Locoregional recurrence by molecular subtype after multicatheter interstitial accelerated partial breast irradiation: Results from the Pooled Registry Of Multicatheter Interstitial Sites research group.

PURPOSE: To determine in breast tumor recurrence (IBTR) and regional nodal recurrence (RNR) rates for women treated with multicatheter interstitial accelerated partial breast irradiation. METHODS AND MATERIALS: Data from five institutions were collected for patients treated from 1992 to 2013. We report outcomes of 582 breast cancers with ≥1 year of followup. Molecular subtype approximation was performed using estrogen receptor, progesterone receptor, Her2, and grade. The Kaplan-Meier method was used to calculate overall survival, IBTR, RNR, and distant recurrence rates. Univariate and multivariate Cox proportional hazard models were performed to estimate risks of IBTR and RNR. RESULTS: With a median followup time of 5.4 years, the 5-year IBTR rate was 4.7% overall, 3.5% for Luminal A, 4.1% for Luminal B, 5.2% for Luminal Her2, 13.3% for Her2, and 11.3% for triple-negative breast cancer. Positive surgical margins and high grade were associated with increased risk for IBTR, as was Her2 subtype in comparison with Luminal A subtype. Other individual subtypes comparisons did not show a significant difference. Analysis of Luminal A vs. all other subtypes demonstrated lower IBTR risk for Luminal A (5-year IBTR 3.5% vs. 7.3%, p = 0.02). The 5-year RNR rate was 2.1% overall, 0.3% for Luminal A, 4.6% for Luminal B, 2.6% for Luminal Her2, 34.5% for Her2, and 2.3% for triple-negative breast cancer. RNR risk was higher for women with Her2 compared to the other four subtypes and for Luminal B compared to Luminal A subtype. CONCLUSIONS: Molecular subtype influences IBTR and RNR rates in women treated with multicatheter interstitial accelerated partial breast irradiation.

Brachytherapy catheter spacing and stabilization technique.

PURPOSE/OBJECTIVES: To facilitate catheter spacing, implant stability, and patient comfort during multicatheter interstitial brachytherapy. METHODS AND MATERIALS: Uniform and consistent spacing of multiple interstitial implant catheters can be difficult because individual catheters may become displaced during the course of treatment. The authors have developed a brachytherapy catheter fixation method using Jackson-Pratt (JP) drains that can be used within wounds to maintain catheter spacing or on the skin surface for applicator fixation. JP drains are threaded over the implant needles to space and stabilize the implant geometry. The needles are then replaced with the usual brachytherapy catheters. RESULTS: Surgically directed ("open") placement of implant catheters is less prone to displacement when a drain connects and spaces the catheters in the wound. Fixation on the skin surface can also be achieved with the JP drains, which make the friction buttons optional. The soft drain material helps avoid discomfort and pressure injury sometimes associated with hard plastic buttons. Small (10 French) round JP drains are suitable for breast, and head and neck sites and larger 7×10-mm flat JP drains for extremity sarcomas, abdominal, or thoracic tumors. CONCLUSIONS: The complex brachytherapy devices fashioned from widely available surgical drains effectively guide and maintain geometry for multicatheter interstitial implants. Stable implant geometry leads to more reliable implementation of brachytherapy dosimetry. Patient comfort is improved and soft tissue injury from hard-edged buttons is avoided.

High dose brachytherapy as monotherapy for intermediate risk prostate cancer.

PURPOSE: We evaluated our retrospective, single institution experience with high dose rate brachytherapy as monotherapy for intermediate risk prostate cancer. MATERIALS AND METHODS: Our cohort included 284 patients with intermediate risk prostate cancer, defined as clinical stage T2b/T2c, Gleason score 7 and/or prostate specific antigen 10 to 20 ng/ml, and 1-year minimum followup. Treatment was 2 high dose rate brachytherapy sessions at 3 fractions of 6.5 Gy each for a mean of 19 days. Prostate specific antigen failure was defined as nadir +2 ng/ml. RESULTS: Mean followup was 35.1 months (median 31.9). Actuarial 5-year cause specific survival and clinical local control were 100%, distant-metastasis-free survival 98.8% and biochemical disease-free survival 94.4%. Clinical stage predicted biochemical disease-free survival. For stage T2a or less 5-year biochemical disease-free survival was 95.1% vs 100% for stage T2b and 77.4% for T2c (p = 0.012). Percent positive biopsy cores and prostate specific antigen nadir were also predictive. International Prostate Symptom Score results remained stable and potency was maintained in 82.6% of patients at 2 years. Pads were used for the first time after brachytherapy in 22 patients (7.7%), mostly for grade 1 incontinence (occasionally or less per week). Excluding patients with prior transurethral prostatectomy, stroke or tremor 2.5% used pads for the first time after treatment. No patient had urethral stricture. Radiation Therapy Oncology Group grade 1 rectal toxicity developed in 12 patients (4.2%) but not beyond grade 1. CONCLUSIONS: High dose rate brachytherapy as monotherapy is safe and effective for patients with intermediate risk prostate cancer. We recommend caution for percent positive biopsy cores exceeding 75% or clinical stage T2c. Excluding such patients the 5-year biochemical disease-free survival rate was 97.5%.

American Society for Radiation Oncology (ASTRO) and American College of Radiology (ACR) practice guideline for the performance of high-dose-rate brachytherapy.

High-Dose-Rate (HDR) brachytherapy is a safe and efficacious treatment option for patients with a variety of different malignancies. Careful adherence to established standards has been shown to improve the likelihood of procedural success and reduce the incidence of treatment-related morbidity. A collaborative effort of the American College of Radiology (ACR) and American Society for Therapeutic Radiation Oncology (ASTRO) has produced a practice guideline for HDR brachytherapy. The guideline defines the qualifications and responsibilities of all the involved personnel, including the radiation oncologist, physicist and dosimetrists. Review of the leading indications for HDR brachytherapy in the management of gynecologic, thoracic, gastrointestinal, breast, urologic, head and neck, and soft tissue tumors is presented. Logistics with respect to the brachytherapy implant procedures and attention to radiation safety procedures and documentation are presented. Adherence to these practice guidelines can be part of ensuring quality and safety in a successful HDR brachytherapy program.

Planned neck dissection after definitive radiotherapy or chemoradiation for base of tongue cancers.

OBJECTIVES: The study goal was to analyze the role of planned neck dissection for squamous cell carcinoma of the base of the tongue treated with definitive radiotherapy or chemoradiation. STUDY DESIGN, SETTING: We conducted a retrospective study of patients with squamous cell carcinoma of the base of the tongue undergoing planned neck dissection after definitive radiotherapy or chemoradiation. RESULTS: Twenty-two of 41 (53.7%) patients had one to six positive residual lymph nodes after receiving definitive radiotherapy or chemoradiation. Neck control rates were 92.3% and 88.3% at two and five years, respectively. Three of 22 (13.6%) patients with pathological residual nodal disease had regional or locoregional failures, compared with 1 of 19 (5.3%) patients with a pathologically complete response (P = 0.39). CONCLUSIONS: We observed a high incidence of pathologically residual lymph nodes after definitive radiotherapy or chemoradiation. SIGNIFICANCE: Planned neck dissection following definitive radiotherapy or chemoradiation is highly effective in achieving regional control of squamous cell carcinoma of the base of the tongue.

American Brachytherapy Society recommends no change for prostate permanent implant dose prescriptions using iodine-125 or palladium-103.

PURPOSE: In 2004, the American Association of Physicists in Medicine (AAPM) issued a report outlining recommended 125I and 103Pd datasets for consistency in calculating brachytherapy dose distributions. In 2005, to aid evaluating the clinical impact of implementing these datasets, the AAPM assessed the historical dependence of how prescribed doses differed from administered doses for 125I and 103Pd for permanent implantation of the prostate. Consequently, the American Brachytherapy Society (ABS) considered the nature of these changes towards issuing recommended dose prescriptions for 125I and 103Pd interstitial brachytherapy implants for monotherapy and standard boosts. METHODS AND MATERIALS: An investigation was performed of the 2005 AAPM analysis to determine changes in administered dose while affixing prescribed dose using 2004 AAPM 125I and 103Pd brachytherapy dosimetry datasets for prostate implants. For 125I and 103Pd, administered dose would change by +1.4% and +4.2%, respectively. The biological and societal impact of changing prescribed dose was considered. RESULTS: Based on the need for clinical constancy and in recognition of overall uncertainties, the ABS recommends immediate implementation of the 2004 AAPM consensus brachytherapy dosimetry datasets and no changes to 125I and 103Pd dose prescriptions at this time. CONCLUSIONS: Radiation oncologists should continue to prescribe monotherapy doses of 145 Gy and 125 Gy for 125I and 103Pd, respectively, and standard boost doses of 100-110 Gy and 90-100 Gy for 125I and 103Pd, respectively.

Treatment of oropharyngeal squamous cell carcinoma with external beam radiation combined with interstitial brachytherapy.

BACKGROUND: We reviewed the outcomes of oropharyngeal squamous cell carcinoma treated with external beam radiation and interstitial brachytherapy. METHODS: Ninety patients with squamous cell carcinoma of the oropharynx were treated with interstitial brachytherapy at the University of Utah between 1984 and 2001. Seventy-two patients received external beam radiotherapy (EBRT) followed by brachytherapy boost, 11 had surgery followed by EBRT and brachytherapy, 4 had surgery and brachytherapy, and 3 were treated with brachytherapy alone. Median doses for EBRT and brachytherapy were 50 and 24 Gy, respectively. RESULTS: Median follow-up after brachytherapy was 48.3 months for all patients. Five-year local control, disease-free survival, and overall survival were 76%, 61%, and 55%. For T1, T2, T3, and T4, 5-year local control rates were 83%, 79%, 79%, and 64%, respectively. Severe complications occurred in 13 patients, including 2 treatment-related deaths. CONCLUSIONS: EBRT combined with interstitial brachytherapy provide good local control rates for locally advanced oropharyngeal squamous cell carcinoma.

Protective effects of isoflurane pretreatment in endotoxin-induced lung injury.

BACKGROUND: The concept of antiinflammatory effects of volatile anesthetics is well established in vitro and in some organ systems. Their protective role in lung injury, however, remains to be elucidated. The authors hypothesized that in the lung, isoflurane pretreatment may attenuate neutrophil infiltration and reduce endotoxin-induced injury. METHODS: Male C57Bl/6 mice were exposed to aerosolized lipopolysaccharide. Neutrophil recruitment into the pulmonary vasculature and migration into the different lung compartments (interstitium and alveolar air space) were determined by flow cytometry. Capillary protein leakage, formation of lung edema, and concentration of the chemokines keratinocyte-derived chemokine (CXCL1) and macrophage inflammatory protein 2 (CXCL2/3) in bronchoalveolar lavage were compared in mice with or without isoflurane treatment (1.4% inspired for 30 min) at different times before and after endotoxin exposure. RESULTS: Endotoxin inhalation induced significant neutrophil migration into all lung compartments. Isoflurane pretreatment attenuated both neutrophil recruitment into lung interstitium and alveolar space when given 1 or 12 h before or 1 h after lipopolysaccharide but not at 4, 6, or 24 h before endotoxin exposure. Isoflurane pretreatment 1 or 12 h before lipopolysaccharide also reduced protein leakage and pulmonary edema. Production of CXCL1 and CXCL2/3 in the bronchoalveolar lavage was reduced when isoflurane was given 1 h but not 12 h before lipopolysaccharide, suggesting different mechanisms for early and late protection. CONCLUSION: Isoflurane pretreatment reduces acute lung injury when given 1 or 12 h before an endotoxin challenge or within the first hour of an already established inflammation.

The protective effect of protein kinase C and adenosine triphosphate-sensitive potassium channel agonists against inflammation in rat endothelium and vascular smooth muscle in vitro and in vivo.

Volatile anesthetic pretreatment protects the vasculature from inflammation-induced injury via mechanisms involving the activation of adenosine triphosphate-sensitive potassium (K(ATP)) channels and/or protein kinase C (PKC). Therefore, we hypothesized that K(ATP) and PKC agonists may mimic the protective effects of volatile anesthetics in vitro and in vivo. In vitro, rat vascular smooth muscle cells (VSM) and aortic endothelial cells (AEC) were used to evaluate whether pretreatment with a K(ATP) agonist, cromakalim (CRK), or a PKC agonist, phorbol 12-myristate 13-acetate (PMA), decreases lipopolysaccharide (LPS)-induced cell injury. Cell survival was determined by trypan blue staining after 6 h. In vivo, rats received systemic LPS or saline with or without pretreatment with PMA or CRK. Mean arterial blood pressure, the response to endothelium-dependent (acetylcholine; ACH) and -independent (sodium nitroprusside) vasodilators, and arterial blood gases were determined after 6 h. Cell survival in VSM and AEC control cultures was more than 90%, which was not altered in the presence of PMA or CRK, whereas LPS significantly decreased cell survival. PMA (0.1-10 microM) significantly attenuated the LPS-induced decrease in cell survival by 28%-37% in VSM and 39%-53% in AEC, and CRK (1 mM) increased cell survival by 24% in VSM and 22% in AEC. In vivo, PMA and CRK pretreatment had no significant effect on measured variables in control rats. LPS decreased mean arterial blood pressure and vasodilation to ACH and sodium nitroprusside and caused hypoglycemia. PMA, but not CRK, increased ACH-dependent vasodilation (46%) at 6 h, but neither agonist altered the other detrimental effects of LPS. In conclusion, PKC and K(ATP) agonists appear to protect AEC and VSM cells against inflammation in vitro, but the systemic administration of PKC and K(ATP) agonists appeared to exert minimal or no protection in our in vivo model.

Isoflurane pretreatment supports hemodynamics and leukocyte rolling velocities in rat mesentery during lipopolysaccharide-induced inflammation.

UNLABELLED: We hypothesized that the protective effects of isoflurane (ISO) pretreatment on the vasculature may be attributed, in part, to altered leukocyte-endothelial interactions. Rats were anesthetized with pentobarbital and then randomized into four groups: control, ISO-control (pretreatment with 30 min of 1.4% ISO), lipopolysaccharide (LPS; 10 mg/kg IV), and ISO-LPS (ISO pretreatment and then LPS). The mesentery was prepared for intravital videomicroscopy. Mean arterial blood pressure (MAP), along with microcirculatory variables that included postcapillary venular and arteriolar blood flow velocity and leukocyte dynamics (number of rolling and adherent leukocytes and individual rolling leukocyte velocities), were measured hourly (baseline and at 0-4 h). In LPS rats, ISO pretreatment significantly (P < 0.05) attenuated the decrease in MAP at 2 and 4 h after LPS and increased leukocyte rolling velocities after 2-4 h. Four hours after LPS, leukocyte rolling velocities were >200% more rapid (63.7 +/- 27.6 microm/s versus 19.8 +/- 6.4 micro m/s) in ISO-LPS versus LPS rats. In control rats, ISO pretreatment had no effect on MAP or leukocyte rolling velocities but increased the number of rolling leukocytes. ISO pretreatment had no effect on arteriolar and postcapillary venular blood flow velocity in LPS rats or leukocyte adherence in LPS or control rats. In conclusion, ISO pretreatment supported hemodynamics and increased leukocyte rolling velocities but did not alter the number of rolling or adherent leukocytes in the mesenteric microcirculation during LPS-induced inflammation. IMPLICATIONS: Isoflurane pretreatment supported hemodynamics and increased leukocyte rolling velocities in the mesenteric microcirculation during lipopolysaccharide-induced inflammation. Faster rolling velocities may reduce the incidence of inflammation by decreasing leukocyte-endothelial interactions and cellular injury.

Isoflurane pretreatment inhibits lipopolysaccharide-induced inflammation in rats.

BACKGROUND: Previous studies have indicated that volatile anesthetic pretreatment protects cells from inflammation; therefore, the authors hypothesized that pretreatment with isoflurane may attenuate the hemodynamic and pathologic changes to the vasculature that are associated with inflammation. METHODS: Rats received intravenous lipopolysaccharide or saline placebo with and without pretreatment with isoflurane (1.4% for 30 min immediately before lipopolysaccharide). Mean arterial pressure (MAP) and response to endothelium-dependent (acetylcholine) and -independent (sodium nitroprusside) vasodilators were assessed hourly for 6 h. Tumor necrosis factor-alpha concentrations, arterial blood gases, and vascular histology were also determined. RESULTS: Lipopolysaccharide decreased MAP and vasodilation to acetylcholine and sodium nitroprusside. Lipopolysaccharide also caused acidosis, endothelial swelling, and endothelial detachment from the smooth muscle. Isoflurane pretreatment prevented the decrease in MAP for 5 h and attenuated the decrease at 6 h. Pretreatment increased the vasodilation to acetylcholine in lipopolysaccharide rats to control concentrations but had no effect on sodium nitroprusside. In control rats, isoflurane pretreatment increased the response to acetylcholine and sodium nitroprusside but had no effect on MAP. Isoflurane pretreatment prevented the acidosis and endothelial damage to mesenteric and aortic vessels, and attenuated the increase in tumor necrosis factor-alpha associated with lipopolysaccharide-induced inflammation. CONCLUSION: Pretreatment with 30 min of isoflurane attenuated the decrease in MAP and endothelium-dependent vasodilation, the acidosis, the increase in tumor necrosis factor-alpha, and the damage to the vascular endothelium associated with lipopolysaccharide-induced inflammation in rats. This study suggests that isoflurane pretreatment may protect the vasculature during inflammation.