Influence of robotic-assisted laparoscopic hysterectomy on vaginal cuff healing and brachytherapy initiation in endometrial carcinoma patients

Publication date: July–August 2016
Source:Practical Radiation Oncology, Volume 6, Issue 4
Author(s): John M. Stahl, Henry S. Park, Dan-Arin Silasi, Masoud Azodi, Shari Damast
PurposeThe purpose of this study was to examine the impact of robotic-assisted laparoscopic hysterectomy (RALH) compared with total abdominal hysterectomy by laparotomy (TAH) on vaginal cuff healing in early-stage endometrial carcinoma patients receiving adjuvant intravaginal brachytherapy (IVBT).Methods and materialsWe included 137 consecutive patients who underwent adjuvant IVBT without external beam radiation therapy or chemotherapy for stage I-II endometrial carcinoma. All patients underwent either RALH or TAH. Vaginal cuff healing status as assessed by inspection and palpation at initial evaluation by radiation oncology (VC1) was the primary outcome, with secondary outcomes including vaginal cuff healing status at first scheduled IVBT (VC2), time interval from hysterectomy to initiation of IVBT, and local recurrence.ResultsAmong 137 patients, 74 (54.0%) underwent RALH and 63 (46.0%) underwent TAH. There was no significant difference in mean time from hysterectomy to initial radiation oncology evaluation between RALH and TAH patients (approximately 30 days in both groups). RALH was the only covariate associated with protracted vaginal cuff healing time at both VC1 (P = .003) and VC2 (P = .038). There was a significantly increased mean interval between hysterectomy and start of IVBT for patients undergoing RALH from 47.7 to 55.0 days (P < .001). Vaginal cuff healing was more likely to contribute to delay in delivery of IVBT in RALH patients, whereas abdominal or other nonvaginal wound healing was more likely to contribute to delay in TAH patients. There were no vaginal cuff recurrences detected after 16 months median follow-up.ConclusionsRALH for early-stage endometrial carcinoma was associated with longer vaginal cuff healing time and a mean increase in interval from hysterectomy to IVBT of 1 week compared with TAH.



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Factors Associated with Increased Academic Productivity Among US Academic Radiation Oncology Faculty

Publication date: Available online 1 July 2016
Source:Practical Radiation Oncology
Author(s): Catherine Zhang, Stephen Murata, Mark Murata, Clifton David Fuller, Charles R. Thomas, Mehee Choi, Emma B. Holliday
ObjectivesPublication productivity metrics can help evaluate academic faculty for hiring, promotion, grants and awards. However, limited benchmarking data exist, which makes intra- and interdepartmental comparisons difficult. Therefore, we sought to evaluate the scholarly activity of physician faculty at academic radiation oncology (RO) departments and establish factors associated with increased academic productivity.MethodsCitation database searches were performed for all physician-faculty in United States residency-affiliated academic RO departments. Demographics, NIH-funding, and bibliometrics (number of publications, Hirsch-(h)-index, and m-index) were collected and stratified by academic rank. Senior academic rank was defined as full professor, professor and/or chair. Junior academic rank was defined as all others. Logistic regression was performed to determine the association of academic rank and other factors with h- and m-indices.Results1191 academic ROs from 75 institutions were included in the analysis. The mean [standard deviation (SD)] number of publications, h- and m-indices were 48.2 [71.2], 14.5Rad et al. (2010 Jul) and 0.86 [0.83], respectively. The median [interquartile range (IQR)] number of publications, h- and m-indices were 20 [6–61], 9Ence et al. (2016 May 18), Rosenkrantz and Jiang (2016 Jun), Venable et al. (2014 Mar-Apr), Hirsch (2005 Nov 15), Anne Wil-Harzing. Reflections on the H-index (2008), Pagel and Hudetz (2015 Sep), Eloy et al. (2015 Aug), Khan et al. (2014 Mar), Klimo et al. (2014 Dec), Kulasegarah and Fenton (2010 Mar), Selek (2014), Rad et al. (2010 Jul), Association of Residents in Radiation Oncology (2015), Beatty S. Breaking the (1996), Fuller et al. (2009 Feb), Ojerholm and Swisher-McClure (2015 Nov 15), Bartneck and Kokkelmans (2011 Apr) and 0.69 [0.38–1.10], respectively. Recursive partitioning analysis revealed a statistically significant numeric h-index threshold of 21 between junior and senior faculty (LogWorth 114; ROC 0.828). Senior faculty status, receipt of NIH-funding, and a larger department size were associated with increased h- and m-indices.ConclusionsCurrent academic ROs have relatively high objective metrics of scholastic productivity compared with prior benchmarking analyses of ROs and compared to published metrics from other academic medicine subspecialties. An h-index of 21 or greater was associated with senior faculty status. Additionally, receipt of NIH funding and greater departmental size were associated with a higher h-index. These data may be of interest to faculty preparing for promotion or award applications as well as institutional leadership evaluating their departments.



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Low Dose Cranial Boost in High Risk Adult Acute Lymphoblastic Leukemia Patients Undergoing Bone Marrow Transplant

Publication date: Available online 23 June 2016
Source:Practical Radiation Oncology
Author(s): William Su, Marcher Thompson, Rendi Sheu, Amir Steinberg, Luis Isola, Richard Stock, Richard Bakst
PurposeAcute lymphoblastic leukemia (ALL) has a predilection for CNS involvement. Patients with high risk ALL are often managed with transplant using a radiation-based conditioning regimen. Historically, a high dose prophylactic cranial boost (CB) of ≥12 Gy was given to reduce risk of CNS recurrence. However, the use of CB has fallen out of favor due to toxicity concerns. In high risk adults undergoing transplant at our institution, we have used a low dose 6 Gy CB to reduce toxicity while conditioning adults with fully developed brains. The safety, efficacy, and utility of a low dose CB in adults is poorly studied. Herein, we report their outcomes and toxicity.Methods and MaterialsWe identified all high risk ALL patients undergoing TBI as part of their conditioning regimen. Those that received 6 Gy CB or no CB were included (55 total). Their charts were reviewed and statistical analyses were completed with R (version 2.15.2).ResultsIn patients undergoing CB, 3-year CNS disease free survival and overall survival were 94.7% and 62.7%. In those not undergoing CBs, survivals were 81.8% and 51.5%. Notably, within CB cohort, patients without prior CNS involvement had no CNS failures. In contrast, in non-CB cohort, there were 2 CNS failures in patients with no history of CNS involvement. In CB cohort, the only notable acute toxicity was parotitis (2.8%). Late toxicity in the CB cohort included one instance of cataracts (2.8%) without any evidence of cognitive impairment or potential radiation induced secondary malignancy.Conclusions6 Gy CB is well tolerated in the adult ALL population as part of a radiation-based conditioning regimen. Low dose CB may be considered in adult patients with high risk ALL without prior CNS involvement to reduce the likelihood of recurrence.



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Optimizing Computed Tomography Simulation Wait Times in a Busy Radiation Medicine Program

Publication date: Available online 23 June 2016
Source:Practical Radiation Oncology
Author(s): Jerry Roussos, Payam Zahedi, Tara Spence, Lue-Ann Swanson, Fionna Li-Cheung, Fred Cops, Patrick Darcy, Veng Chhin, Elen Moyo, Padraig Warde, Sophie Foxcroft, Fei-Fei Liu
PurposeAn audit was conducted of patient schedules for computed tomography simulation (CT-Sim) scans within "the Program" at "the Institution", in order to investigate opportunities for improved efficiencies, enhancing process, reducing re-scanning rates, and decreasing wait times.Methods and MaterialsA three-phased approach was undertaken to evaluate the current practice in the CT-Sim facility with a view towards implementing improvements. The first phase involved a review and assessment of the validity of current guidelines and protocols associated with 16 different disease sites. The second phase incorporated the use of a patient record and verification program MOSAIQ, to capture the duration of each appointment. The last phase allocated additional time for patient-centered care and staff engagement.ResultsThe audit revealed that efficiency could be achieved through staff training, updating protocols, and improving process coordination. With the exception of sarcoma, pediatric and palliative patients who require unique management approaches, the duration for each CT-Sim appointment was successfully shortened for all disease sites by 22-33%, corresponding to a reduction of 10-15 minutes per appointment. Re-scanning rates for patients requiring self-administered preparations prior to CT-Sim procedures were also significantly reduced by enhancing processes to increase patient compliance. Implementation of procedural changes resulted in an overall net gain of 3060 minutes, equivalent to 102 additional 30-minute CT-Sim appointment slots available for each month.ConclusionThis retrospective evaluation, review, and optimization of CT-Sim guidelines and practices identified opportunities to shorten appointment timeslots, and reduce re-scanning rates for CT-Sim procedures, thereby significantly shortening wait times and improving access to service for our patients.



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The Henri Mondor Procedure of Morbidity and Mortality Reviews (MMR) Meetings: Prospective Registration of Clinical, Dosimetric and Individual Radiosensitivity Data of Patients with Severe Radiation Toxicity

Publication date: Available online 22 July 2016
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Yazid Belkacemi, Laurianne Colson-Durand, Adeline Granzotto, Shan Husheng, Nhu Hanh To, Soufya Majdoul, Saada Guet, Marie-Laure Hervé, Gloria Fonteneau, Christian Diana, Cindy Le Bret, Claude Dominique, Maryse Fayolle, Nicolas Foray
PurposeAfter radiotherapy (RT), about one-fourth of the patients can develop various radiation-induced toxicities. An international interest has arisen in using morbidity and mortality rates to monitor the quality of care and integrate the morbidity and mortality review (MMR) meetings into their governance processes. We report the first results of patients included in our MMR procedure that included biologic assay for individual intrinsic radiosensitivity (IIRS).Materials and methodsTwenty-three patients were prospectively included in the MMR database. Twenty-two were evaluable for IIRS. Prostate (n=10) and breast (n=8) cancers were the more frequent concerned disease. The total dose delivered was according to the disease ranged from 30 Gy to 74 Gy. MMR procedure requires strict criteria: patients with unresolved grade > 3 toxicity with availability of clinical (photography) data, IIRS results obtained from skin biopsies assays, treatment modalities and follow-up data. The RT technique and dosimetry were reviewed.ResultsOur prospective registration of toxicities showed mainly 7 rectitis, 9 skin toxicities. Five out of 7 rectitis received 66 Gy post-prostatectomy RT with a V50 (rectum volume receiving 50Gy) ranged from 45 to 75% and mean maximal dose (Dmax) of 66.5Gy. For dermatitis and cystitis, the mean Dmax were in the range of classical constraints without any overdosage or dose heterogeneity. No errors have been found in the review of treatment planning and positioning. Conversely, all the patients were considered biologically as radiosensitive with genomic instability and ATM-dependent DNA double-strand break (DSB) repair impairments.ConclusionThe MMR review of files, allowed clear answers to patients on the relationship between clinical events and their IIRS. Our procedure has allowed educating all our staff to monitor, identify and document clinical, physical and biological aspects of radiation-induced toxicities. Thus, we recommend introduction of the MMR procedure in RT departments.

Teaser

Radiation-induced toxicity can induce morbidity and impact negatively the patients' quality of life. The morbidity and mortality review (MMR) meetings in radiotherapy departments aim to ensure that there is no controversy about the quality of radiotherapy delivered and to investigate other potential causes, such as the particular radiosensitivity of a patient for a given standard treatment. Our MMR procedure coupled to in skin biopsies tests showed a correlation between patients' radiosensitivity and their toxicity.


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Human papillomavirus oncoproteins differentially modulate epithelial-mesenchymal transition in 5-FU-resistant cervical cancer cells

Abstract

Etiological role of viral proteins E6 and E7 of high-risk HPV in cervical carcinogenesis is well established. However, their contribution in chemoresistance and epithelial-mesenchymal transition (EMT) that leads to advanced metastatic lesions and chemoresistance is poorly defined. In the present study, contribution of viral oncoproteins in acquisition of EMT character during onset of chemoresistance was assessed. A chemoresistant cell line (SiHaCR) was developed from an established HPV16-positive cervical cancer cell line, SiHa, by escalating selection pressure of 5-fluorouracil (5-FU). Expression of Survivin, ABCG2, Snail, Slug, Twist, and Vimentin was examined in SiHa and SiHaCR cells by reverse transcriptase-PCR (RT-PCR) and immunoblotting assays. Mesenchymal phenotype in SiHaCR cells was confirmed by assessment of migration and invasion potentials. SiHaCR cells displayed elevated level of functional and molecular markers associated with chemoresistance (Survivin, ABCG2) and EMT (Snail, Slug, Twist, Vimentin) and reduced E-cadherin. SiHaCR also showed increased levels of HPV16 E6 and E7 transcripts. Specific silencing of HPV16 E6, but not E7 using corresponding siRNA, demonstrated a differential involvement of HPV oncogenes in manifestation of EMT. HPV16 E6 silencing resulted in reduction of Slug and Twist expression. However, the expression of Snail and Vimentin was only marginally affected. In contrast, there was an increase in the expression of E-cadherin. A reduced migration and invasion capabilities were observed only in E6-silenced SiHaCR cells, which further confirmed functional contribution of HPV16 E6 in manifestation of EMT. Taken together, our study demonstrated an active involvement of HPV16 E6 in regulation of EMT, which promotes chemoresistance in cervical cancer.

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Human papillomavirus oncoproteins differentially modulate epithelial-mesenchymal transition in 5-FU-resistant cervical cancer cells

Abstract

Etiological role of viral proteins E6 and E7 of high-risk HPV in cervical carcinogenesis is well established. However, their contribution in chemoresistance and epithelial-mesenchymal transition (EMT) that leads to advanced metastatic lesions and chemoresistance is poorly defined. In the present study, contribution of viral oncoproteins in acquisition of EMT character during onset of chemoresistance was assessed. A chemoresistant cell line (SiHaCR) was developed from an established HPV16-positive cervical cancer cell line, SiHa, by escalating selection pressure of 5-fluorouracil (5-FU). Expression of Survivin, ABCG2, Snail, Slug, Twist, and Vimentin was examined in SiHa and SiHaCR cells by reverse transcriptase-PCR (RT-PCR) and immunoblotting assays. Mesenchymal phenotype in SiHaCR cells was confirmed by assessment of migration and invasion potentials. SiHaCR cells displayed elevated level of functional and molecular markers associated with chemoresistance (Survivin, ABCG2) and EMT (Snail, Slug, Twist, Vimentin) and reduced E-cadherin. SiHaCR also showed increased levels of HPV16 E6 and E7 transcripts. Specific silencing of HPV16 E6, but not E7 using corresponding siRNA, demonstrated a differential involvement of HPV oncogenes in manifestation of EMT. HPV16 E6 silencing resulted in reduction of Slug and Twist expression. However, the expression of Snail and Vimentin was only marginally affected. In contrast, there was an increase in the expression of E-cadherin. A reduced migration and invasion capabilities were observed only in E6-silenced SiHaCR cells, which further confirmed functional contribution of HPV16 E6 in manifestation of EMT. Taken together, our study demonstrated an active involvement of HPV16 E6 in regulation of EMT, which promotes chemoresistance in cervical cancer.

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