Nima Nabavizadeh

Percutaneous treatment of insufficiency fractures : principles, technique and review of literature.

Insufficiency fractures of the pelvis, sacrum, spine, and long bones are painful, debilitating, and are common consequences of osteoporosis. Conventional treatment for these fractures varies from conservative therapy to surgery with plate and screw fixation. The former fails to address the underlying problem of fracture and frequently does not alleviate symptoms, while the latter is invasive and not always possible in older populations with low bone density and numerous co-morbidities. Osseous augmentation with polymethylmethacrylate (PMMA) has been used for over two decades to treat fractures related to osteoporosis, but has not been commonly used to treat fractures outside of the vertebral bodies. Osseous augmentation with PMMA is an image-guided procedure and various techniques have been utilized to treat fracture in different locations. We describe various techniques for image-guided osseous augmentation and treatment of insufficiency fractures with bothPMMA and allograft bone for fractures of the pelvis including sacrum, acetabulum, pubic symphysis, pubic rami ilium; appendicular skeleton including distal radius, proximal femur, and vertebral body. We also describe the potential risks and complications associated with percutaneous treatment of insufficiency fractures and techniques to avoid the pitfalls of the various procedures. We will present the process for patient follow-up and data regarding the pre- and postprocedure pain response in patients undergoing treatment for pelvic insufficiency fractures.

Electromagnetic navigational bronchoscopy-guided fiducial markers for lung stereotactic body radiation therapy: analysis of safety, feasibility, and interfraction stability.

Background:Embolization coils as fiducial markers for pulmonary stereotactic body radiation therapy (SBRT) are perceived to be the optimal marker type, given their ability to conform and anchor within the small airways. The aim of our study was to assess retention, placement, migration, feasibility, and safety of electromagnetic navigational bronchoscopy (ENB)-guided embolization coil markers throughout courses of SBRT. Methods:Thirty-one patients with 34 nodules underwent ENB-guided fiducial placement of several 4 mm fibered platinum embolization coils before SBRT. Patient and nodule positioning was confirmed with daily pretreatment cone-beam computed tomography (CBCT). Fiducial positional characteristics were analyzed utilizing radiation treatment-planning software comparing the simulation CT with daily CBCTs. Results:Of 105 fiducials placed, 103 were identifiable on simulation CT (retention rate: 98.1%). Incidence of asymptomatic pneumothoraces was 6%. One patient experienced hemoptysis requiring hospitalization. Eighty-six percent of fiducials were placed within 1 cm of the nodule, with 52% of fiducials placed directly on the nodule surface. Throughout a 5-fraction SBRT course, fiducial displacement was <7, 5, and 2 mm in 98%, 96%, and 67% of pretreatment CBCTs. Conclusions:ENB placement of embolization coils as fiducials for lung SBRT image guidance is associated with a low rate of iatrogenic pneumothoraces, and resulted in reliable placement of the fiducials in close proximity to the lung nodule. Embolization coils retained their relative position to the nodule throughout the course of SBRT, and provide an excellent alternative to linear gold seeds.

Real-time prostate motion assessment: image-guidance and the temporal dependence of intra-fraction motion.

BackgroundThe rapid adoption of image-guidance in prostate intensity-modulated radiotherapy (IMRT) results in longer treatment times, which may result in larger intrafraction motion, thereby negating the advantage of image-guidance. This study aims to qualify and quantify the contribution of image-guidance to the temporal dependence of intrafraction motion during prostate IMRT.MethodsOne-hundred and forty-three patients who underwent conventional IMRT (n=67) or intensity-modulated arc therapy (IMAT/RapidArc, n=76) for localized prostate cancer were evaluated. Intrafraction motion assessment was based on continuous RL (lateral), SI (longitudinal), and AP (vertical) positional detection of electromagnetic transponders at 10 Hz. Daily motion amplitudes were reported as session mean, median, and root-mean-square (RMS) displacements. Temporal effect was evaluated by categorizing treatment sessions into 4 different classes: IMRTc (transponder only localization), IMRTcc (transponder + CBCT localization), IMATc (transponder only localization), or IMATcc (transponder + CBCT localization).ResultsMean/median session times were 4.15/3.99 min (IMATc), 12.74/12.19 min (IMATcc), 5.99/5.77 min (IMRTc), and 12.98/12.39 min (IMRTcc), with significant pair-wise difference (p<0.0001) between all category combinations except for IMRTcc vs. IMATcc (p>0.05). Median intrafraction motion difference between CBCT and non-CBCT categories strongly correlated with time for RMS (t-value=17.29; p<0.0001), SI (t-value=−4.25; p<0.0001), and AP (t-value=2.76; p<0.0066), with a weak correlation for RL (t-value=1.67; p=0.0971). Treatment time reduction with non-CBCT treatment categories showed reductions in the observed intrafraction motion: systematic error (Σ)<0.6 mm and random error (σ)<1.2 mm compared with ≤0.8 mm and <1.6 mm, respectively, for CBCT-involved treatment categories.ConclusionsFor treatment durations >4-6 minutes, and without any intrafraction motion mitigation protocol in place, patient repositioning is recommended, with at least the acquisition of the lateral component of an orthogonal image pair in the absence of volumetric imaging.

Topographic enhancement mapping of the cancer-associated breast stroma using breast MRI

In animal and laboratory models, cancer-associated stroma, or elements of the supporting tissue surrounding a primary tumor, has been shown to be necessary for tumor evolution and progression. However, little is understood or studied regarding the properties of intact stroma in human cancer in vivo. In addition, for breast cancer patients, the optimal volume of local tissue to treat surrounding a primary tumor is not clear. Here, we performed an interdisciplinary study of normal-appearing breast tissue using breast magnetic resonance imaging (MRI), correlative histology and array comparative genomic hybridization to identify a cancer-associated stroma in humans. Using a novel technique for segmenting breast fibroglandular tissue, quantifiable topographic percent enhancement mapping of the stroma surrounding invasive breast cancer was found to be significantly elevated within 2 cm of the tumor edge. This region was also found to harbor increased microvessel density, and genomic changes that were closely associated with host normal breast tissue. These findings indicate that a cancer-associated stroma may be identified and characterized in human breast cancer using non-invasive imaging techniques. Identification of a cancer-associated stroma may be further developed to help guide local therapy to reduce recurrence and morbidity in breast cancer patients.

Volumetric-modulated arc radiotherapy for pancreatic malignancies: dosimetric comparison with sliding-window intensity-modulated radiotherapy and 3-dimensional conformal radiotherapy.

Volumetric-modulated arc radiotherapy (VMAT) is an iteration of intensity-modulated radiotherapy (IMRT), both of which deliver highly conformal dose distributions. Studies have shown the superiority of VMAT and IMRT in comparison with 3-dimensional conformal radiotherapy (3D-CRT) in planning target volume (PTV) coverage and organs-at-risk (OARs) sparing. This is the first study examining the benefits of VMAT in pancreatic cancer for doses more than 55.8 Gy. A planning study comparing 3D-CRT, IMRT, and VMAT was performed in 20 patients with pancreatic cancer. Treatments were planned for a 25-fraction delivery of 45 Gy to a large field followed by a reduced-volume 8-fraction external beam boost to 59.4 Gy in total. OARs and PTV doses, conformality index (CI) deviations from 1.0, monitor units (MUs) delivered, and isodose volumes were compared. IMRT and VMAT CI deviations from 1.0 for the large-field and the boost plans were equivalent (large field: 0.032 and 0.046, respectively; boost: 0.042 and 0.037, respectively; p > 0.05 for all comparisons). Both IMRT and VMAT CI deviations from 1.0 were statistically superior to 3D-CRT (large field: 0.217, boost: 0.177; p < 0.05 for all comparisons). VMAT showed reduction of the mean dose to the boost PTV (VMAT: 61.4 Gy, IMRT: 62.4 Gy, and 3D-CRT: 62.3 Gy; p < 0.05). The mean number of MUs per fraction was significantly lower for VMAT for both the large-field and the boost plans. VMAT delivery time was less than 3 minutes compared with 8 minutes for IMRT. Although no statistically significant dose reduction to the OARs was identified when comparing VMAT with IMRT, VMAT showed a reduction in the volumes of the 100% isodose line for the large-field plans. Dose escalation to 59.4 Gy in pancreatic cancer is dosimetrically feasible with shorter treatment times, fewer MUs delivered, and comparable CIs for VMAT when compared with IMRT.

Association of Intervals Between Neoadjuvant Chemoradiation and Surgical Resection With Pathologic Complete Response and Survival in Patients With Esophageal Cancer.

Importance Pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (CRT) may be a clinical prognostic marker of superior outcomes. In patients with esophageal cancer, pCR is associated with increased survival. While mechanisms for increasing the likelihood of pCR remain unknown, in other solid tumors, higher rates of pCR have been associated with longer time intervals between CRT completion and surgical procedures. Objective To determine the association between time intervals from the completion of CRT to surgical procedure with rates of pCR in patients with esophageal cancer. Design, Setting, and Participants A prospectively maintained multidisciplinary foregut database was reviewed for consecutively enrolled patients with esophageal cancer from January 2000 to July 2015 presenting for surgical evaluation at a single National Cancer Institute-designated cancer center within a quaternary academic medical center. Interventions Included patients successfully completed neoadjuvant CRT followed by esophagectomy. Main Outcomes and Measures Rate of pCR by logistic regression based on a categorized time interval (ie, 0 to 42, 43 to 56, 57 to 70, 71 to 84, 85 to 98, and 99 or more days) from the completion of CRT to surgical resection, adjusted for clinical stage, demographic information, and CRT regimen. Results Of the 234 patients who met inclusion criteria, 191 (81.6%) were male, and the median (range) age was 64 (58-70) years; 206 (88.0%) were diagnosed as having adenocarcinoma, and 65 (27.9%) had a pCR. Patients in the 85 to 98-day group had significantly increased odds of a pCR compared with other groups (odds ratio, 5.46; 95% CI, 1.16-25.68; P = .03). No significant differences in survival were seen between time groups overall or among patients with residual tumor. Conclusions and Relevance This study suggests that a time interval of 85 to 98 days between CRT completion and surgical resection is associated with significantly increased odds of a pCR in patients with esophageal cancer. No adverse association with survival was detected as a result of delaying resection, even in patients with residual tumor.

Supply and Demand for Radiation Oncology in the United States: A Resident Perspective

Supply and Demand for Radiation Oncology in the United States: A Resident Perspective Lindsay M. Burt, MD,* Daniel M. Trifiletti, MD,y Nima Nabavizadeh, MD,z Leah M. Katz, MD, MPH,x Zachary S. Morris, MD, PhD,k and Trevor J. Royce, MD, MS{ *Department of Radiation Oncology, University of Utah, Salt Lake City, Utah; yDepartment of Radiation Oncology, University of Virginia, Charlottesville, Virginia; zDepartment of Radiation Medicine, Oregon Health & Science University, Portland, Oregon; xDepartment of Radiation Oncology, New York University Langone Medical Center, New York, New York; kDepartment of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin; and {Harvard Radiation Oncology Program, Harvard Medical School, Boston, Massachusetts

Preoperative carboplatin and paclitaxel-based chemoradiotherapy for esophageal carcinoma: results of a modified CROSS regimen utilizing radiation doses greater than 41.4 Gy

Trimodality therapy for resectable esophageal and gastroesophageal junction cancers utilizing preoperative radiotherapy with concurrent carboplatin and paclitaxel-based chemotherapy is being increasingly utilized secondary to the results of the phase III CROSS trial. However, there is a paucity of reports of this regimen as a component of chemoradiotherapy in North America. We aim to report on our clinical experience using a modified CROSS regimen with higher radiotherapy doses. Patients with advanced (cT2-cT4 or node positive) esophageal or gastroesophageal junction carcinoma who received preoperative carboplatin/paclitaxel-based chemoradiotherapy with radiation doses of greater than 41.4 Gray (Gy) followed by esophagectomy were identified from an institutional database. Patient, imaging, treatment, and tumor response characteristics were analyzed. Twenty-four patients were analyzed. All but one tumor had adenocarcinoma histology. The median radiation dose was 50.4 Gy. Pathologic complete response was achieved in 29% of patients, with all receiving 50.4 Gy. Three early postoperative deaths were seen, due in part to acute respiratory distress syndrome and all three patients received 50-50.4 Gy. With a median follow-up of 9.4 months (23 days-2 years), median survival was 24 months. Trimodality therapy utilizing concurrent carboplatin/paclitaxel with North American radiotherapy doses appeared to have similar pathologic complete response rates compared with the CROSS trial, but may be associated with higher toxicity. Although the sample size is small and further follow-up is necessary, radiation doses greater than 41.4 Gy may not be warranted secondary to a potentially increased risk of severe radiation-induced acute lung injury.

Neoadjuvant chemoradiotherapy with concurrent cisplatin/5-fluorouracil is associated with increased pathologic complete response and improved survival compared to carboplatin/paclitaxel in patients with locally advanced esophageal cancer.

Trimodal therapy consisting of neoadjuvant chemoradiation followed by esophagectomy has become the standard of care in North America for locally advanced esophageal cancer. While cisplatin/5-fluorouracil has been a common concurrent chemotherapy regimen since the 1980s, its utilization has declined in recent years as the Chemoradiotherapy for Oesophageal Cancer Followed by Surgery Study (CROSS) trial regimen of carboplatin/paclitaxel has become widely adopted. The efficacy of the CROSS regimen compared to alternate chemotherapy choices, however, has rarely been evaluated when each is used as a component of a trimodal treatment approach. The aim of this study is to report our institutional experience with these two concurrent chemotherapy regimens at a specialized esophageal cancer center.We performed an Institutional Review Board-approved retrospective review of a prospectively maintained institutional foregut registry from a single National Cancer Institute-designated cancer center. Esophageal cancer patients who completed trimodal therapy with a chemotherapy regimen of either carboplatin/paclitaxel or cisplatin/5-fluorouracil were identified and divided into groups based on their chemotherapy regimens. Multivariable logistic regression was used to analyze pathologic complete response rates, while the Kaplan-Meier and Cox proportional hazards models were utilized to evaluate recurrence-free and overall survival. Analytical models were adjusted for age, clinical stage, radiation dose, histologic subtype (adenocarcinoma vs. squamous cell carcinoma), and time interval from completion of neoadjuvant therapy to surgery.One hundred and forty-two patients treated between January of 2000 and July of 2015 were identified as meeting inclusion criteria. Of this group, 87 had received the CROSS regimen of carboplatin/paclitaxel, while 55 had completed cisplatin/5-fluorouracil. Multivariable analysis demonstrated that the cisplatin/5-fluorouracil.group had an increased odds of pathologic complete response (odds ratio = 2.68, 95% confidence interval, P = 0.032), as well as significantly improved recurrence-free survival (hazard ratio = 0.39, 95% confidence interval 0.21-0.73, P = 0.003) and overall survival (hazard ratio = 0.46, 95% confidence interval 0.24-0.87, P = 0.016), compared to the carboplatin/paclitaxel group.Concurrent chemotherapy with cisplatin/5-fluorouracil in locally advanced esophageal cancer is associated with higher rates of pathologic complete response and improved recurrence-free and overall survival compared to the CROSS regimen of carboplatin/paclitaxel. This suggests that, for select patients, alternate neoadjuvant chemotherapy approaches, such as cisplatin/5-fluorouracil, merit reconsideration as potential primary treatment choices in the management of this highly morbid disease.

Impact of US immigration ban on oncologists and patients: Oncology knows no borders

Recent initiatives and executive orders of the US federal administration have brought into question America’s openness to immigrants across the world who seek a successful, valued life and career in the United States. There are many personal stories of surprised and anguished clinicians, graduate students, and clinical fellows studying and working in major US health care centers who have now found themselves in a border limbo, unable to return to their new home or to have their children and family join them solely based on a heavyhanded and uninformed executive action that is both perplexing and troubling. Unbeknownst to many, this immigration and travel ban may have a disproportionate domestic impact on rural and inner-city citizens of the United States. Immigrants have historically done what no one else wants to do—and this includes providing high-quality medical care for underserved patients. As physician shortages continue in many underserved and geographically isolated regions of the United States, including an oncologist shortage projected by year 2020,1 J1 and H1B visa waivers have been a successful mechanism of bringing young, motivated, and talented physicians to practice in these regions. Many of these clinicians establish long-term practices in these underserved or isolated communities. Undoubtedly, hundreds of currently practicing physicians and physicians-in-training within these visa waiver programs are directly affected by the immigration ban, and the attractiveness of these programs to future international candidates will likely decline. Consequently, patients likely will disproportionally feel the ill effects of these policies because their care will either have to take place at greater distances or be provided by competent but short-term locum tenens physicians. In President Trump’s home state of New York in 2015, there were 477 J1sponsored physicians caring for hundreds of thousands of patients,2 and although most were not from the countries with travel restrictions, these physicians across primary care and specialty clinics will likely have a more pessimistic outlook on their future and acceptance in the United States regardless of their country of origin. To be clear, this will have an impact on all states. We seek to affirm our commitment to more (not less) diversity and inclusion as it pertains to multifaceted missions of patient care, research, teaching, and community service. We believe that the potential ramifications of these policies are substantial. Oncology is enriched with a diverse mix of male and female clinicians and scientific investigators from all different ethnicities, races, and religious views. Furthermore, the promulgation of ideas through international conferences (many of which take place in the United States) is a major priority within our field, and the uncertainty of cross-border travel in 2017 will surely have a negative impact on future international collaborations and dissemination of research, new techniques, and potentially life-saving therapies. Upward of one-third of attendees of some of the major oncology subspecialty meetings are from international institutions, and under the current travel restrictions, most could legally travel to the United States. However, if our current (and potential future) colleagues from outside the United States are reluctant to travel to this country, our specialty and others will suffer. The possible fluidity of these executive actions to better align with preinauguration campaign pledges of exclusion based more widely on religious views and ethnic background echoes other regretful times in this country’s 238-year history. Oncologists in particular and physicians in general occupy a special place in the US social conscience, and we must use this platform to advocate for the respect of people affected by these unusual, yet oftrepeated, circumstances. These first few weeks of the new administration must not detract from one of the most primary motivations of being a physician: compassion. Moving forward in 2017, as oncologists we must find a way to constructively adapt and support our colleagues and patients who may be personally affected by bigotry or racism.3 Regrettably, patients with terminal illnesses who have loved ones in countries included in the ban face an impossible decision—whether to continue to receive lifepreserving therapies or forfeit all of it to see a loved one for a last time. Such choices are unwarranted. As Dr Martin Luther King Jr described in his “I Have a Dream...” speech, our freedom is inextricably bound by their freedom.