Primary ovarian carcinoid: A report of two cases and a decade registry

Publication date: Available online 9 July 2016
Source:Journal of the Egyptian National Cancer Institute
Author(s): Islam H. Metwally, Amr F. Elalfy, Shadi Awny, Islam A. Elzahaby, Reham M. Abdelghani
ObjectivesThis study aims at reporting 2 cases of primary ovarian carcinoid tumor, and providing an adequate registry of such cases and how they were managed.Methods2 female patients with primary ovarian carcinoid were diagnosed and treated in our center. Discussion of their presentation, pathology and treatment is entitled. Also a thorough search of all published registries and case reports of ovarian carcinoid was done with analysis of reported data.Results164 cases of primary ovarian carcinoid tumor were detected since 2005 with the predominance of the insular variant. Carcinoid syndrome occurs in nearly 14% of these cases. Most of the cases were treated with hysterectomy. Unfortunately, the prognosis was not documented in most series.ConclusionPrimary ovarian carcinoid is a relatively rare disease with an indolent course and excellent outcome. Carcinoid syndrome, especially carcinoid heart disease may worsen the prognosis. Total abdominal hysterectomy with bilateral salpingo-oophorectomy has been commonly used as the treatment of choice of primary ovarian carcinoid tumors.



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Carcinoma of Gall bladder with distant metastasis to breast parenchyma. Report of a case and review of literature

Publication date: Available online 2 July 2016
Source:Journal of the Egyptian National Cancer Institute
Author(s): Damodara Kumaran, Manikandan Anamalai, Umesh Velu, Aruna Nambirajan, Pramod Kumar Julka
BackgroundGall bladder carcinoma is one of the most common cancers in India. Gall bladder cancer with metastasis to the breast is very rare. Herein we intend to report a case of carcinoma gall bladder with breast metastasis and a short review of the literature.MethodsThis report describes an interesting and unusual case of gall bladder carcinoma presenting with breast metastasis.Case reportA 38-year lady presented with complaints of right abdominal pain. Bilateral breast examination showed 2×2cm palpable lump in the upper outer quadrant of the left breast. Contrast-enhanced CT of the abdomen and pelvis showed circumferential thickening of gall bladder with the loss of fat plane with the adjacent liver parenchyma. Biopsy from the breast lump was reported as metastatic adenocarcinoma compatible with primary in the gall bladder. Whole body PET-CT showed gall bladder mass with abdominal and pelvic nodes with metastasis to liver, left breast, C7 vertebral body and left supra-clavicular node. She was diagnosed to have disseminated carcinoma gall bladder with liver, breast and supraclavicular nodal metastasis. She received palliative chemotherapy with gemcitabine and carboplatin and radiotherapy to C7 vertebra. After receiving 3 cycles of chemotherapy, chemotherapy was changed to the second line with single agent capecitabine. In spite of two lines of chemotherapy, she succumbed to disease progression and expired.ConclusionThere are limited examples of gall bladder adenocarcinoma with simultaneous metastasis to breast in the English literature. Our case showed an unusual dissemination of gall bladder cancer.



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Prevalence of hepatocellular carcinoma in chronic hepatitis C patients in Mid Delta, Egypt: A single center study

Publication date: Available online 1 July 2016
Source:Journal of the Egyptian National Cancer Institute
Author(s): Dina H. Ziada, Sherif El Sadany, Hanan Soliman, Sherief Abd-Elsalam, Marwa Salama, Nehad Hawash, Amal Selim, Manal Hamisa, Hala M. Elsabagh
Background and aimHepatocellular carcinoma (HCC) has an increasing incidence worldwide. In this study we aimed to assess the prevalence of HCC among HCV patients in our center in Mid Delta, Egypt.Patients and methodsDuring the period between April 2013 and January 2015, we screened sequentially chronic HCV patients attending inpatient wards or outpatient Clinic of Tropical Medicine Department in Tanta University Hospital for HCC. Individuals with focal lesion in Ultrasound (US) and/or serum α-fetoprotein (AFP) level >200ng/ml were examined by triphasic computed tomography scanning (CT), and/or magnetic resonance imaging (MRI).ResultsAmong 514 HCV patients interviewed and accepted sharing in this study, 90 (17.5%), 144 (28%), and 280 (54.5%) were Child A, B, and C, respectively. We found that 108/514 patients (21%) had focal lesion detected by US. Also, 89/514 (17.3%) had elevated AFP >200, 13 of them (14.6%) had no focal lesion on US, but further work up showed HCC in 2 of them. Overall HCC diagnosis was confirmed in 103 cases, 94 of them (91.3%) were Child B or C. Occurrence of HCC was significantly higher in smokers, diabetics, patients with decompensated liver and those with positive family history of HCC. Only 20/103 (19.4%) were candidates to curative treatments, 8 of them were Child A asymptomatic and discovered accidentally during screening.ConclusionThe high prevalence of HCC in our HCV patients (22%) was mainly associated with decompensated cirrhosis. A national surveillance program for the detection of HCC in cirrhotic HCV Egyptian patients by combining ultrasound examination and AFP is highly recommended.



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Expression of cyclooxygenase 2 and vascular endothelial growth factor in gastric carcinoma: Relationship with clinicopathological parameters

Publication date: Available online 21 June 2016
Source:Journal of the Egyptian National Cancer Institute
Author(s): Nesreen H. Hafez, Neveen S. Tahoun
BackgroundGastric cancer is one of the most common cancers and the second most common cause of cancer-related death worldwide. Identification of specific prognostic indicators might allow a better prognostic stratification and more effective therapy.AimTo assess the expression and relationship between COX-2 and VEGF protein in gastric adenocarcinoma and whether these markers are useful in predicting clinicopathological prognostic parameters.Materials and methodsThe study included 83 formalin-fixed paraffin embedded tissue samples of excised gastric adenocarcinoma and 20 non tumorous tissue controls. The slides were subjected to COX-2 and VEGF immunohistochemical staining using a streptavidin–biotinperoxidase according to the manufacturer's protocol. The results were assessed independently by two pathologists. The relationships among COX-2 and VEGF expression and clinicopathological parameters were statistically analyzed.ResultsCOX-2 and VEGF expressions were obviously higher in carcinoma tissues compared to normal mucosae (p<0.001). The expression rate of COX-2 was 54.2% and of VEGF was 68.7%. COX-2 positive tumors were significantly correlated with Lauren classification, tumor depth and Helicobacter pylori infection (p<0.001, p=0.008, p=0.035). VEGF was significantly associated with lymph node metastasis and tumor depth (p<0.001). There was a positive association between VEGF and COX-2 expression in gastric adenocarcinoma (Kappa value=0.55).ConclusionIn gastric adenocarcinoma, COX-2 expression might serve as a powerful indicator for intestinal type carcinoma, locally advanced disease and H. pylori infection, while VEGF was related to loco-regional progression. COX-2 might be involved in the development of angiogenesis in gastric carcinoma through VEGF upregulation.



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Results of treatment of lymphoblastic lymphoma at the children cancer hospital Egypt – A single center experience

Publication date: Available online 20 June 2016
Source:Journal of the Egyptian National Cancer Institute
Author(s): Hany Abdel Rahman Sayed, Mohamed Sedky, Asmaa Hamoda, Naglaa El Kinaaie, Madeha El Wakeel, Dina Hesham
IntroductionLymphoblastic lymphoma (LBL) and acute lymphoblastic leukemia (ALL) are neoplasms of immature B or T-cell precursors. They are considered as a unique biological entity in the 2008 World Health Organization Classification of Hematologic Neoplasm. Both entities are arbitrarily separated by a cut-off point of 20–25% of blast cells in the bone marrow. Treatment of LBL has evolved over time from conventional high-grade NHL schedules to ALL-derived protocols.The aim of this work is to report the clinical characteristics, overall survival (OS), event free survival (EFS), and common chemotherapy toxicities of lymphoblastic lymphoma (LBL) patients during a 5.5year period.Patients and methodsA Retrospective review of patient's charts diagnosed and treated as LBL during the period between July 2007 and end of December 2012 was done. Patients were treated according to St. Jude Children Research Hospital ALL Total Therapy XV protocol, standard risk arm.ResultsThis study included 77 patients. T-cell LBL patients were 67, while 10 were of B-cell origin. The median age at diagnosis was 9years (95% CI: 7–10). The majority were males 54/77. Stage III patients were 51, stage IV 13, stage II 11 and stage I 2 patients. Two patients were excluded from analysis as they died before receiving chemotherapy. Complete remission post induction chemotherapy was seen in 22 patients considered early responders, and partial remission in 55 considered late responders. With a median follow up duration of 47months (95% CI: 38–56), the 4year overall survival and event free survival were 86.45% (95% CI: 73.78–94.09) and 82.18% (95% CI: 69.25–90.61) respectively.Twelve patients died during the study period; 2 early deaths before starting chemotherapy from disease progression, 2 in CR due to chemotherapy related toxicity and 8 from disease progression. All the relapsed patients were T-cell, had advanced disease at presentation (6 with stage III; 2 with stage IV). Two patients (2.6%) had isolated local, BM, and CNS relapse each, while 1 (1.3%) had both local and CNS relapse. Disease recurrence was local in 3 patients (3.9%), and systemic in 5 (6.4%), while it was early in 6 (7.8%), and late in 2 (2.6%) patients. Median time to disease progression was 20months (range 5–39months). All relapsed patients did not survive salvage chemotherapy. The most common chemotherapy toxicities were cerebral venous thrombosis (20%), followed by bone infarcts (10.6%), and avascular necrosis (AVN) of head of femur (9.3%). One patient developed secondary acute myeloid leukemia after 3years of FU with unfavorable cytogenetic abnormalities.ConclusionResults of treatment of LBL on the St Jude's total therapy XV study are comparable to most of the similar reported studies. Outcome of relapsing patients is extremely poor, hence there is a need to identify biologic or clinical prognostic factors including minimal residual tumor to better evaluate chemotherapy response. Steroid induced AVN, and cerebral vascular thrombosis were the main chemotherapeutic adverse events.



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Phyllodes tumors of the breast: Analysis of 35 cases from a single institution

Publication date: Available online 9 July 2016
Source:Journal of the Egyptian National Cancer Institute
Author(s): Gerges Attia Demian, Salah Fayaz, Heba El-Sayed Eissa, Nashwa Nazmy, Suzanne Samir, Thomas George, Mustafa El-Sherify, Sadeq Abuzalouf
BackgroundPhyllodes tumors are rare fibroepithelial breast tumors with diverse biological behavior. Our study aim is to review the clinico-pathological features, prognostic factors and treatment outcome for patients presenting with phyllodes tumors of the breast to the Kuwait Cancer Control Center (KCCC).Patients and methodsWe retrospectively reviewed the clinical and pathological data of 35 women of histologically proved phyllodes tumors of the breast retrieved between January 1994 and December 2012.ResultsThe median age was 40years (21–63years). The median pathological tumor size was 6.8cm (3–25cm). Histologically, one patient (3%) presented with benign, 13 (37%) with borderline and 21 (60%) with malignant phyllodes. Twenty-eight patients (80%) were premenopausal. Twenty (57%) were ultimately treated with mastectomy (3 borderline, and 17 malignant) and 15 (43%) with conservative surgery (1 benign, 10 borderline and 4 malignant). Axillary staging was carried out in 9 patients (1 borderline and 8 malignant), none of them had nodal metastasis. Four patients with malignant phyllodes received postoperative radiotherapy. After a median follow-up period of 52months (range 5–211months), 5 developed local recurrence (1 benign, 2 borderline and 2 malignant). One patient with malignant phyllodes developed distant lung metastasis. The overall 5-year relapse free survival (RFS) was 74% (68% for borderline and 84% for malignant phyllodes). According to the treatment modality, the 5-year RFS was 69% for conservative surgery compared to 87% for mastectomy. It was 100% for irradiated patients versus 71% for non irradiated patients.ConclusionPhyllodes tumors are rare tumors that occur in relatively young women, when compared with the classical adenocarcinoma of the breast. They have a tendency to reach large sizes with absence of nodal metastasis. Although surgery is the mainstay of management, postoperative radiotherapy also appears to decrease the local recurrence rates in certain presentations.



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Mitochondria and oxidative stress in heart aging

Abstract

As average lifespan of humans increases in western countries, cardiac diseases become the first cause of death. Aging is among the most important risk factors that increase susceptibility for developing cardiovascular diseases. The heart has very aerobic metabolism, and is highly dependent on mitochondrial function, since mitochondria generate more than 90 % of the intracellular ATP consumed by cardiomyocytes. In the last few decades, several investigations have supported the relevance of mitochondria and oxidative stress both in heart aging and in the development of cardiac diseases such as heart failure, cardiac hypertrophy, and diabetic cardiomyopathy. In the current review, we compile different studies corroborating this role. Increased mitochondria DNA instability, impaired bioenergetic efficiency, enhanced apoptosis, and inflammation processes are some of the events related to mitochondria that occur in aging heart, leading to reduced cellular survival and cardiac dysfunction. Knowing the mitochondrial mechanisms involved in the aging process will provide a better understanding of them and allow finding approaches to more efficiently improve this process.

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Assessment of dose variation for accelerated partial breast irradiation using rigid and deformable image registrations

Publication date: Available online 23 June 2016
Source:Practical Radiation Oncology
Author(s): Vikneswary Batumalai, Lois Holloway, Amy Walker, Michael Jameson, Geoff P. Delaney
PurposeThe aim of this study was to estimate the delivered dose to the target and organs at risk (OAR) for external beam accelerated partial breast irradiation (APBI) accounting for day-to-day setup uncertainties, using rigid and deformable image registration.Methods and MaterialsOne planning computed tomography (CT) scan and five cone-beam CT (CBCT) scans for each of 25 patients previously treated with tangential breast radiotherapy were used. All CBCT scans were registered to the planning-CT scan using three techniques; i) rigid registration based on bony-anatomy only, ii) rigid registration based on soft-tissue only, and iii) deformable image registration. For each patient, four dose distributions were calculated for APBI. The first dose distribution was the original plan. The other three were "dose-of-the-day" for each of the registration approaches. The effects of image registrations on estimating delivered dose to targets and organs at risk (OAR) were determined.ResultsThe average reductions in V95 (percentage of the PTV that received 95% of the prescribed dose) were 6%, 7%, and 5% for bone, soft-tissue and deformable registrations, respectively. The average increase in mean dose to the heart were 9%, 9% and 18% for bone, soft-tissue and deformable registrations, respectively, while the average increase in maximum dose to the contralateral breast were 19%, 20%, and 28%, respectively.ConclusionsThe results of this study have shown that there are differences between the planned and estimated delivered dose for APBI due to day-to-day setup uncertainties which may need to be accounted for. Estimated dosimetric impact of setup variation and breast deformation assessed using deformable registration was greater for OARs and smaller for target volumes compared to rigid registration.



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The World's First Single-Room Proton Therapy Facility - Two-Year Experience

Publication date: Available online 9 July 2016
Source:Practical Radiation Oncology
Author(s): Jessika Contreras, Tianyu Zhao, Stephanie Perkins, Baozhou Sun, Sreekrishna Goddu, Sasa Mutic, Beth Bottani, Sharon Endicott, Jeff Michalski, Clifford Robinson, Christina Tsien, Jiayi Huang, Benjamin W. Fischer-Valuck, Dennis Hallahan, Eric Klein, Jeffrey Bradley
PurposeA review of our 2-year experience with the first single-gantry proton therapy (PT) system.Methods and Materials.All patients were consented to participate on an IRB-approved prospective patient registry between 12/2013 and 12/2015. PT was delivered in a single room facility using a synchrocyclotron with proton beam energy of 250MeV. The dataset was interrogated for demographics, diagnosis, treatment modality, and clinical trial involvement. Cases were classified as simple or complex based on fields used and immobilization. The volume of photon patients treated in our department was collected between 1/2011 and 12/2015 to evaluate the impact of PT on our photon patient volume.ResultsA total of 278 patients were treated with PT, including 228 (82%) adults and 50 (18%) pediatric cases. PT patients traveled a mean distance of 83.3miles compared to 47.4miles for photon patients queried in 2015. Rationale for treatment included re-irradiation (20%), involvement in prospective clinical trial (14%), and proximity to critical structures to maximally spare organs at risk (66%). Forty patients were enrolled on 5 adult and 3 pediatric prospective clinical trials. The most common histologies treated were glioma (27%) and non-small cell lung cancer (18%) in adults, and medulloblastoma (22%) and low-grade glioma (24%) in pediatric patients. Prostate cancer comprised 6% of PT. Complex cases comprised 45% of our volume. Our photon patient volume increased yearly between 2011–2015, with 2780 patients completing photon treatment in 2011 and 3385 patients in 2015. PT comprised 4% of overall patients treated with external beam radiation.ConclusionsThe installation of our single gantry proton facility has expanded the treatment options within our cancer center, helping to increase the number of patients we see. Patients travel from twice as far away to receive this treatment, many for typical proton therapy indications such as pediatrics or to participate in prospective clinical trials.



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Estimating the Excess Lifetime Risk of Radiation Induced Secondary Malignancy (SMN) in Pediatric Patients Treated with Craniospinal Irradiation (CSI): Conventional Radiotherapy vs. Helical Intensity Modulated Radiotherapy

Publication date: Available online 8 July 2016
Source:Practical Radiation Oncology
Author(s): Jordan A. Holmes, Bhishamjit S. Chera, David J. Brenner, Igor Shuryak, Adam K. Wilson, Misty Lehman-Davis, David V. Fried, Vivek Somasundaram, Jun Lian, Tim Cullip, Lawrence B. Marks




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Comparison of Two Transabdominal Ultrasound Image Guidance Systems for Prostate and Prostatic Fossa Radiotherapy

Publication date: Available online 8 July 2016
Source:Practical Radiation Oncology
Author(s): Bill J. Salter, Martin Szegedi, Christine Boehm, Vikren Sarkar, Prema Rassiah-Szegedi, Brian Wang, Hui Zhao, Jessica Huang, Long Huang, Kris Kokeny, Jonathan D. Tward
PurposeOur clinic is a long-term user of a 1^stgeneration transabdominal (TA) Bi-Planar (2.5D) Ultrasound Image Guidance (USIG) system for prostate cancer treatments. We are also an early adopter and development partner for a new, second generation, fully 3D USIG system which allows for volumetric TA localization of the prostate. This new system has been evaluated at our institution by direct comparison with the previously established 1st generation TA method for prostate alignment.Methods and MaterialsWe compared the two TA-USIG methods on the same subjects, same treatment sessions. 1428 fractions delivered to 41 treated patients (16 intact prostate, 25 fossa) were analyzed regarding the agreement of alignments between the two US positioning systems. Patients were first aligned to tattoos using treatment room lasers. TA-USIG using the 3D system was then performed to align contours derived during the CT simulation process to their corresponding daily ultrasound-visualized structures. The US-3D system image guidance shifts were performed and recorded as the "initial" shifts. A 2.5D system alignment was then immediately performed using the same CT derived reference contours and the indicated shifts, relative to the 3D system, were recorded as the difference between the two alignment methods.ResultsThe average difference between the two TA-USIG alignments for all patients was 0.4±0.7mm, 0.7±0.9mm, and 0.5±0.9mm in the left–right, anterior–posterior, and superior–inferior directions, respectively. No significant difference in system agreement between intact prostate versus fossa patients was observed.ConclusionOur comparison of an established 2.5D USIG method with a newer, fully 3D approach for prostate alignment of 41 different patients (1428 fractions) shows excellent agreement with each other, despite the non-trivial difference in imaging approaches. This shows that the two specific USIG approaches yield results that are consistent with each other, and that the USIG modality yields consistent results within the modality.



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Radiation Induced Tonsillar Atrophy

Publication date: Available online 4 July 2016
Source:Practical Radiation Oncology
Author(s): Arthur K. Liu




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Masthead

Publication date: July–August 2016
Source:Practical Radiation Oncology, Volume 6, Issue 4





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Receiver Operating Curves and Dose-Volume Analysis of Late Toxicity with Stereotactic Body Radiotherapy for Prostate Cancer

Publication date: Available online 17 July 2016
Source:Practical Radiation Oncology
Author(s): Li Zhang, Julian Johnson, Alexander R. Gottschalk, Albert J. Chang, I-Chow Hsu, Mack Roach, Zachary A. Seymour
PurposeThe purpose of this study was to evaluate a receiver operating characteristic (ROC) curve method to determine dose thresholds with late genitourinary (GU) toxicity after stereotactic body radiation therapy (SBRT) for prostate cancer.Methods and materialsSeventy-eight patients diagnosed with low- to intermediate-risk prostate cancer and treated with SBRT alone were reviewed retrospectively. All patients received a total dose of 38Gy in 4 fractions with a planning target volume expansion of 2mm. GU toxicity was documented according to the Common Terminology Criteria for Adverse Events (version 4). ROC analysis applied on a logistic regression model was used to determine optimal dosimetric parameters for GU toxicity.ResultsThe median age at treatment was 69years with a median prostate volume of 46.2mL. The median prescription isodose line was 67% (interquartile range: 65–70%). The median clinical follow-up was 35.49months. Late grade 1, 2, and 3 GU toxicity occurred in 21.8%, 19.2%, and 2.6% of cases, respectively. Late grade 2+GU toxicity was associated with prescription isodose line (p=0.009) and normalized volumes for heterogeneity ≥46Gy. The ROC method successfully produced thresholds for dose-volume recommendations for both prostate and urethra, including a normalized prostate volumes from 46–50Gy, such as V46Gy of 36.7% (sensitivity 71%, specificity 61%, AUC 0.67) with an associated probability of late GU grade 2+ toxicity of 21%.ConclusionsIntraprostatic heterogeneity should be controlled with potential thresholds at V46Gy <36.7%, V48Gy <21%, and V50Gy <9.5% of the normalized prostate volume to keep late grade 2+ GU toxicity ≤20% with four fraction schemes. This may be facilitated with a higher prescription IDL (>69%).



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Editorial Board

Publication date: July–August 2016
Source:Practical Radiation Oncology, Volume 6, Issue 4





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Early and Multiple PSA Bounces Can Occur Following High Dose Prostate Stereotactic Body Radiation Therapy: Subset Analysis of a Phase I/II Trial

Publication date: Available online 24 June 2016
Source:Practical Radiation Oncology
Author(s): D. Nathan Kim, Christopher Straka, L. Chinsoo Cho, Yair Lotan, Jingsheng Yan, Brian Kavanagh, David Raben, Susan Cooley, Jeffrey Brindle, Xian Jin Xie, David Pistenmaa, Robert Timmerman
Purpose/ObjectivesWe hypothesized that high dose Stereotactic Body Radiation Therapy (SBRT) would lead to faster time to nadir and lower nadir values compared to conventional radiation therapy experiences. We now report PSA kinetics following high dose SBRT in patients treated with radiation alone.Materials/Methods91 patients were enrolled on the phase I/II dose escalation study of SBRT for localized prostate cancer (PCa). All patients with at least 36months (m) of follow up and without hormone therapy were included for this analysis (n=47). Treatment response parameters evaluated include time to nadir, nadir value, occurrence of PSA bounces (rise of ≥0.2ng/mL followed by a subsequent fall), magnitude of bounces, duration of bounces and correlation of bounces with clinical outcomes.ResultsMedian follow up was 42m (range 36–78m). Treatment dose levels were 45 Gray (Gy) (n=10), 47.5Gy (n=8) and 50Gy (n=29) in 5 fractions. Biochemical control rate was 98%. Median PSA at follow up was 0.10±0.20ng/mL. Median time to nadir was 36±11m. 24/47 (51.1%) patients had ≥1 PSA bounce. Median magnitude of PSA rise during bounce was 0.50±1.2ng/mL. Median time to first bounce was 9±7.0m. Median bounce duration was 3±2.3m for the first bounce and 6±5.2m for subsequent bounces. Prostate volumes <30cc were associated with a decreased likelihood of bounce (p=0.0202), and increasing prostate volume correlated with increasingly likelihood of having ≥2 bounces (p=0.027). Patients reaching PSA nadir of ≤0.1ng/mL were less likely to experience any bounce (p=0.0044).ConclusionsCompared to other SBRT experiences, our study demonstrated a higher PSA bounce rate, a similar or shorter median time to bounce and a very low nadir. Prostate volume appears correlated with bounce.



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Table of Contents

Publication date: July–August 2016
Source:Practical Radiation Oncology, Volume 6, Issue 4





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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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