Integration of Genotype, Physiological Performance, and Survival in a Lizard (Uta stansburiana) with Alternative Mating Strategies.

Covariation among behavioral and physiological traits is thought to enhance reproductive success and Darwinian fitness. Species that exhibit alternative mating strategies provide excellent opportunities to assess the relative contributions of physiological and behavioral traits to fitness. Male side-blotched lizards (Uta stansburiana) exhibit three heritable throat color morphs that are associated with alternative mating behaviors. The three morphs differ in resource holding potential, mate attraction, mate defense, and physiological performance. We examined interrelationships of body mass, stamina, field metabolic rate, growth rate, and survival to the second capture (a fitness proxy). Relationships among variables were complex, and mass, stamina, and throat color interacted to predict male survival. Our analyses suggest that male side-blotched lizards exhibit trade-offs among physiological traits related to reproductive success and survival and that differential survival for different combinations of traits has caused correlational selection, leading to adaptive integration of phenotypic traits associated with alternative mating strategies.

Impact of prone versus supine positioning on small bowel dose with pelvic intensity modulated radiation therapy.

PURPOSE: To report the results of a prospective study that compares small bowel doses during prone and supine pelvic intensity modulated radiation therapy. METHODS AND MATERIALS: Ten patients receiving pelvic radiation therapy each had 2 intensity modulated radiation therapy plans generated: supine and prone on a belly board (PBB). Computed tomography on rails was performed weekly throughout treatment in both positions (10 scans per patient). After image fusion, doses to small bowel (SB) loops and clinical target volume were calculated for each scan. Changes between the planned and received doses were analyzed and compared between positions. The impact of bladder filling on SB dose was also assessed. RESULTS: Prone treatment was associated with significantly lower volumes of SB receiving ≥20 Gy. On average, prone on a belly board positioning reduced the volume of SB receiving a given dose of radiation by 28% compared with supine positioning. Target coverage throughout the treatment course was similar in both positions with an average minimum clinical target volume dose of 88% of the prescribed prone dose and 89% of the supine (P = .54). For supine treatment, SB dose was inversely correlated with bladder filling (P = .001-.013; P > .15 for prone). For 96% of treatments, the volume of SB that received a given dose deviated >10% from the plan. The deviation between the planned and delivered doses to SB did not differ significantly between the positions. CONCLUSIONS: Prone positioning on a belly board during pelvic IMRT consistently reduces the volume of SB that receives a broad range of radiation doses. Prone IMRT is associated with interfraction dose variation to SB that is similar to that of supine positioning. These findings suggest that prone positioning with daily image guided radiation therapy is an effective method for maximizing SB sparing during pelvic IMRT.

Ocean outfall plume characterization using an Autonomous Underwater Vehicle.

A monitoring mission to map and characterize the Point Loma Ocean Outfall (PLOO) wastewater plume using an Autonomous Underwater Vehicle (AUV) was performed on 3 March 2011. The mobility of an AUV provides a significant advantage in surveying discharge plumes over traditional cast-based methods, and when combined with optical and oceanographic sensors, provides a capability for both detecting plumes and assessing their mixing in the near and far-fields. Unique to this study is the measurement of Colored Dissolved Organic Matter (CDOM) in the discharge plume and its application for quantitative estimates of the plume's dilution. AUV mission planning methodologies for discharge plume sampling, plume characterization using onboard optical sensors, and comparison of observational data to model results are presented. The results suggest that even under variable oceanic conditions, properly planned missions for AUVs equipped with an optical CDOM sensor in addition to traditional oceanographic sensors, can accurately characterize and track ocean outfall plumes at higher resolutions than cast-based techniques.

Prospective phase I study of capecitabine and oxaliplatin concurrent with radiation therapy for the treatment of locally advanced pancreatic adenocarcinoma, and retrospective comparison to concurrent 5-fluorouracil/radiation and gemcitabine/radiation.

PURPOSE: The aims of this study is to determine the maximum tolerated dose of capecitabine and oxaliplatin (CAPOX) delivered concurrent with radiation therapy (RT) in the treatment of locally advanced pancreatic adenocarcinoma and to retrospectively compare outcomes with this regimen to concurrent 5-fluorouracil or capecitabine with RT (5FU-RT) or concurrent gemcitabine-based chemotherapy with RT (GEM-RT). MATERIALS AND METHODS: Twelve patients were enrolled in a phase I study using 50.4 Gy RT concurrent with capecitabine chemotherapy (twice daily, 7 days per week) and oxaliplatin (once weekly during weeks 1, 2, 4, and 5). Capecitabine and oxaliplatin doses were 400 mg/m(2) and 50 mg/m(2), respectively, at dose level 1; 600 mg/m(2) and 50 mg/m(2) at level 2; and 600 mg/m(2) and 60 mg/m(2) at level 3. A standard dose of gemcitabine was recommended following RT or following surgery (if done). The outcomes of patients treated with this regimen were retrospectively compared to 20 patients treated with 5FU-RT and 30 patients treated with GEM-RT. RESULTS: Dose level 3 was tolerated with acceptable toxicity. Survival in patients receiving CAPOX-RT did not differ from GEM-RT or 5FU-RT. Response of the primary tumor was observed in 38% of patients treated with CAPOX-RT, 31% of patients treated with 5FU-RT, and 66% of patients treated with GEM-RT (p = 0.03 GEM-RT versus 5FU-RT). CONCLUSIONS: CAPOX-RT has acceptable toxicity. A retrospective comparison shows higher response rate with GEM-RT versus 5FU-RT, but this difference did not translate into improvement in overall survival.

Preoperative radiation therapy for upper rectal cancer T3,T4/Nx: selectivity essential.

This review explores the current available literature regarding the role of neoadjuvant therapy for upper locally advanced rectal cancers (≥10 cm-15 cm). Although there is a paucity of data evaluating the outcomes of preoperative chemoradiation for upper rectal cancers the authors suggest that T3N0 tumors will not likely benefit from radiation and that treatment of T4N0 should be individualized.

The role of radiation therapy in the control of locoregional and metastatic cancer.

High energy X-rays have been used for cancer therapy since their discovery in 1895. Major radiobiological discoveries and technological advances in radiation physics have greatly increased the accuracy of radiation. The recent integration of radiation therapy and imaging systems provides radiation oncologists with sophisticated dose delivery capability allowing continued improvements in the control of loco-regional and metastatic disease while decreasing toxicity. Key technical aspects of current radiation therapy are described with examples extending to several clinical areas.

Secretion by the nasal salt glands of two insectivorous lizard species is initiated by an ecologically relevant dietary ion, chloride.

Salt glands are used by some vertebrates to excrete hyperosmotic NaCl or KCl solutions in response to dietary salt loads. Control of secretion varies across taxa; some secrete in response to osmotic challenges while others secrete in response to specific dietary ions. We hypothesized that differences in control could be related to different diet-related selective pressures on herbivorous, marine, and insectivorous species. We studied control of secretion and flexibility of cation (sodium or potassium) and anion (chloride or bicarbonate) secretion in two insectivorous lizard species, Schneider's skinks (Eumeces schneideri, Scincidae) and green anoles (Anolis carolinensis, Polychrotidae). Lizards were injected daily for four days with combinations of cations (potassium, sodium, and histidine control) and anions (chloride and acetate control), isoosmotic saline, or sham injection. Secretions were collected daily and analyzed for sodium, potassium, and chloride. Both species secreted only in response to chloride; sodium appeared to have a slight inhibitory effect. Regardless of cation load, skinks secreted a combination of potassium and sodium, while anoles secreted solely potassium. In both species, total cation secretion was matched closely by chloride; very little bicarbonate was secreted. As predicted, secretion in insectivorous lizards was initiated by the dietary ion ecologically most important for these species, chloride, which otherwise cannot be excreted without significant water loss (unlike the cations, which may be excreted as insoluble urate salts). This gives further support to the hypothesis that ecological factors drive the evolution of control mechanisms in lizard salt glands.

Overall and progression-free survival and visual and endocrine outcomes for patients with parasellar lesions treated with intensity-modulated stereotactic radiosurgery.

Linear accelerator single-fraction radiosurgery (SRS) for skull base lesions is usually delivered with dynamic conformal arcs (DCAs), but intensity-modulated radiosurgery (IMRS) is another option when SRS dose is limited by proximity of the optic nerve and chiasm. We review the long-term outcome of patients treated with IMRS for parasellar lesions. Fourteen patients with parasellar lesions were treated with IMRS when standard DCA radiosurgery was limited by optic nerve tolerance. Prospective patient data included endocrine function, visual acuity and field testing, nonoptic nerve cranial neuropathy, and overall survival. In addition, tumor control on serial magnetic resonance imaging is reported as progression-free survival (PFS). Six patients with cavernous sinus meningiomas and eight with recurrent pituitary adenomas were treated. Three of the pituitary tumors were hormonally active (two with Cushing disease, one with acromegaly). The median patient age was 50 years (range 24-70 years). Median follow-up was 54 months. Average tumor treatment volume was 4.99 ml (average dose 16 Gy, average of 10 IMRS fields). Tumor control was achieved in 11 of 14 (79%) patients. Median PFS has not been reached in our patient population. Thirteen patients are alive (one died of an unrelated cancer). No patients developed new endocrinological, ophthalmological, or cranial nerve deficits. IMRS allows for treatment of parasellar lesions when standard DCA SRS is limited by optic nerve tolerance. Although our follow-up period was relatively short and the number of patients was small, it appears that this can be accomplished with a high tumor control rate and survival without new endocrinopathies, optic neuropathies, or other complications in patients who have failed other therapies.

Stereotactic radiosurgery eligibility and selection bias in the treatment of glioblastoma multiforme.

Several single institution studies have shown a survival advantage when a stereotactic radiosurgery (SRS) boost followed fractionated external beam radiation (FracRT) in the treatment of glioblastoma (GBM). RTOG 93-05 employed SRS before FracRT and demonstrated no survival benefit. We examined the effect of SRS eligibility before and after FracRT on patient outcome in a group of patients treated with conventional therapy without SRS. From 1998 to 2008, 106 patients with GBM treated definitively at the University of Utah were divided into groups based on eligibility for SRS: ineligible ("Never"), eligible before FracRT ("All Pre"), eligible before FracRT only ("Pre Only"), or eligible before and after FracRT ("Always"). Overall (OS) and progression-free survival (PFS) based on SRS eligibility was assessed. Eleven patients were alive at the time of analysis with a median follow-up of 42.3 months. Median OS for groups "All Pre" (n = 29), "Always" (n = 17), "Pre Only" (n = 12), and "Never" (n = 77) were 13.6, 13.6, 12.4, and 9.2 months, respectively. Of the 29 patients in group "All Pre," 12 (41.4%) were ineligible for SRS following FracRT. PFS did not significantly differ between groups. SRS for GBM can only be of benefit to selected patients with minimal focal postoperative disease. Following FracRT, over a third of initially SRS-eligible patients demonstrated more extensive disease in our experience. It is possible inclusion of such patients in a series of SRS for GBM could mask a benefit in remaining patients. No significant difference in OS or PFS based on SRS-eligibility status was found.

Curative radiation therapy for pancreatic malignancies.

Surgery is generally considered as the only curative therapy for pancreatic cancer; however, even with optimal surgery, long-term cure is achieved in very few patients, thus highlighting the need for adjuvant therapies. Radiation therapy, usually in combination with chemotherapy, plays a role in the setting of unresectable, nonmetastatic pancreatic cancer. Its role in the adjuvant setting remains controversial and as yet undefined. This article reviews the role of radiation therapy in the adjuvant and definitive settings, and describes recent improvements in the delivery of radiotherapy that allow for improved dose delivery with decreased toxicity.

Do all locally advanced rectal cancers require radiation? A review of literature in the modern era.

Potentially curable rectal cancer is primarily treated with surgical resection. Adjuvant or neoadjuvant radiotherapy is often utilized for patients deemed to be at unacceptable risk for local recurrence. The purpose of this article is to review the pertinent literature and elucidate the role of radiotherapy in patients with an intermediate risk of local recurrence. The addition of chemoradiotherapy is recommended in the majority of patients with transmural or node positive rectal cancer. However, some patients with favorable characteristics may have only a small incremental benefit from the addition of radiotherapy. The decision to treat or not to treat should take into consideration the patient and physician tolerance of risk of recurrence and risk of treatment related toxicity. The primary factors identified for determining low risk patients are circumferential radial margin (CRM), location within the rectum, and nodal status. Patients at lowest risk have widely negative CRM (>2mm), proximal lesions (>10cm from the anal verge), and no nodal disease. Patients with all three low risk factors have an absolute reduction in local recurrence that is <5% and may be eligible to forego radiotherapy. Additional factors identified which may impact local recurrence risk are elevated serum CEA level, lymphovascular space invasion, pathologic grade, and extramural space invasion.

The role of radiation therapy in pancreas cancer.

The role of radiation therapy in pancreatic cancer continues to be investigated. Its use in the adjuvant setting remains controversial. Its use is more generally accepted in borderline resectable disease, but prospective data are sparse. Randomized trials have yielded conflicting data in locally advanced disease. Radiation techniques have improved over time, such that findings in older trials are not necessarily applicable in modern practice. This article reviews the role of radiation in resectable, borderline resectable, and unresectable pancreatic cancer.

Conformity of LINAC-based stereotactic radiosurgery using dynamic conformal arcs and micro-multileaf collimator.

PURPOSE: To assess the conformity of dynamic conformal arc linear accelerator-based stereotactic radiosurgery and to describe a standardized method of isodose surface (IDS) selection. METHODS AND MATERIALS: In 174 targets, the conformity index (CI) at the prescription IDS used for treatment was calculated as CI = (PIV/PVTV)/(PVTV/TV), where TV is the target volume, PIV (prescription isodose volume) is the total volume encompassed by the prescription IDS, and PVTV is the TV encompassed by the IDS. In addition, a "standardized" prescription IDS (sIDS) was chosen according to the following criteria: 95% of the TV was encompassed by the PIV and 99% of TV was covered by 95% of the prescription dose. The CIs at the sIDS were also calculated. RESULTS: The median CI at the prescription IDS and sIDS was 1.63 and 1.47, respectively (p < 0.001). In 132 of 174 cases, the volume of normal tissue in the PIV was reduced by the prescription to the sIDS compared with the prescription IDS, in 20 cases it remained unchanged, and in 22 cases it was increased. CONCLUSION: The CIs obtained with linear accelerator-based stereotactic radiosurgery are comparable to those previously reported for gamma knife stereotactic radiosurgery. Using a uniform method to select the sIDS, adequate target coverage was usually achievable with prescription to an IDS greater than that chosen by the treating physician (prescription IDS), providing sparing of normal tissue. Thus, the sIDS might aid physicians in identifying a prescription IDS that balances coverage and conformity.

Principles and techniques of radiation therapy for esophageal and gastroesophageal junction cancers.

Radiation therapy serves an integral role in the primary and adjuvant treatment of esophagus cancer. Radiation techniques continue to improve, providing more accurate localization of the tumor while limiting dose to normal structures. This article reviews current practices and recommendations for radiation therapy technique for esophageal and gastroesophageal malignancies.

Gonadotropin hormone modulation of testosterone, immune function, performance, and behavioral trade-offs among male morphs of the lizard Uta stansburiana.

Sexual selection predicts that trade-offs maintain trait variation in alternative reproductive strategies. Experiments often focus on testosterone (T), but the gonadotropins follicle-stimulating hormone and luteinizing hormone may provide a clearer understanding of the pleiotropic relationships among traits. We assess the activational role of gonadotropins on T and corticosterone regulation in traits expressed by polymorphic male side-blotched lizards Uta stansburiana. Gonadotropins are found to enhance and suppress multiple physiological, morphological, and behavioral traits independently, as well as indirectly via T, and we demonstrate selective trade-offs between reproduction and survival. The OBY locus, a genetic marker in our model vertebrate mating system, allows characterization of the interaction between genotype and hormone treatment on male traits. Our results suggest that oo, ob, and bb males are near their physiological and behavioral capacity for reproductive success, whereas yy and by males are maintained below their physiological maximum. Both by and yy morphs show trait plasticity, and we demonstrate that gonadotropins are likely proximate effectors that govern not only trait differences between alternative mating strategies but also morph plasticity. Gonadotropins clearly represent an important mechanism maintaining variation in physiological, morphological, and behavioral traits, as well as potentially maintaining the immunosuppression costs of male sexual signals.

Radiation therapy is associated with improved survival in patients with pancreatic adenocarcinoma: results of a study from the Surveillance, Epidemiology, and End Results (SEER) registry data.

BACKGROUND: The role of adjuvant radiation therapy in pancreatic cancer is controversial. For the current study, the authors evaluated the effect of preoperative and postoperative radiation therapy on survival in patients with pancreatic adenocarcinoma. METHODS: The analysis included 3008 patients who were reported to the Surveillance, Epidemiology, and End Results registry of the National Cancer Institute from 1988 to 2002 who had adenocarcinoma of the pancreas and who underwent cancer-directed surgery. A retrospective analysis of overall survival and cancer-specific survival for these patients was performed using the Kaplan-Meier method. Comparative risks of mortality were evaluated by using multivariate-adjusted Cox regression models. RESULTS: Of 3008 patients, 1267 (42%) received radiation therapy. Overall survival improved significantly in patients who received radiation therapy, with a median survival of 17 months and a 5-year overall survival rate of 13% in patients who received radiation compared with 12 months and 9.7%, respectively, for patients who did not receive radiation therapy (P < .0001). On multivariate analysis, radiation therapy was associated with improvement in overall survival in patients who had direct extension beyond the pancreas and/or regional lymph node involvement (P < .01) but not in patients with T1-T2N0M0 disease (P > .05). Radiation therapy was associated with improvement in cause-specific survival in patients who had regional lymph node involvement (P < .02) but not in patients who had T1-2N0M0 disease or direct extension beyond the pancreas without lymph node involvement (P > .05). Differences in overall and cause-specific survival among patients who received preoperative versus postoperative radiation therapy did not reach statistical significance. CONCLUSIONS: Radiation therapy was associated with improved survival compared with cancer-directed surgery without radiation in patients with adenocarcinoma of the pancreas.