination of ICBT with an applicator-guided supplementary IMRT boost achieved excellent local control and overall survival with low toxicity for bulky residual cervical tumour.

Objective Geographic atrophy (GA), a late stage of age-related macular degeneration, is a major cause of irreversible blindness. Even while central visual acuity remains relatively well preserved, GA often causes considerable compromise of visual function and quality of life. No treatment currently exists. We evaluated the safety and efficacy of pegcetacoplan (APL-2), a complement C3 inhibitor, for the treatment of GA. Design Prospective, multicenter, randomized, sham-controlled phase 2 study. Subjects 246 subjects with GA. Methods Subjects with GA were randomly assigned in a 2:2:1:1 ratio to receive intravitreal injections of 15 mg pegcetacoplan monthly or every-other-month (EOM) or sham intravitreal injections monthly or EOM, for 12 months with follow-up at months 15 and 18. Area and growth of GA were measured using fundus autofluorescence imaging. Main outcome measures The primary efficacy endpoint was mean change in square root GA lesion area from baseline to month 12. Secondary outcome measures included mean change from baseline in GA lesion area without the square root transformation, distance of GA lesion from the fovea (foveal encroachment), best corrected visual acuity (BCVA), low luminance BCVA (LL-BCVA), and low luminance visual acuity deficit (LL-VD). The primary safety endpoint was the number and severity of treatment emergent adverse events. Results In subjects receiving pegcetacoplan monthly or EOM, the GA growth rate was reduced by 29% (95% CI, 9 to 49; p=0·008) and 20% (95% CI, 0 to 40; p=0.067) compared with sham. Post-hoc analysis showed that the effect was greater in the second 6 months of treatment, with observed reductions of 45% (p=0.0004) and 33% (p=0.009) for pegcetacoplan monthly and EOM, respectively. Two cases of culture-positive endophthalmitis and one case of culture negative endophthalmitis occurred in the pegcetacoplan monthly group. New onset investigator-determined exudative AMD was reported more frequently in pegcetacoplan-treated eyes (18/86 eyes, or 20.9%, and 7/79 eyes, or 8.9%, in monthly and EOM groups, respectively) than in sham-treated eyes (1/81 eyes, or 1.2%). Conclusion Local inhibition of C3 with pegcetacoplan resulted in statistically significant reductions in the growth of GA compared with sham. Phase 3 study will further define the efficacy and safety profile.

Background Vaginal bleeding (VB) is common in women with gynecologic (GYN) malignancies. Radiation therapy (RT) is used for the definitive treatment of GYN cancers and palliation of bleeding. The historical dogma is that high dose-per-fraction radiation leads to more rapid bleeding cessation, yet there is scant data supporting this claim. We sought to examine the effect of RT fraction size on VB via retrospective analysis of patients receiving hypofractionated radiation (HFRT) compared to conventionally fractionated radiation (CFRT) for control of bleeding secondary to GYN malignancies. Methods We identified patients receiving external beam RT for continuous VB from GYN malignancy treated in our department from 2012 to 2020. RT was classified as HFRT (> 2.0 Gy/fx) or CFRT (1.8–2.0 Gy/fx). Demographic information, disease characteristics, and treatment details were collected. The primary endpoint was days from RT initiation until bleeding resolution. Characteristics between groups were compared via Fisher’s exact test. Time to bleeding cessation was assessed via Kaplan–Meier and log-rank test. Univariable and multivariable Cox-proportional hazards were used to identify factors associated with bleeding cessation. Results We identified 43 patients meeting inclusion criteria with 26 and 17 patients receiving CFRT and HFRT, respectively. Comparison of baseline characteristics revealed patients receiving HFRT were older (p = 0.001), more likely to be post-menopausal (p = 0.002), and less likely to receive concurrent chemotherapy (p = 0.004). Time to bleeding cessation was significantly shorter for patients receiving HFRT (log-rank p p = 0.008). Conclusions Patients with continuous VB from GYN tumors receiving HFRT experienced more rapid bleeding cessation than those receiving CFRT. For patients with severe VB, initiation of HFRT to control malignancy related bleeding quickly may be warranted.

Purpose This study aimed to report the early toxicity results of a prospective clinical trial of prostate stereotactic body radiation therapy (SBRT) to the entire prostate with a simultaneous integrated boost (SIB) to magnetic resonance imaging (MRI)-defined focal lesions. Methods and materials Eligible patients included men with biopsy-proven prostate stage T1c to T2c adenocarcinoma, a Gleason score ≤7, and prostate-specific antigen values of ≤20 ng/mL, who had at least 1 focal lesion visible on MRI and a total prostate volume no greater than 120 cm3. SBRT consisted of a dose of 36.25 Gy to the entire prostate with an SIB of 40 Gy to the MRI-defined lesions, delivered in 5 fractions. The primary purpose of the study was to confirm the feasibility of treatment planning/delivery and to estimate the rate of urinary retention requiring placement of a Foley catheter within 90 days of treatment. This study was to be considered successful if urinary retention occurred in no more than 15% of cases, with a planned enrollment of at least 25 patients. Results A total of 26 men were enrolled, and all underwent SBRT as planned. Twenty patients (77%) had intermediate-risk features, and the remainder were low risk. A treatment plan that met the protocol-defined goals for all cases was developed. Two patients (7.7%) developed acute urinary symptoms that required the temporary placement of a Foley catheter. No grade 3+ toxicity events were observed. Conclusions Planning and delivery of prostate SBRT with a whole prostate dose of 36.25 Gy and a focal 40 Gy SIB is feasible. Early follow-up suggests that this treatment is not associated with undue morbidity.

The purpose of study is to measure Point A pear-shaped isodose dimensions of the conventional intracavitary brachytherapy with various sizes of colpostats and analyze which size of tumor is the optimal for 3-D interstitial brachytherapy. CT simulation was performed with Fletcher type applicator using various sizes of colpostats (2.0, 2.5, and 3.0 cm diameter). The Manchester standard loading (dwell time) system was used to generate pear-shaped isodose envelopes with high-dose rate iridium-192 according to the colpostat sizes. The size of the pear-shaped envelope was measured at 5 different levels: A-level (center of the colpostats), B-level (top of the colpostats), C-level (between B and D), D-level (Point A), and E-level (1.0 cm above Point A). In this study, it was assumed that uterine tandem was located at the center of tumor. For width of pear-shape: At the A-level, 6.4, 7.3, and 8.0 cm for 2.0, 2.5, and 3.0 cm colpostats, respectively. At the B-level, 5.8, 6.4, and 6.8 cm for 2, 2.5, and 3.0 cm colpostats, respectively. At the C-level, 4.6, 4.8, and 4.8 for 2.0, 2.5, and 3.0 cm colpostats, respectively. At the D-level, 4.0 cm for all different size. At the E-level, 3.8 cm for all 3 different size colpostats. A-level was the largest dimension of pear-shape. However, it was located in the upper vagina below the main cervical mass. The center of the effective pear-shape size for tumor was between the C and D levels. For thickness, all 5 different levels were ranging 3.7 to 4.0 cm. For height, the length of height was dependent on the tandem length. Therefore, the pear-shape envelope was able to accommodate up to 4.0 cm diameter volume. According to our analysis of conventional pear-shape dimension, 3-D interstitial brachytherapy should be considered for tumors larger than 4.0 cm for symmetrical tumor.

This study aimed to investigate the dynamics of the vaginal wall dose for interstitial brachytherapy (ISBT). A patient undergoing ISBT was selected as the patient case. The phantom case was generated to simulate the patient case in all regards with the exception of parallel needle positions. The vaginal wall was contoured as a 0.5-cm expansion around the vaginal surface of the obturator. The prescribed ISBT dose was 20 Gy in 4 fractions. Six treatment plans were generated by modifying relative dwell times and needle positions (DTNP). The volume of the vaginal wall receiving > 150% of prescription dose (V > 150% ) and D 2cc of the vaginal wall were compared among plans. The V > 150% was much larger in the patient case (49.3%) due to unparallel needles compared with the phantom case (14.3%) without modification (plan 1). Among the 6 plans, reduced dwell time (plan 3) and no dwell time (plans 5 and 6) on the vaginal surface needles had the lowest vaginal wall doses with the use of a central obturator needle in both cases. In comparison of patient case plans 1, 3, 5, and 6, V 150% was 49.2%, 19.0%, 21.3%, and 28.7%, respectively, and D 2cc was 41.15 Gy, 33.10 Gy, 36.51 Gy, and 34.37 Gy, respectively, which was limited around each loaded needle. Modification of DTNP is able to reduce the vaginal wall volume exceeding 150% of the prescription dose in the patient case. Understanding these dynamics of the vaginal wall dose will improve dose optimization of ISBT and may reduce vaginal morbidities.

PURPOSE/OBJECTIVE(S) Stereotactic Body Radiation Therapy (SBRT) is increasingly utilized as a definitive treatment option for patients with prostate adenocarcinoma, especially in the low or intermediate risk setting. The aim of this study is to assess the late toxicity and biochemical recurrence rates of a single institution prospective clinical trial evaluating prostate SBRT with simultaneous integrated boost (SIB) targeting focal lesions as defined by magnetic resonance imaging (MRI). MATERIALS/METHODS Patients were eligible if they had biopsy-proven low or intermediate risk prostate adenocarcinoma with initial prostate specific antigen (PSA) values ≤20 ng/mL, clinical stage from T1c to T2c, and Gleason score ≤7. Patients also had to have one or more focal lesions on MRI and an MRI-defined total prostate volume of < 120 cm3. All patients received SBRT delivered to the entire prostate to a dose of 36.25 Gy in 5 fractions with an SIB to the lesions seen on MRI to 40 Gy in 5 fractions. Late toxicity was defined as any possible treatment-related adverse event occurring after three months from the completion of SBRT and graded according to the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0). Biochemical recurrence was defined by the Phoenix definition of PSA increase of 2 ng/mL above the nadir. RESULTS A total of 26 patients were enrolled, and all enrolled patients underwent planned SBRT. Six patients (23.1%) had low risk disease and twenty patients had intermediate risk disease (76.9%). Eight patients (30.8%) received androgen deprivation therapy. Median follow up was 40.5 months (range 12-64 months). No biochemical failures have yet been observed. Three patients (11.5%) experienced late grade 2 genitourinary (GU) toxicity requiring cystoscopy; two of these three patients experienced hematuria requiring cystoscopy and one patient experienced dysuria requiring cystoscopy. Six patients (23.1%) had late grade 2 GU toxicity requiring medications such as tamsulosin or oxybutynin. Two patients (7.7%) had late grade 2 gastrointestinal (GI) toxicity; both patients experienced hematochezia requiring colonoscopy and were found to have proctitis requiring steroids per rectum. There was no grade 3 or higher toxicity events observed. CONCLUSION The results of this study support that SBRT to the entire prostate to a dose of 36.25 Gy in 5 fractions with focal SIB to 40 Gy in 5 fractions is not associated with undue late GI or GU toxicity. Thus far, this regimen has excellent biochemical control. Focal dose escalation with an SIB planning approach may be an opportunity to improve biochemical control while limiting dose to nearby organs at risk.

Aim To report outcomes for patients with para-aortic lymph node positive cervical cancer treated with a dynamic field-matching technique. Background PET staging of cervical cancer has increased identification of patients with para-aortic lymph node metastasis. IMRT enables dose escalation in this area, but matching IMRT fields with traditional whole pelvis fields presents a challenge. Materials and methods From 2003 to 2012, 20 patients with cervical cancer and para-aortic lymph node metastasis were treated utilizing the dynamic field-matching technique. As opposed to single-isocenter half-beam junction techniques, this technique employs wedge-shaped dose junctions for the abutment of fields. We reviewed the records of all patients who completed treatment with the technique and abstracted treatment, toxicity, and disease-related outcome data for analysis. Results Median prescribed dose to the whole pelvis field was 45 Gy and para-aortic IMRT field 50.4 Gy. All but 3 patients underwent HDR (13 pts) or LDR (4 pts) brachytherapy. All patients developed lower GI toxicity; 10 grade 1, 9 grade 2, and 1 grade 4 (enterovaginal fistula). Median DFS was 12.4 months with 1 and 2-year DFS 60.0% and 38.1%. One-year OS was 83.7% and 2-year OS, 64.4%. A total of 10 patients developed recurrence; none occurred at the matched junction. Conclusions The dynamic field-matching technique provides a means for joining conventional whole pelvis fields and para-aortic IMRT fields that substantially reduces dose deviations at the junction due to field mismatch. Treatment with the dynamic matching technique is simple, effective, and tolerated with no apparent increase in toxicity.

Whole pelvic radiation therapy (WPRT) is an integral part of treatment for locally advanced cervical and vaginal cancer prior to brachytherapy. The most common beam arrangements for WPRT are opposed anteroposterior/ posteroanterior beams and the 4-field box. The lateral fields of the 4-field box spare small bowel and a portion of the rectum from radiation. Intensity modulated radiation therapy (IMRT) is increasingly used for gynecologic (GYN) cancers to improve dose conformity. Before the availability of computed tomography (CT), the portals used for WPRTwere determined solely based on bony anatomy. Because fluoroscopy-based planning risks geometric miss,1,2 CT-based planning is now considered standard. Conventional WPRT portals are designed to include the primary tumor, uterus, upper vagina, and regional lymphatics (common, external and internal iliac, and presacral lymph nodes). However, the mesorectum is not consistently contoured as a target volume. The advent of fluorine-18 fludeoxyglucose (FDG) positron emission tomography (PET)/CT scan has increased

To investigate the effect of hypofractionated external beam radiation therapy (RT) on sexual function in patients treated for localized prostate cancer, and also to determine the effect of radiation dose to the penile bulb or crura of the corpus cavernosum on sexual function outcome.Forty-one patients treated with hypofractionated RT without androgen deprivation were prescribed 67.6-70.2 Gy to the prostate, delivered in 26-28 fractions. The primary endpoint was erectile dysfunction (ED) category based on the Sexual Health Inventory for Men (SHIM) score closest to 2 years from RT. The penile bulb and crura were contoured and mean radiation dose calculated for each structure.The mean pretreatment SHIM score was 19.8, and the mean posttreatment SHIM score was 15.1. The ED category was decreased by ≥ 2 in 50% of patients with a mean penile bulb of20 Gy compared with that in 9% of patients with a mean penile bulb dose of ≤ 20 Gy (P = .003). Mean dose to the crura was highly correlated with mean dose to the penile bulb (Pearson correlation = 0.842; P.001) but did not reach statistical significance as a predictor of ED after radiation.Radiation dose to the penile bulb is predictive of posttreatment ED in patients treated with dose-escalated hypofractionated prostate RT. The cutpoint at which this effect was observed with this treatment is substantially lower than the previous reports.

Purpose To analyze the D2 cc hot spot in three-dimensional CT and anatomic factors affecting the D2 cc hot spot in organs at risk (OARs). Methods and Materials Thirty-one patients underwent pelvic CT scan after insertion of the applicator. High-dose-rate treatment planning was performed with standard loading patterns. The D2 cc structures in OARs were generated in three dimensional if the total equivalent dose in 2 Gy exceeded our defined dose limits (hot spot). The location of D2 cc hot spot was defined as the center of the largest D2 cc fragment. The relationship between the hot spot and the applicator position was reported in Digital Imaging and Communication in Medicine coordinates. Results The location of sigmoid, small bowel, and bladder D2 cc hot spots was around the endocervix: The mean location of sigmoid hot spot for lateral view was 1.6 cm posteriorly and 2.3 cm superiorly (Y, 1.6 and Z, 2.3), small bowel was 1.6 cm anteriorly and 2.7 cm superiorly (Y, −1.6 and Z, 2.7). The mean location of bladder hot spot was 1.6 cm anteriorly and 1.6 cm superiorly (Y, −1.6 and Z, 1.6). These hot spots were near the plane of Point A (X, 2.0 or −2.0; Y, 0; and Z, 2.0). The mean location of rectal hot spot was 1.6 cm posteriorly and 1.9 cm inferiorly (Y, 1.6 and Z, −1.9). D2 cc hot spot was affected by uterine wall thickness, uterine tandem position, fibroids, bladder fullness, bowel gas, and vaginal packing. Conclusions Because of the location of the D2 cc hot spots, larger tumors present a challenge for adequate tumor coverage with a conventional brachytherapy applicator without an interstitial implant. Additionally, anatomic factors were identified which affect the D2 cc hot spot in OARs.

Aims To evaluate pazopanib eye drops in patients with subfoveal choroidal neovascularisation secondary to age-related macular degeneration. Methods 70 patients with minimally classic or occult subfoveal choroidal neovascularisation were randomly assigned to 5 mg/mL TID, 2 mg/mL TID, and 5 mg/mL QD pazopanib eye drops for 28 days in a multicentre, double-masked trial with an optional safety extension for up to 5 additional months. The primary outcomes were central retinal thickness (CRT) and best-corrected visual acuity (BCVA) at Day 29. Results No significant decrease from baseline in CRT was observed overall; however, an exploratory analysis showed improvement in CRT (mean decrease of 89 μm) in patients with the CFH TT genotype who received 5 mg/mL TID (p=0.01, n=5). Mean increases in BCVA were observed in the 5 mg/mL TID overall (4.32 letters (p=0.002, n=26)) and in those that with CFH Y402H TT (6.96 letters (p=0.02, n=5)) and CT (4.09 letters (p=0.05, n=9)) genotypes. No safety signals that precluded continued investigation were detected. Conclusions 5 mg/mL pazopanib eye drops resulted in mean improvement in BCVA at Day 29 and improvements in vision. However, improvement in macular oedema for age-related macular degeneration was found only in the subset of subjects with the CFH Y402H TT genotype, warranting further investigation.

To determine if high-risk prostate cancer responds differently to hypofractionation.One hundred and fifty-seven men with NCCN high-risk (T3, PSA20, or Gleason ≥ 8) clinically localized prostate cancer treated between 1998 and 2010 met the inclusion criteria for the analysis. Eighty-two were treated with conventional WPRT with a conventionally fractionated sequential boost to the prostate (cRT), with the prostate receiving 75-77 Gy in 1.8-2.0 Gy fractions. Seventy-five were treated with pelvic IMRT with a hypofractionated simultaneous boost to the prostate (hRT), with the prostate receiving 70 Gy in 2.5 Gy fractions. The dose to the pelvic lymph nodes was 45 Gy in the cRT group and 50.4 Gy in the hRT group, both at 1.8 Gy per fraction. Ninety-two percent received neoadjuvant hormonal ablation therapy, typically beginning two months prior to the start of RT.Median follow-up was 6.5 years for men receiving cRT and 3.7 years for those receiving hRT. The actuarial rate of biochemical control at four years was 88% for cRT and 94% for hRT (p = 0.82). The rates of early rectal and urinary grade ≥ 2 toxicities were 35% (29 of 82) and 49% (40 of 82) for the cRT group and 36% (27 of 75) and 44% (33 of 75) for the hRT group. The actuarial rate of late grade ≥ 2 rectal toxicity at four years was 25% for the cRT group and 13% for the hRT group (p = 0.037). The rate of late grade 3 rectal complications was 4% (3 of 82) for patients receiving cRT and 1% (1 of 75) for patients receiving hRT.Initial follow-up indicates equivalent biochemical control between regimens. Patients receiving hRT experienced fewer late rectal complications.

ObjectiveThe objective of this study was to evaluate the University of Alabama at Birmingham experience with routine intraoperative ultrasound (IUS)–guided tandem placement for cervical cancer.MethodsBetween 1999 and 2008, 243 cervical cancer patients underwent IUS-guided tandem placement. One hundred thirty-nine patients received low-dose-rate brachytherapy, and 104 received high-dose-rate brachytherapy. Three hundred fifty-six IUS-guided procedures were performed. Clinical and imaging data were retrospectively analyzed to evaluate complications requiring reinsertion of tandem placement in the context of IUS.ResultsAll 243 cervical cancer patients completed intracavitary brachytherapy. Five (1.4%) of 356 IUS-guided applicator placements resulted in uterine perforation. All of these patients underwent successful tandem insertion on the second attempt, and no significant clinical sequelae occurred. Intraoperative ultrasound enabled direct uterine visualization and facilitated real-time feedback for selection of a suitable tandem length and curvature; no suboptimal placements requiring return to the operating room occurred (excluding perforation).ConclusionsIn this large series, IUS guidance substantially increased the rate of successful applicator placement and diminished the rate of uterine perforation relative to historical controls. We strongly recommend the use of IUS guidance during operative intrauterine tandem placement for cervical cancer.

The prevalence of overweight (body mass index [BMI] N 25 kg/m2) and obesity (BMI N30 kg/m2) in the United States currently exceeds two-thirds of the adult population. Obesity and severe obesity (BMI N 40 kg/m2) may impact the management of early-stage cervical cancer, where surgical resection is often the preferred treatment.1 Due to medical comorbidities and surgical risks, these patients are often not considered surgical candidates, and definitive radiation or chemoradiation may be the only curative option. Although most patients with inoperable cervical cancer are physically able to undergo a computed tomographic (CT) simulation and subsequent radiation treatment, patients with severe obesity and large abdominopelvic girth may present obstacles in simulation, treatment planning and dosimetry, and treatment delivery. Potential clinical problems include weight in excess of simulator or treatment table limits, girth in excess of CT bore or field of view,2 poor image quality secondary to tissue attenuation, creating an accurate body contour, achieving an acceptable dose distribution and heterogeneity index given the confines of beam arrangement and body thickness, gantry clearance issues, issues with patient setup and verification, and reliability of external fiducials. In this study, we report

Purpose To investigate the dosimetric effects of bladder filling on organs at risk (OARs) using three-dimensional image-based treatment planning for vaginal cylinder brachytherapy. Methods and Materials Twelve patients with endometrial or cervical cancer underwent postoperative high–dose rate vaginal cylinder brachytherapy. For three-dimensional planning, patients were simulated by computed tomography with an indwelling catheter in place (empty bladder) and with 180 mL of sterile water instilled into the bladder (full bladder). The bladder, rectum, sigmoid, and small bowel (OARs) were contoured, and a prescription dose was generated for 10 to 35 Gy in 2 to 5 fractions at the surface or at 5 mm depth. For each OAR, the volume dose was defined by use of two different criteria: the minimum dose value in a 2.0-cc volume receiving the highest dose (D 2cc ) and the dose received by 50% of the OAR volume (D 50% ). International Commission on Radiation Units & Measurements (ICRU) bladder and rectum point doses were calculated for comparison. The cylinder-to-bowel distance was measured using the shortest distance from the cylinder apex to the contoured sigmoid or small bowel. Statistical analyses were performed with paired t tests. Results Mean bladder and rectum D 2cc values were lower than their respective ICRU doses. However, differences between D 2cc and ICRU doses were small. Empty vs. full bladder did not significantly affect the mean cylinder-to-bowel distance (0.72 vs. 0.92 cm, p = 0.08). In contrast, bladder distention had appreciable effects on bladder and small bowel volume dosimetry. With a full bladder, the mean small bowel D 2cc significantly decreased from 677 to 408 cGy ( p = 0.004); the mean bladder D 2cc did not increase significantly (1,179 cGy vs. 1,246 cGy, p = 0.11). Bladder distention decreased the mean D 50% for both the bladder (441 vs. 279 cGy, p = 0.001) and the small bowel (168 vs. 132 cGy, p = 0.001). Rectum and sigmoid volume doses were not affected by bladder filling. Conclusions In high–dose rate vaginal cylinder brachytherapy, treatment with a distended bladder preferentially reduces high dose to the small bowel around the vaginal cuff without a significant change in dose to the bladder, rectum, or sigmoid.

ObjectiveTo evaluate the incidence and risk factors for mesorectal node metastasis (MRNM) in locally advanced cervical cancer.Methods/MaterialsWe performed an observational retrospective cohort study of 122 patients with cervical cancer who received definitive chemo-radiation treatment between December 2013 and June 2017 to evaluate the incidence of MRNM. Three diagnostic radiologists assessed all available pre-treatment images. In this study, the pelvic node metastasis was defined as ≥ 1.0 cm and MRNM as ≥ 0.5 cm for CT and MRI scans and as a maximum standardized uptake value of > 2.5 for PET/CT. The relationship of MRNM with FIGO stage, pelvic node metastasis, and mesorectal fascia involvement was evaluated.ResultsThe incidence of MRNM in all 122 patients was 8 (6.6%). However, in advanced stage (III– IV) patients, MRNM occurred in 4 of 39 (10.3%) compared with 4 of 83 (4.8%) in early stage (IB1–IIB) patients (p = 0.27). In patients with a positive pelvic node, MRNM occurred in 7 of 55 (12.7%) and 1 of 67 (1.5%) in those with negative pelvic node (p = 0.02). In addition, the incidence of MRNM was 3 of 9 (33.3%) in the presence of mesorectal fascia involvement and 5 of 113 (4.4%) among those without mesorectal fascia involvement (p = 0.013).ConclusionThis study indicates that pelvic node metastasis and mesorectal fascia involvement are high-risk factors for MRNM. Therefore, vigilance of reviewing images in the mesorectum for MRNM is necessary for high-risk patients.

To investigate the feasibility of combining conventional high-dose-rate (HDR) brachytherapy with a concomitant complementary intensity-modulated radiotherapy (IMRT) boost for improved target coverage in cervical cancers.Six patients with cervical cancer underwent conventional HDR (C-HDR) treatment. Computed tomography (CT) and magnetic resonance imaging (MRI) scans were acquired with a CT/MRI-compatible applicator in place. The clinical target volumes (CTVs), defined as the gross target volume with a 3-mm margin and the uterus, were delineated on the CT scans, along with the organs at risk (OARs). The IMRT plans were optimized to generate dose distributions complementing those of C-HDR to cover the CTV while maintaining low doses to the OARs (IMRT-HDR). For comparison, dwell-weight optimized HDR (O-HDR) plans were also generated to cover the CTV and spare the OARs. The three treatment techniques (C-HDR, O-HDR, and IMRT-HDR) were compared. The percentage of volume receiving 95% of the prescription dose (V(95)) was used to evaluate dose coverage to the CTV, and the minimal doses in the 2.0-cm(3) volume receiving the greatest dose were calculated to compare the doses to the OARs.The C-HDR technique provided very poor CTV coverage in 5 cases (V(95)62%). Although O-HDR provided excellent gross tumor volume coverage (V(95)or =96.9%), it resulted in unacceptably high doses to the OARs in all 6 cases and unsatisfactory coverage to the whole CTV in 3 cases. IMRT-HDR not only yielded substantially improved CTV coverage (average V(95) = 95.3%), but also kept the doses to the bladder and rectum reasonably low.Compared with C-HDR and O-HDR, concomitant IMRT boost complementary to C-HDR not only provided excellent CTV coverage, but also maintained reasonably low doses to the OARs.

Of the 423 patients enrolled, 94.3% of those given 0.3 mg of ranibizumab and 96.4% of those given 0.5 mg lost fewer than 15 letters, as compared with 64.3% of those in the verteporfin group (P

Purpose To review the clinical outcome retrospectively of cervical cancer patients treated definitively with either high-dose-rate (HDR) or low-dose-rate (LDR) brachytherapy. Methods and materials One hundred sixty patients (44 Stage I, 83 Stage II, and 33 Stage III) were treated from 1990 to 2000 with curative intent for carcinoma of the cervix. One hundred three LDR patients were compared to 57 HDR patients. Two groups were treated during the same period. An external beam dose of 45 Gy to the entire pelvis was delivered at 1.8 Gy per fraction to most patients before the first intracavitary insertion in both groups. Brachytherapy was delivered in one to two LDR implants or four to five HDR implants at 6 Gy per fraction. The prescribed dose to Point A for LDR was at least 80–85 Gy. Patient characteristics were similar for each cohort. Point A doses were similar for each stage. The primary endpoints assessed were survivals and failure sites. Endpoints were estimated using the Kaplan–Meier method and comparisons between treatment groups were performed using the log-rank test. Results The median followup was 48 months for the LDR group and 59 months for the HDR group. For all stages combined and stage for stage in both groups, there was no statistically significant difference in locoregional control, cause-specific survival, and overall survival for LDR compared with HDR. Locoregional control and overall survival were 78% and 60% for LDR compared to 76% and 55% for HDR at 3 years, respectively ( p = 0.96 and p = 0.48). Median cause-specific survival values for LDR vs. HDR were 71 and 81 months, respectively ( p = 0.62). The cause-specific survival for LDR patients was 62% compared with 59% for HDR patients at 3 years. For Stage IB2, II, and III LDR patients, cause-specific survival rates were 62%, 67%, and 45%, compared to 67%, 57%, and 33% for HDR at 3 years, respectively ( p = 0.75, p = 0.95, and p = 0.48). For patients with a recorded site of first failure, the most common site was locoregional (56%) and then distant metastases (26%). Eight patients who were cancer free developed late complications requiring surgical intervention. Two patients were in the HDR group (3.5%) and 5 in the LDR group (4.8%). Conclusions Similar outcome was observed for LDR compared with HDR intracavitary brachytherapy for the entire cohort. In this review, HDR group was not inferior to LDR group in advanced stages. This is likely because our patients were treated with brachytherapy after a high dose of external pelvic radiotherapy in both LDR and HDR patients.

Purpose With advances in imaging studies, dose specification for uterine cancer can be defined at specific anatomical sites such as the myometrium or the serosal surface rather than at arbitrary points or milligram-hours. This report presents our experience with image-based brachytherapy for inoperable uterine cancer. Methods and materials Eight patients with organ-confined uterine cancer (2 Stage I GI, 3 Stage I G2, 3 Stage I G3) underwent definitive radiation therapy because of poor medical condition. All the patients underwent a CT or MRI scan of the pelvis before intracavitary application. Based on the size of the uterine cavity, a single-channel intrauterine applicator was selected for a small uterus, and a multiple-channel intrauterine applicator was used for a large uterus. A CT ( n =5) or MRI ( n =3) scan of the pelvis was performed with the applicator in place in addition to orthogonal pelvic films. Individualized dose specification was 75 Gy to the midmyometrium and limited to 50 Gy to the serosal surface of the uterus based on imaging information. Results Four patients with Stage I G1–2 disease had intracavitary brachytherapy alone. Four patients with Stage I G2–3 disease were treated with a combination of external pelvic radiation and intracavitary brachytherapy. Six patients had low-dose-rate brachytherapy, and 2 patients had high-dose-rate brachytherapy. Five patients had single-channel intrauterine brachytherapy, and 3 patients had multiple-channel brachytherapy. Based on the measurements of the uterine wall thickness by the imaging studies, the dose specification was prescribed to 1.5 cm lateral to the central axis of the uterus in 4 patients, 2.0 cm in 3 patients, and 2.5 cm in 1 patient. The medium followup time after radiation treatment was 38 months. Six patients are alive without evidence of disease, and 2 patients died of other causes. All patients had local control without major side effects. Conclusions Image-based brachytherapy based on individualized dose specification at specific anatomical sites can be done easily and provides excellent local control for inoperable uterine cancer.

Purpose To evaluate the feasibility of dose-escalated para-aortic lymph node (PALN) intensity modulated radiation therapy (IMRT) in reducing the dose to bone marrow, bowel, spinal cord, and kidneys, compared with conventional radiation techniques of PALNs in patients with locally advanced cervical cancer and PALN metastases. Methods and materials Computed tomography scans and MRI studies of 5 cervical cancer patients with PALN involvement were transferred to an IMRT treatment planning workstation (Eclipse/Helios) for image fusion and definition of target volumes and critical structures. The positive PALNs identified on fused computed tomography–magnetic resonance images were defined as the gross target volume (GTV), and the PALN region was defined as the planning target volume. There were 2 distinct treatment regions: the PALN region superior to the isocenter and the whole-pelvis region inferior to the isocenter. Three treatment planning techniques were compared: AP/PA (both regions), 4-field box (both regions), and PALN-IMRT with 4-field box to the whole-pelvis field. With IMRT, the radiation dose to the GTV was escalated from the conventional 45 Gy to 60 Gy (2.4 Gy/fraction), whereas the planning target volume and whole-pelvis region received 45 Gy. The treatment planning isocenter was placed at the L4–L5 vertebral body interspace, and this allowed the two treatment regions to be abutted using independent jaws. Results This study has demonstrated the feasibility of escalating the dose delivered to grossly positive PALNs to 60 Gy (2.4 Gy/fraction) with a 95.6% median GTV coverage, concomitantly with conventional treatment of the whole-pelvis region. PALN-IMRT significantly reduced V 40 bone marrow compared to the AP/PA and 4-field box techniques with a median of 21.3%, 98%, and 49.7%, respectively. The PALN-IMRT and 4-field box techniques showed a reduction in V 45 bowel over the AP/PA technique, but a level of statistical significance was not reached. The spinal cord received a significantly higher maximum dose when PALNs were treated with AP/PA fields. Alternatively, the use of the 4-field box technique yielded a significant increase in V 22 kidney on both sides. The placement of the treatment planning isocenter at the L4–L5 interspace allowed the PALN-IMRT and whole-pelvis regions to be treated with a relatively uniform dose at the abutment region. Conclusion In this dosimetric analysis, we demonstrated that dose-escalated PALN-IMRT with conventional whole-pelvis radiotherapy is feasible with significant sparing of critical normal structures compared to PALN conventional radiation techniques.

Carcinoma of the cervix is typically treated with a combination of intracavitary brachytherapy and external beam radiation. The external beam dose is delivered with whole pelvis fields followed by split fields that protect midline organs at risk (bladder and rectum) while treating the parametria. Three approaches have been developed to shield midline structures: a simple rectangular block, a block customized to a single brachytherapy isodose line, and a step wedge filter constructed to conform to multiple brachytherapy isodose lines. A customized step wedge filter has the potential to produce a more homogeneous dose distribution but has not achieved widespread use due to labor intensive construction. We have developed a simple, novel method to produce a custom midline step wedge using dynamic multileaf collimation (dMLC). A comparison of film measurements in a phantom with the dose calculated by a commercial treatment planning system demonstrated agreement within 3% or 3 mm. The technique requires delivery times comparable to conventional techniques.

Purpose To investigate the relationship between the bulb of the penis and the peak of the urethrogram, and to compare this measurement with the ischial tuberosities (ITs) to peak distance. Methods and materials Pelvic CT scans from 50 consecutive patients with localized prostate cancer were analyzed to identify the penile bulb. Each patient was required to undergo retrograde urethrography during CT-based treatment planning with 3-mm slices. The peak of the urethrogram was defined as the last CT slice in which the contrast dye in the urethra could be visualized. Measurements were taken from the slice containing the most superior aspect of the penile bulb to the last slice of the urethrogram peak. The superior aspect of the penile bulb was defined as the CT slice nearest the peak that contained a bulbous structure at the base of the penis. This distance was defined as the bulb–peak distance. Similarly, the IT–peak distance was recorded for comparison. Results The mean bulb–peak and IT–peak distances were calculated for 47 of 50 patients. The peak of the urethrogram was unable to be evaluated in 3 patients. The mean, median, and range bulb–peak distance was 2.4 mm (SD 1.8), 3 mm, and 0–6 mm, respectively. The mean, median, and range IT–peak distance was 20.1 mm (SD 6.6), 21 mm, and 6–33 mm, respectively. No patient had the bulb located above the apex of the urethrogram. Conclusion The bulb of the penis is a relatively consistent soft-tissue landmark compared with the ITs and is located an average of 3 mm below the peak of the urethrogram. Therefore, the bulb of the penis is another landmark for the identification of the prostatic apex and is less invasive than retrograde urethrography.

Hemobilia is a rare manifestation of hepatic malignancies. The current treatment of choice for hemobilia is transcatheter hepatic arterial embolization. However, there have been only two published reports that describe the use of hepatic arterial embolization for hemobilia caused by hepatic neoplasms. In addition, this procedure is occasionally unsuccessful in the treatment of hemobilia. A case in which hemobilia caused by hepatocellular carcinoma was successfully treated with percutaneous radiofrequency tumor ablation after several failed hepatic arterial embolizations is described in this report.

Purpose/objective(s) To assess subcutaneous adipose tissue characteristics by computed tomography (CT) as potential imaging biomarkers predictive of biochemical recurrence in men with high-risk prostate cancer receiving radiotherapy (RT). Materials and methods This retrospective study included men with high-risk prostate cancer (PSA>20 ng/ml, Gleason score ≥8, or clinical extraprostatic extension) treated between 2001 and 2012. All patients received definitive, dose-escalated external beam RT along with a course of neoadjuvant, concurrent, and adjuvant androgen deprivation therapy (ADT). Each patient also had a treatment planning CT that included the L4-L5 vertebral interface and prostate specific antigen (PSA) measurements for at least 2 years following RT. The subcutaneous adipose tissue was contoured on a single axial CT slice at the level of L4-L5. The average CT attenuation, in Hounsfield units (HU), of the structure was calculated and defined as SAT HU . SAT AREA was defined as the cross-sectional area of the structure (in cm 2 ) that was then normalized by the square of patient height. Biochemical failure (BF) was defined as a PSA rise of 2 ng/ml from the nadir. Freedom from BF (FFBF) was calculated from start time of ADT using the Kaplan-Meier method. Estimates of FFBF were stratified by SAT HU and SAT AREA quartiles. Results A total of 171 men met the inclusion criteria with a median follow-up of 5.6 years. The mean SAT HU (±standard deviation) was −99.2 HU (±6.1 HU), and the mean SAT AREA was 93.2 cm 2 /m 2 (±39.4 cm 2 /m 2 ). The 5- and 8-year rates of FFBF across all patients were 81.5% and 73.5%, respectively. Patients in the lowest quartile of SAT HU experienced significantly higher FFBF compared to the other quartiles (Q4 vs. Q1, P = 0.017; Q4 vs. Q2, P = 0.045; Q4 vs. Q3, P = 0.044). No other differences in FFBF were observed between quartiles of SAT AREA or other quartiles of SAT HU . Conclusion Lower subcutaneous adipose tissue density was associated with a lower rate of BF following RT with ADT for men with high-risk prostate cancer. Further research is needed to elucidate the biological underpinnings of this clinical finding and the role adipose tissue plays in modulating oncologic behavior and outcomes.

Purpose: To investigate the dosimetric differences between colpostats and cylinder applicators for intrav- aginal brachytherapy. Methods and Materials: Dose distributions near vaginal colpostats and dome cylinders were computed with a commercial high-dose-rate treatment-planning system and verified by spot measurements by using LiF thermoluminescent dosimeters. Taking source anisotropy into account, dwell times were optimized by the computer by using the polynomial optimization on dose points method to give uniform doses along the lateral surfaces of the applicators. In addition, the effects of vaginal packing and the separation dis- tance between colpostats were studied by computing the dose to the vaginal mucosa, assuming 0.5 and 1.0 cm of vaginal packing and colpostat separation, respectively. Results: The computed and measured doses agreed within � 7%. Surface doses were similar for both types of applicators when the effect of shielding in the colpostats was neglected. However, percent depth doses in the anterior/posterior and lateral directions were higher for the cylinder, whereas the dose fall-off along the longitudinal patient axis was less pronounced for the colpostats. When vaginal packing at the anterior and posterior surface of the colpostats was increased from 0 to 5, 10, and 15 mm, the corresponding vagi- nal dose decreased from 97% of the prescription dose to 60%, 39%, and 26%, respectively. Separating the colpostats from 0 to 5 and 10 mm reduced the surface dose near the bladder/rectum to 80% and 67%, re- spectively, whereas the respective apex dose decreased from 105% of prescription to 91% and 77%. Conclusions: Colpostats and cylinder applicators for intracavitary brachytherapy have their advantages and disadvantages in depth dose distribution and clinical use. If treatment is confined to the vaginal apex, either applicator can be used. However, the colpostat separation should be kept to a minimum, and vaginal packing should be applied with great care to avoid generating cold spots along the upper vaginal surface and vaginal cuff. © 2002 Elsevier Science Inc. All rights reserved.

To determine if an abnormal CA-125 level in a menopausal female without ovarian cancer is associated with an increase in mortality.The Prostate, Lung, Colorectal, and Ovarian Cancer Screening Randomized Controlled (PLCO) Trial is a large multicenter prospective trial conducted by the National Cancer Institute (NCI). Over 78,000 healthy women aged 55-74 were randomized to a screening arm versus a usual medical care arm to evaluate the efficacy of screening in reducing mortality due to ovarian cancer. Women in the screening arm underwent annual screening for ovarian cancer with transvaginal ultrasound and CA-125 levels. There were 38,818 patients without ovarian cancer that had at least one CA-125 level drawn; 1201 (3.09%) had at least one abnormal level. The current study compares mortality in patients that had one or more abnormal CA-125 levels without ovarian cancer versus those with all normal levels.Patients with one or more abnormal CA-125 levels, without ovarian cancer, had a significantly higher mortality than patients with all normal CA-125 levels in the PLCO screening trial (p0.0001). This increased risk extended throughout the follow-up period. Analysis of cause of death listed on the death certificate showed an excess mortality attributable to lung cancer, digestive disease, and endocrine, nutritional, and metabolic disease.Menopausal females with an elevated CA-125 and without ovarian cancer are exposed to an increased risk of premature mortality.

Purpose: The purpose of this study was to evaluate the late toxicity and efficacy of twice-daily external irradiation to the pelvis and lumbar para-aortic region with brachytherapy and concurrent chemotherapy for carcinoma of the cervix with positive para-aortic lymph nodes. Patients and Methods: This study was designed to administer twice-daily radiation doses of 1.2 Gy to the pelvis and lumbar para-aortic lymph nodes (simultaneously) at 4–6-h intervals, 5 days per week. The total external radiation doses were 24–48 Gy to the whole pelvis, 12–36 Gy parametrial boost, and 48 Gy to the lumbar para-aortic region with an additional boost to a total dose 54–58 Gy to the positive para-aortic lymph node(s). One or two intracavitary implants were performed to deliver a minimum total dose of 85 Gy to point A. Cisplatin (75 mg/m 2 ; Days 1, 22, and 43) and 5-fluorouracil (1,000 mg/m 2 /24 h × 4 consecutive days, beginning on Days 1, 22, and 43) were given for two or three cycles. Results: Thirty patients with clinical Stages I–IV carcinoma of the cervix with biopsy-proven para-aortic lymph node metastases were enrolled in this study. Hyperfractionated external irradiation was completed in 87% (26 of 30). Brachytherapy was given in two implants to 47% (14 of 30) and in one implant to 33% (10 of 30); 13% (4 of 30) did not receive brachytherapy, 1 patient had three implants, and 1 had five high-dose-rate implants. Radiotherapy was completed per protocol in 70%. Three cycles of chemotherapy were given to 23% (7 of 30); 73% (22 of 30) received two cycles, and 1 patient did not receive chemotherapy. The acute toxicity from chemotherapy was Grade 1 in 3%, Grade 2 in 17%, Grade 3 in 48%, and Grade 4 in 28%. Acute toxicity from radiotherapy was Grade 1 in 7%, Grade 2 in 34%, Grade 3 in 21%, and Grade 4 in 28%. Late toxicity was Grade 1 in 10%, Grade 2 in 17%, Grade 3 in 7%, and Grade 4 in 17%. Grade 5 toxicity occurred in 1 patient during the course of therapy, but none had a late Grade 5 toxicity. The median follow-up time for the 7 patients alive at the time of last follow-up was 57 months. The overall survival estimates were 46% at 2 years and 29% at 4 years. The probability of local-regional failure was 40% at 1 year and 50% at 2 and 3 years. The probability of disease failure at any site was 46% at 1 year, 60% at 2 years, and 63% at 3 years. Conclusion: The results suggest that twice-daily external irradiation to the pelvis and lumbar para-aortic region with brachytherapy and concurrent chemotherapy resulted in an unacceptably high rate (17%, 5 of 29) of Grade 4 late toxicity. One patient died of acute complications of therapy. The survival estimates seem no better than standard fractionation irradiation without chemotherapy.

Although copper damascene interconnects offer many advantages over conventional subtractive etched Al alloys, the challenges and costs associated with converting to copper have combined to extend the useful life of Al alloy etching into the deep submicron regime. As a result, metal masking and etching are facing new challenges. Deep ultraviolet (DUV) photolithography has replaced the conventional i-line technique for patterning fine metal pitches, but some DUV photoresists are less able to withstand the aggressive plasma environment than their i-line counterparts. Reflectivity increases at DUV wavelength, so dielectric antireflective films are added on top of the metal stack. The mask-open process, where the dielectric film is plasma etched prior to etching the metal stack, alters the photoresist further and influences the subsequent metal etch. Aspect ratio dependent etch effects increase when etching narrow spaces resulting from tightened metal pitches, and gas additives may be required to protect the metal sidewalls. These effects are characterized and the challenges of deep submicron metal etch process development are discussed. The option of true hardmasked etching of the metal stack is also investigated.

Purpose: Preoperative and immediate postoperative irradiation of traumatic acetabular fractures (TAF), although known to reduce heterotopic ossification (HO), can cause significant organizational and logistic difficulties. We sought to determine an acceptable time interval between surgery and radiation without compromising control, as well as to update our large experience and to further validate our treatment philosophy. Methods and Materials: Beginning in June 1995, we began a prospective study, irradiating 152 patients on postoperative days 1, 2, or 3. There were also 17 patients delayed further secondary to medical difficulties. Results: All patients treated since June 1995 received 700 cGy/1 fx. Fifty-eight patients received radiation within 24 hours of surgery, 41 within 2 days, 53 within 3 days, 13 within 4 days, and 4 were delayed further. Delaying irradiation for up to 4 days postoperatively caused no statistical increase in HO ( p = 0.625). Of 263 patients in our retrospective cohort, HO occurred in 5.3% of patients who received irradiation versus 60% of patients who did not. Conclusion: In our prospective study, we noted no perceptible increase in HO with up to a 3-day interval between surgery and radiotherapy. This allows a more structured treatment schedule and allows the patient more time to heal and recover. Updated results from our overall series continue to demonstrate that adjuvant radiation decreases the incidence and severity of HO after TAF.

Stereotactic irradiation (radiosurgery) is a method of precisely focusing well-defined beams of radiation at small intracranial targets. The technique has been applied to the treatment of brain lesions that are benign (e.g., arteriovenous malformations, meningiomas, pituitary adenomas) and malignant (e.g., gliomas, metastases). This paper introduces preliminary data suggesting the possible value of radiosurgery in the management of ovarian cancer metastatic to the brain. Among 32 women with ovarian cancer metastatic to the brain treated with whole brain irradiation, nine (29%) experienced a complete radiographic response, compared with two of the five patients (40%) treated with radiosurgery. The 2-year survival rate was 60% among those treated with radiosurgery and 15% among those who received whole brain irradiation without radiosurgical boost. Stereotactic irradiation may be of clinical benefit to select patients with brain metastases resulting from ovarian cancer. A prospective randomized trial has been implemented by the Radiation Therapy Oncology Group (RTOG 95-08) to determine whether such observations are reproducible on a national scale.

Purpose: The purpose of this study was to evaluate the toxicity and efficacy of twice-daily external irradiation to the pelvis and para-aortics with brachytherapy and concurrent chemotherapy for carcinoma of the cervix with positive para-aortic lymph nodes. Methods and Materials: This study was designed to administer twice-daily radiation doses of 1.2 Gy to the pelvis and para-aortics at 4- to 6-h intervals, 5 days per week. The total external radiation doses were 24 to 48 Gy to the whole pelvis, 12 to 36 Gy parametrial boost, and 48 Gy to the para-aortics with an additional boost to a total dose of 54 to 58 Gy to the known metastatic para-aortic site. One or two intracavitary applications were performed to deliver a total minimum dose of 85 Gy to point A. Cisplatin (75 mg/m 2 , days 1 and 22) and 5-FU (1000 mg/m 2 /24 h × 4 days; days 1 and 22) were given for two or three cycles. Results: Twenty-nine patients with clinical Stages I to IV carcinoma of the cervix with biopsy-proven para-aortic lymph nodes were enrolled in this study. Hyperfractionated external radiotherapy was completed in 86% (25 of 29). Brachytherapy was given in two applications to 48% (14 of 29), 31% (9 of 29) had one intracavitary application, 14% (4 of 29) had no brachytherapy, one had three applications, and one had five HDR applications. Radiotherapy was completed per protocol in 69%. Three courses of chemotherapy were given to 24% (7 of 29), 72% (21 of 29) received two courses, and one patient did not receive chemotherapy. The acute toxicity from chemotherapy was Grade 1 in 3%, Grade 2 in 17%, Grade 3 in 48%, and Grade 4 in 28%. Radiotherapy toxicity was Grade 1 in 7%, Grade 2 in 34%, Grade 3 in 21%, and Grade 4 in 28%. One Grade 5 toxicity occurred and the patient died from a myocardial infarction from chemotherapy and radiotherapy colitis during her course of therapy. The median follow-up time was 18.9 months. The overall survival estimates were 59% at 1 year and 47% at 2 years. The probability of local-regional failure was 38% at 1 year and 49% at 2 years. The probability of disease failure at any site was 45% at 1 year and 59% at 2 years. Conclusion: The results suggest that twice-daily external irradiation to the pelvis and para-aortics with brachytherapy and concurrent chemotherapy resulted in an unacceptably high rate (31%, 9 of 29) of Grade 4 nonhematologic toxicity. One patient died from complications of therapy. Radiotherapy was completed per protocol in 69%. The survival estimates appear no better than standard fractionation radiotherapy without chemotherapy. Additional follow-up is necessary for long-term survival estimates.

Mutations in the gene encoding RDS/peripherin cause a variety of retinal disorders. Attempts to model such disorders in vitro and in vivo have been hampered by the paucity of available immunological reagents. Moreover, available antibodies have been generated from undefined or C-terminal epitopes and therefore may not suitable for detecting all known RDS/peripherin mutants. We consequently generated affinity-purified rabbit antibody against a 14 amino acid peptide corresponding to the highly conserved N-terminus of human RDS/ peripherin. This new antibody, N-RDS, recognizes RDS/peripherin in the retina of man, macaque, and rat. N-RDS may prove useful in studying RDS/peripherin mutants, particularly those with abnormal C-terminal domains.

Purpose To characterize retinal electrophysiologic and psychophysical abnormalities associated with membranoproliferative glomerulonephritis type II. Methods Three adults with membranoproliferative glomerulonephritis type II were studied. Retinal function was measured psychophysically (automated perimetry, Farnsworth D-15 color vision testing, and dark adaptometry) and electro-physiologically (full-field flash electroretinography and electro-oculography). Results Two symptomatic individuals had prominent drusenlike deposits and retinal pigment epithelial disturbances, findings characteristic of membranoproliferative glomerulonephritis type II retinopathy. These individuals had mild visual field and color vision abnormalities, prolonged dark adaptation, and delayed electroretinographic dark-adapted dim and bright flash responses of normal amplitude. The electro-oculogram of the most severely affected individual was abnormal. The third individual who was asymptomatic had the mildest fundus abnormalities and exhibited normal psychophysical and electrophysiologic responses. Conclusions Membranoproliferative glomerulonephritis type II retinopathy may be associated with symptomatic and measurable psychophysical and electrophysiologic abnormalities of retinal function.

Objective To examine medication safety in two intensive care units (ICU), and to assess the complexity of medication errors and adverse drug events (ADE) in ICUs across the stages of the medication-management process. Methods Four trained nurse data collectors gathered data on medication errors and ADEs between October 2006 and March 2007. Patient care documents (eg, medication order sheets, notes) and incident reports were used to identify medication errors and ADEs in a 24-bed adult medical/surgical ICU and an 18-bed cardiac ICU in a tertiary care, community teaching hospital. In this cross-sectional study, a total of 630 consecutive ICU patient admissions were assessed to produce data on the number, rates and types of potential and preventable ADEs across stages of the medication-management process. Results An average of 2.9 preventable or potential ADEs occurred in each admission, that is, 0.4 events per patient-day. Preventable or potential ADEs occurred in 2.6% of the medication orders. The rate of potential ADEs per 1000 patient-days was 276, whereas the rate of preventable ADEs per 1000 patient-days was 9.2. Most medication errors occur at the ordering (32%) and administration stages (39%). In 16–24% of potential and preventable ADEs, clusters of errors occurred either as a sequence of errors (eg, delay in medication dispensing leading to delay in medication administration) or grouped errors (eg, route and frequency errors in the order for a medication). Many of the sequences led to administration errors that were caused by errors earlier in the medication-management process. Conclusions Understanding the complexity of the vulnerabilities of the medication-management process is important to devise solutions to improve patient safety. Electronic health record technology with computerised physician order entry may be one step necessary to improve medication safety in ICUs. Solutions that target multiple stages of the medication-management process are necessary to address sequential errors.

Purpose. High-risk prostate cancer patients often receive radiotherapy (RT) to pelvic lymphatics (PLs). The aim of this study was to determine the safety margin around clinical target volume for PL (PL-CTV) to construct planning target volume for PL (PL-PTV) and for planning elective PL irradiation. Methods and Materials. Six patients who received RT to PL as part of prostate cancer treatment were identified. To determine average daily shifts of PL, the right and left IVs were contoured at 3 predetermined slices on the daily MV scans and their daily shifts were measured at these 3 levels using a measuring tool. Results. A total of 1,932 observations were made. Daily shifts of IV were random in distribution, and the largest observed shift was 13.6 mm in lateral and 15.4 mm in AP directions. The mean lateral and AP shifts of IV were 2.1 mm (±2.2) and 3.5 mm (±2.7), respectively. The data suggest that AP and lateral margins of 8.9 mm and 6.5 mm are necessary. Conclusions. With daily alignment to the prostate, we recommend an additional PL-CTV to PL-PTV conversion margin of 9 mm (AP) and 7 mm (lateral) to account for daily displacement of PL relative to the prostate.