Bassem Youssef

Inter-Institutional Comparison of Personalized Risk Assessments for Second Malignant Neoplasms for a 13-Year-Old Girl Receiving Proton versus Photon Craniospinal Irradiation

Children receiving radiotherapy face the probability of a subsequent malignant neoplasm (SMN). In some cases, the predicted SMN risk can be reduced by proton therapy. The purpose of this study was to apply the most comprehensive dose assessment methods to estimate the reduction in SMN risk after proton therapy vs. photon therapy for a 13-year-old girl requiring craniospinal irradiation (CSI). We reconstructed the equivalent dose throughout the patient’s body from therapeutic and stray radiation and applied SMN incidence and mortality risk models for each modality. Excluding skin cancer, the risk of incidence after proton CSI was a third of that of photon CSI. The predicted absolute SMN risks were high. For photon CSI, the SMN incidence rates greater than 10% were for thyroid, non-melanoma skin, lung, colon, stomach, and other solid cancers, and for proton CSI they were non-melanoma skin, lung, and other solid cancers. In each setting, lung cancer accounted for half the risk of mortality. In conclusion, the predicted SMN risk for a 13-year-old girl undergoing proton CSI was reduced vs. photon CSI. This study demonstrates the feasibility of inter-institutional whole-body dose and risk assessments and also serves as a model for including risk estimation in personalized cancer care.

Low- and middle-income countries can reduce risks of subsequent neoplasms by referring pediatric craniospinal cases to centralized proton treatment centers

Few children with cancer in low- and middle-income countries (LMICs) have access to proton therapy. Evidence exists to support replacing photon therapy with proton therapy to reduce the incidence of secondary malignant neoplasms (SMNs) in childhood cancer survivors. The purpose of this study was to estimate the potential reduction in SMN incidence and in SMN mortality for pediatric medulloblastoma patients in LMICs if proton therapy were made available to them. For nine children of ages 2 to 14 years, we calculated the equivalent dose in organs or tissues at risk for radiogenic SMNs from therapeutic and stray radiation for photon craniospinal irradiation (CSI) in a LMIC and proton CSI in a high-income country. We projected the lifetime risks of SMN incidence and SMN mortality for every SMN site with a widely-used model from the literature. We found that the average total lifetime attributable risks of incidence and mortality were very high for both photon CSI (168% and 41%, respectively) and proton CSI (88% and 26%, respectively). SMNs having the highest risk of mortality were lung cancer (16%), non-site-specific solid tumors (16%), colon cancer (5.9%), leukemia (5.4%), and for girls breast cancer (5.0%) after photon CSI and non-site-specific solid tumors (12%), lung cancer (11%), and leukemia (4.8%) after proton CSI. The risks were higher for younger children than for older children and higher for girls than for boys. The ratios of proton CSI to photon CSI of total risks of SMN incidence and mortality were 0.56 (95% CI, 0.37 to 0.75) and 0.64 (95% CI, 0.45 to 0.82), respectively, averaged over this sample group. In conclusion, proton therapy has the potential to lessen markedly subsequent SMNs and SMN fatalities in survivors of childhood medulloblastoma in LMICs, for example, through regional centralized care. Additional methods should be explored urgently to reduce therapeutic-field doses in organs and tissues at risk for SMN, especially in the lungs, colon, and breast tissues.

Investigation of radiomic signatures for local recurrence using primary tumor texture analysis in oropharyngeal head and neck cancer patients

Radiomics is one such “big data” approach that applies advanced image refining/data characterization algorithms to generate imaging features that can quantitatively classify tumor phenotypes in a non-invasive manner. We hypothesize that certain textural features of oropharyngeal cancer (OPC) primary tumors will have statistically significant correlations to patient outcomes such as local control. Patients from an IRB-approved database dispositioned to (chemo)radiotherapy for locally advanced OPC were included in this retrospective series. Pretreatment contrast CT scans were extracted and radiomics-based analysis of gross tumor volume of the primary disease (GTVp) were performed using imaging biomarker explorer (IBEX) software that runs in Matlab platform. Data set was randomly divided into a training dataset and test and tuning holdback dataset. Machine learning methods were applied to yield a radiomic signature consisting of features with minimal overlap and maximum prognostic significance. The radiomic signature was adapted to discriminate patients, in concordance with other key clinical prognosticators. 465 patients were available for analysis. A signature composed of 2 radiomic features from pre-therapy imaging was derived, based on the Intensity Direct and Neighbor Intensity Difference methods. Analysis of resultant groupings showed robust discrimination of recurrence probability and Kaplan-Meier-estimated local control rate (LCR) differences between “favorable” and “unfavorable” clusters were noted.

Model for Estimating Power and Downtime Effects on Teletherapy Units in Low-Resource Settings

Purpose More than 6,500 megavoltage teletherapy units are needed worldwide, many in low-resource settings. Cobalt-60 units or linear accelerators (linacs) can fill this need. We have evaluated machine performance on the basis of patient throughput to provide insight into machine viability under various conditions in such a way that conclusions can be generalized to a vast array of clinical scenarios. Materials and Methods Data from patient treatment plans, peer-reviewed studies, and international organizations were combined to assess the relative patient throughput of linacs and cobalt-60 units that deliver radiotherapy with standard techniques under various power and maintenance support conditions. Data concerning the frequency and duration of power outages and downtime characteristics of the machines were used to model teletherapy operation in low-resource settings. Results Modeled average daily throughput was decreased for linacs because of lack of power infrastructure and for cobalt-60 units because of limited and decaying source strength. For conformal radiotherapy delivered with multileaf collimators, average daily patient throughput over 8 years of operation was equal for cobalt-60 units and linacs when an average of 1.83 hours of power outage occurred per 10-hour working day. Relative to conformal treatments delivered with multileaf collimators on the respective machines, the use of advanced techniques on linacs decreased throughput between 20% and 32% and, for cobalt machines, the need to manually place blocks reduced throughput up to 37%. Conclusion Our patient throughput data indicate that cobalt-60 units are generally best suited for implementation when machine operation might be 70% or less of total operable time because of power outages or mechanical repair. However, each implementation scenario is unique and requires consideration of all variables affecting implementation.

Intraoperative Radiation Therapy: A Promising Treatment Modality in Head and Neck Cancer

Every year, almost 62,000 are diagnosed with a head and neck cancer (HNC) and 13,000 will succumb to their disease. In the primary setting, intraoperative radiation therapy (IORT) can be used as a boost in select patients in order to optimize local control. Addition of external beam radiation to limited volumes results in improved disease control over surgery and IORT alone. In the recurrent setting, IORT can improve outcomes from salvage surgery especially in patients previously treated with external beam radiation. The use of IORT remains limited to select institutions with various modalities being currently employed including orthovoltage, electrons, and high-dose rate brachytherapy. Practically, execution of IORT requires a coordinated effort and careful planning by a multidisciplinary team involving the head and neck surgeon, radiation oncologist, and physicist. The current review summarizes common uses, outcomes, toxicities, and technical aspects of IORT in HNC patients.

Anaplastic Meningioma Presenting as a Left Parietal Mass: A Case Report

Patient: Female, 67 Final Diagnosis: Meningioma Symptoms: Headache Medication: — Clinical Procedure:— Specialty: Oncology Objective: Unusual clinical course Background: Meningiomas are slow-growing tumors attached to the dura mater and are composed of neoplastic meningothelial cells. The tumors are most commonly located in convexities, and it is relatively rare to find such a growth in the parietal region such as the one presented in this case report. Case Report: Because of its uncommon presentation, we hereby report the case of a 67-year-old, previously healthy, white Lebanese female patient who presented with forgetfulness, unsteady gait, right-sided motor weakness, and dysphagia. She was found to have an anaplastic meningioma located in the left parietal lobe that was treated by surgical resection. The patient had an uneventful postoperative course, and was stable at later follow-ups. Conclusions: This case report describes the clinical presentation, pathological findings, and the prognosis of this mass, which is atypical in this location, and has been rarely reported in the literature. We also review the literature on anaplastic meningiomas.

Trastuzumab Emtansine for the Treatment of HER-2 Positive Carcinoma Ex-Pleomorphic Adenoma Metastatic to the Brain: A Case Report.

Background: Carcinoma Ex-pleomorphic adenoma is a malignant transformation of the common benign neoplasm of the salivary glands, “pleomorphic adenoma.” Only two cases were ever reported with brain metastases, with absence of good evidence guiding management of such cases. Case Presentation: A 61-year-old woman presenting with facial paralysis was found to have carcinoma ex-pleomorphic adenoma of the parotid gland. Twenty months after local treatment, she developed brain metastases, treated with whole brain radiation therapy. The patient then had progressive intracranial disease after the end of radiation therapy in addition to the appearance of liver metastases. Pathology showed overexpression of HER2, so she was treated with Trastuzumab Emtansine (TDM1). Follow-up imaging revealed significant decrease in the number and size of the metastatic brain lesions in keeping with a good response to TDM1 treatment. Conclusion: Prognosis of metastatic carcinoma ex-pleomorphic adenoma is very poor, and there is no clear management for such cases. We present a case of carcinoma ex-pleomorphic adenoma with brain and liver metastases with a very good response to TDM1 treatment.

Randomized, Prospective, Open-label Phase III Trial Comparing Mebo Ointment With Biafine Cream for the Management of Acute Dermatitis During Radiotherapy for Breast Cancer

Purpose: Acute radiation dermatitis is a common side-effect of radiotherapy in breast cancer and has a profound impact on patients’ quality of life, due to pain and discomfort. The aim of this study is to compare the effect of &bgr;-sitosterol (Mebo) ointment to trolamine (Biafine) cream for the prevention and treatment of radiation dermatitis in breast cancer patients receiving adjuvant radiation therapy. Materials and Methods: This is a prospective open-label randomized phase III study developed to assess the efficacy of 2 topical agents used for management of acute radiation dermatitis. Female breast cancer patients who needed a course of radiation therapy in our institution were enrolled and randomized into 2 groups 1 with Mebo ointment and 1 with Biafine cream. Both medications were applied twice per day during the whole period of treatment and skin reactions and related symptoms were assessed weekly during the entire course. Grading of skin reactions was done according to the Radiation Therapy Oncology Group grading system. Results: Between September 2015 and May 2017, a total of 161 patients were recruited for this trial. Mean age was similar for both groups (50.19±12.57 vs. 51.73±11.23, respectively, P=0.41). All other patients and treatment characteristics were similar in both groups, except for the use of boost (82.7% in the Biafine group vs. 36.7% in Mebo group, P=0.012). Analysis was done for reactions recorded before the beginning of the boost and for the entire course including the boost. Using univariate and multivariate analysis, there was no significant difference in grades 2 and 3 dermatitis between the 2 groups. However, the incidence of severe pruritus and severe local skin pain were both significantly reduced in the Mebo group (14.1% in Biafine vs. 2.9% in Mebo, P=0.016 for pruritus and 11.5% vs. 1.4%, respectively, P=0.02 for severe pain). Conclusions: This study showed no difference between Mebo and Biafine in the incidence and severity of breast skin dermatitis during radiation therapy. However, the use of Mebo ointment was associated with decreased severe pruritus and pain which could positively affect patient comfort and quality of life.

A simple technique for an accurate shielding of the lungs during total body irradiation

Highlights • A total body irradiation technique based on CT simulation was newly introduced.• This technique succeeded in reducing the length of the overall treatment session.• This new technique reduced patient discomfort while ensuring accurate shielding of the lungs.

Swine Atrioventricular Node Ablation Using Stereotactic Radiosurgery: Methods and In Vivo Feasibility Investigation for Catheter‐Free Ablation of Cardiac Arrhythmias

Background Linear accelerator–based stereotactic radiosurgery delivered to cardiac arrhythmogenic foci could be a promising catheter‐free ablation modality. We tested the feasibility of in vivo atrioventricular (AV) node ablation in swine using stereotactic radiosurgery. Methods and Results Five Large White breed swine (weight 40–75 kg; 4 females) were studied. Single‐chamber St Jude pacemakers were implanted in each pig. The pigs were placed under general anesthesia, and coronary/cardiac computed tomography simulation scans were performed to localize the AV node. Cone beam computed tomography was used for target positioning. Stereotactic radiosurgery doses ranging from 35 to 40 Gy were delivered by a linear accelerator to the AV node, and the pigs were followed up with weekly pacemaker interrogations to observe for potential electrocardiographic changes. Once changes were observed, the pigs were euthanized, and pathology specimens of various tissues, including the AV node and tissues surrounding the AV node, were taken to study the effects of radiation. All 5 pigs had disturbances of AV conduction with progressive transition into complete heart block. Macroscopic inspection did not reveal damage to the myocardium, and pigs had preserved systolic function on echocardiography. Immunostaining revealed fibrosis in the target region of the AV node, whereas no fibrosis was detected in the nontargeted regions. Conclusions Catheter‐free radioablation using linear accelerator–based stereotactic radiosurgery is feasible in an intact swine model.