Publications by authors named "Kujtim Latifi"

47 Publications

Non-Adaptive MR-Guided Radiotherapy for Prostate SBRT: Less Time, Equal Results.

J Clin Med 2021 Jul 30;10(15). Epub 2021 Jul 30.

Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.

Background: The use of stereotactic body radiation therapy (SBRT) is widely utilized for treatment of localized prostate cancer. Magnetic-resonance-guided radiotherapy (MRgRT) was introduced in 2014 and has recently been implemented in SBRT for prostate cancer as it provides an opportunity for smaller margins and adaptive daily planning. Currently, the only publications of MRgRT for prostate SBRT describe European clinical experiences which utilized adaptive planning. However, adaptive planning adds significantly to the time required for daily treatment.

Objectives: Since prostate SBRT has demonstrated acceptable toxicity for several years, we did not consider daily adaptation critical to the process of prostate SBRT. After Institutional Review Board approval, we analyzed and now report our experience using MRgRT without adaptation.

Methods: Between 25 September 2019 and 21 December 2020, 35 consecutive patients were treated with MRgRT prostate SBRT at our center. Patients treated with MRgRT included favorable intermediate risk (43%) and unfavorable intermediate risk (54%), and only one patient had low-risk prostate cancer. Nine patients (25%) received adjuvant leuprolide for a median of 4.5 months (range 4-6 m). Our clinical pathway allows for a maximum prostate gland volume of 60 cc; median prostate volume of this cohort was 35.0 cc (range 17-58.4 cc). Median pre-treatment PSA was 6.30 (range 2.55-16.77). Each patient was treated with 36.25 Gy delivered in five fractions over 2 weeks with urethral sparing to a maximal dose of 35 Gy. Target volumes included the prostate gland and proximal seminal vesicles with a 3 mm margin.

Results: Median follow-up as of 26 May 2021 was 11.97 months (range 4.37-19.80). First follow-up data are available for all patients, with a median of 1.10 month from completion of treatment (0.63-3.40). The median PSA at first visit was 2.75 (range 0.02-9.00) with a median AUA symptom score of 9 (range 1-24). Second follow-up data are available for 34 patients at a median of 4.45 months (range 2.57-8.90). At second follow-up, the median PSA was 1.60 (range 0.02-5.40) with a median AUA symptom score of 6 (range 1-33). Seventeen patients had third follow-up data with a median of 9.77 months (range 4.70-12.33) after SBRT. The median PSA was 1.13 (range 0.02-4.73) with an AUA score of 9 (2-22) at the third follow-up. We observed a statistically significant decrease in PSA between pre-treatment and at first follow-up ( < 0.005). The most common toxicity was grade 2 urethritis, managed in all cases by tamsulosin. One patient developed grade 2 tenesmus relieved by topical steroids. No cases of grade ≥ 3 toxicity were seen in our patient population.

Conclusions: By avoiding the extra time required for plan adaptation, MRgRT without daily adaptation allows for successful prostate SBRT with manageable toxicity. We continue to reserve our limited adaptive treatment slots for preoperative pancreatic and ultra-central lung SBRT patients, which require time-intensive respiratory gating and adaptive planning.
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http://dx.doi.org/10.3390/jcm10153396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8347281PMC
July 2021

On the MLC leaves alignment in the direction orthogonal to movement.

J Appl Clin Med Phys 2021 Jun 30;22(6):268-273. Epub 2021 May 30.

Department of Radiation Oncology, Moffitt Cancer Center, Tampa, FL, USA.

The main focus of the recommended spatial accuracy tests for the multi-leaf collimators (MLC) is calibration of the leaf position along the movement direction and overall alignment to the radiation isocenter. No explicit attention was typically paid to the alignment of the leaves from the opposing banks in the direction orthogonal to movement. This paper is a case study demonstrating that verification of such alignment at the time of acceptance testing is prudent. The original standard MLC (SMLC) on an MRIdian MRI-guided linac (ViewRay Inc., Mountain View, CA, USA) was upgraded to a high-speed MLC (HSMLC), which is supposed to be mechanically identical to the SMLC except for the higher drive screw pitch. The results of the end-to-end IMRT tests demonstrated unacceptable dosimetric results exemplified by an average and maximum ion chamber (IC) point dose error in the high-dose low-gradient region of 2.5 ± 1.4% and 4.6%, respectively. Before the upgrade, those values were 0.3 ± 0.7% and 0.9%, respectively. An exhaustive analysis of possible failure modes eventually zeroed in on the average misalignment of about 1 mm in the Y (along the couch) direction between the right and left upper MLC banks. The MLC was replaced, reducing the Y-direction misalignment to 0.4 mm. As a result, the average and maximum IC dose-errors became acceptable 1.0 ± 0.7% and 1.6%, respectively. Simple film and/or chamber array tests during acceptance testing can easily detect Y-direction misalignments between opposing leaves banks measuring a fraction of a mm at isocenter. Left undetected, such misalignment can cause nontrivial dosimetric consequences.
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http://dx.doi.org/10.1002/acm2.13267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200498PMC
June 2021

Gonadal-sparing total body irradiation with the use of helical tomotherapy for nonmalignant indications.

Rep Pract Oncol Radiother 2021 25;26(1):153-158. Epub 2021 Feb 25.

Department of Radiation Oncology, H. Lee Moffit Cancer Center and Research Institute, Tampa, FL, United States.

Background: The aim was to demonstrate the feasibility and technique of gonadal sparing total body irradiation (TBI) with helical tomotherapy. Total body irradiation is a common part of the conditioning regimen prior to allogeneic stem cell transplantation. Shielding or dose-reduction to the gonads is often desired to preserve fertility, particularly in young patients undergoing transplant for non-malignant indications. Helical tomotherapy (HT) has been shown to be superior to traditional TBI delivery for organ at risk (OA R) doses and dose homogeneity.

Materials And Methods: We present two representative cases (one male and one female) to illustrate the feasibility of this technique, each of whom received 3Gy in a single fraction prior to allogeneic stem cell transplant for benign indications. The planning target volume (PTV) included the whole body with a subtraction of OA Rs including the lungs, heart, and brain (each contracted by 1cm) as well as the gonads (testicles expanded by 5 cm and ovaries expanded by 0.5 cm).

Results: For the male patient we achieved a homogeneity index of 1.35 with a maximum and median planned dose to the testes of 0.53 Gy and 0.35 Gy, respectively. In-vivo dosimetry demonstrated an actual received dose of 0.48 Gy. For the female patient we achieved a homogeneity index of 1.13 with a maximum and median planned dose to the ovaries of 1.66 Gy and 0.86 Gy, respectively.

Conclusion: Gonadal sparing TBI is feasible and deliverable using HT in patients with non-malignant diseases requiring TBI as part of a pre-stem cell transplant conditioning regimen.
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http://dx.doi.org/10.5603/RPOR.a2021.0006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149136PMC
February 2021

Pretreatment CT and PET radiomics predicting rectal cancer patients in response to neoadjuvant chemoradiotherapy.

Rep Pract Oncol Radiother 2021 25;26(1):29-34. Epub 2021 Feb 25.

Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida, United States.

Background: The purpose of this study was to characterize pre-treatment non-contrast computed tomography (CT) and F-fluorodeoxyglucose positron emission tomography (PET) based radiomics signatures predictive of pathological response and clinical outcomes in rectal cancer patients treated with neoadjuvant chemoradiotherapy (NACR T).

Materials And Methods: An exploratory analysis was performed using pre-treatment non-contrast CT and PET imaging dataset. The association of tumor regression grade (TRG) and neoadjuvant rectal (NAR) score with pre-treatment CT and PET features was assessed using machine learning algorithms. Three separate predictive models were built for composite features from CT + PET.

Results: The patterns of pathological response were TRG 0 (n = 13; 19.7%), 1 (n = 34; 51.5%), 2 (n = 16; 24.2%), and 3 (n = 3; 4.5%). There were 20 (30.3%) patients with low, 22 (33.3%) with intermediate and 24 (36.4%) with high NAR scores. Three separate predictive models were built for composite features from CT + PET and analyzed separately for clinical endpoints. Composite features with α = 0.2 resulted in the best predictive power using logistic regression. For pathological response prediction, the signature resulted in 88.1% accuracy in predicting TRG 0 . TRG 1-3; 91% accuracy in predicting TRG 0-1 . TRG 2-3. For the surrogate of DFS and OS, it resulted in 67.7% accuracy in predicting low . intermediate . high NAR scores.

Conclusion: The pre-treatment composite radiomics signatures were highly predictive of pathological response in rectal cancer treated with NACR T. A larger cohort is warranted for further validation.
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http://dx.doi.org/10.5603/RPOR.a2021.0004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086711PMC
February 2021

Rigid and Deformable Image Registration for Radiation Therapy: A Self-Study Evaluation Guide for NRG Oncology Clinical Trial Participation.

Pract Radiat Oncol 2021 Jul-Aug;11(4):282-298. Epub 2021 Mar 2.

Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania.

Purpose: The registration of multiple imaging studies to radiation therapy computed tomography simulation, including magnetic resonance imaging, positron emission tomography-computed tomography, etc. is a widely used strategy in radiation oncology treatment planning, and these registrations have valuable roles in image guidance, dose composition/accumulation, and treatment delivery adaptation. The NRG Oncology Medical Physics subcommittee formed a working group to investigate feasible workflows for a self-study credentialing process of image registration commissioning.

Methods And Materials: The American Association of Physicists in Medicine (AAPM) Task Group 132 (TG132) report on the use of image registration and fusion algorithms in radiation therapy provides basic guidelines for quality assurance and quality control of the image registration algorithms and the overall clinical process. The report recommends a series of tests and the corresponding metrics that should be evaluated and reported during commissioning and routine quality assurance, as well as a set of recommendations for vendors. The NRG Oncology medical physics subcommittee working group found incompatibility of some digital phantoms with commercial systems. Thus, there is still a need to provide further recommendations in terms of compatible digital phantoms, clinical feasible workflow, and achievable thresholds, especially for future clinical trials involving deformable image registration algorithms. Nine institutions participated and evaluated 4 commonly used commercial imaging registration software and various versions in the field of radiation oncology.

Results And Conclusions: The NRG Oncology Working Group on image registration commissioning herein provides recommendations on the use of digital phantom/data sets and analytical software access for institutions and clinics to perform their own self-study evaluation of commercial imaging systems that might be employed for coregistration in radiation therapy treatment planning and image guidance procedures. Evaluation metrics and their corresponding values were given as guidelines to establish practical tolerances. Vendor compliance for image registration commissioning was evaluated, and recommendations were given for future development.
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http://dx.doi.org/10.1016/j.prro.2021.02.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8406084PMC
September 2021

Pretreatment CT and F-FDG PET-based radiomic model predicting pathological complete response and loco-regional control following neoadjuvant chemoradiation in oesophageal cancer.

J Med Imaging Radiat Oncol 2021 Feb 1;65(1):102-111. Epub 2020 Dec 1.

Department of Radiation Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida, USA.

Introduction: To develop a radiomic-based model to predict pathological complete response (pCR) and outcome following neoadjuvant chemoradiotherapy (NACRT) in oesophageal cancer.

Methods: We analysed 68 patients with oesophageal cancer treated with NACRT followed by esophagectomy, who had staging 18F-fluorodeoxyglucose ( F-FDG) positron emission tomography (PET) and computed tomography (CT) scans performed at our institution. An in-house data-chjmirocterization algorithm was used to extract 3D-radiomic features from the segmented primary disease. Prediction models were constructed and internally validated. Composite feature, F  = α * F  + (1 - α) * F , 0 ≤ α ≤ 1, was constructed for each corresponding CT and PET feature. Loco-regional control (LRC), recurrence-free survival (RFS), metastasis-free survival (MFS) and overall survival (OS) were estimated by Kaplan-Meier analysis, and compared using log-rank test.

Results: Median follow-up was 59 months. pCR was achieved in 34 (50%) patients. Five-year RFS, LRC, MFS and OS were 67.1%, 88.5%, 75.6% and 57.6%, respectively. Tumour Regression Grade (TRG) 0-1 indicative of complete response or minimal residual disease was significantly associated with improved 5-year LRC [93.7% vs 71.8%; P = 0.020; HR 0.19, 95% CI 0.04-0.85]. Four sepjmirote pCR predictive models were built for CT alone, PET alone, CT+PET and composite. CT, PET and CT+PET models had AUC 0.73 ± 0.08, 0.66 ± 0.08 and 0.77 ± 0.07, respectively. The composite model resulted in an improvement of pCR predicting power with AUC 0.87 ± 0.06. Stratifying patients with a low versus high radiomic score showed clinically relevant improvement in 5-year LRC favouring low-score group (91.1% vs. 80%, 95% CI 0.09-1.77, P = 0.2).

Conclusion: The composite CT/PET radiomics model was highly predictive of pCR following NACRT. Validation in larger data sets is warranted to determine whether the model can predict clinical outcomes.
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http://dx.doi.org/10.1111/1754-9485.13128DOI Listing
February 2021

MR-guided stereotactic body radiation therapy for intracardiac and pericardial metastases.

Clin Transl Radiat Oncol 2020 Nov 31;25:102-106. Epub 2020 Oct 31.

Department of Radiation Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, United States.

Aims: To assess the safety and efficacy of MR-guided stereotactic body radiation therapy (MRgSBRT) for cardiac metastases.

Materials/methods: This single institution retrospective analysis evaluated our experience with MRgSBRT for cardiac metastases. Response rate was compared between pre-RT and post-RT imaging. Symptomatic changes were also tracked and documented.

Results: Between 4/2019 and 3/2020, five patients with cardiac metastases (4 intracardiac and 1 pericardial) were treated with MRgSBRT. Median age at treatment was 73 years (range 64-80) and two patients had pre-existing cardiac disease. Histologies included melanoma and breast adenocarcinoma. Median lesion diameter was 2 cm (range 1.96-5.8 cm). Three patients were symptomatic, one of whom had pulmonary hypertension and RV enlargement. Another patient had an asymptomatic arrythmia. Median PTV prescribed dose was 40 Gy (range 40-50 Gy) and delivered in five fractions on nonconsecutive days. Median PTV volume was 53.4 cc (range 8.7-116.6 cc) and median coverage was 95% (range 84.1-100%). A uniform 3 mm margin was used for real-time gating, allowing a median 7% (range 5-10%) pixel excursion tolerance. Median follow-up was 4.7 months (range 0.9-12.3). Two patients exhibited stable disease, two had a partial response and one exhibited a complete response. All symptomatic patients experienced some relief. There were no acute adverse events, however, one patient without prior cardiac disease developed atrial fibrillation 6 months after treatment. Two patients died of causes unrelated to cardiac MRgSBRT.

Conclusion: In this largest known series of cardiac metastasis MRgSBRT, real-time image guidance enables safe treatment resulting in good response with improving presenting symptoms without acute adverse events.
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http://dx.doi.org/10.1016/j.ctro.2020.10.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653008PMC
November 2020

Magnetic Resonance Guided Radiotherapy for Rectal Cancer: Expanding Opportunities for Non-Operative Management.

Cancer Control 2020 Jan-Dec;27(1):1073274820969449

Department of Radiation Oncology, Miami Cancer Institute, Miami, FL, USA.

Colorectal cancer is the third most common cancer in men and the second most common in women worldwide, and the incidence is increasing among younger patients. 30% of these malignancies arise in the rectum. Patients with rectal cancer have historically been managed with preoperative radiation, followed by radical surgery, and adjuvant chemotherapy, with permanent colostomies in up to 20% of patients. Beginning in the early 2000s, non-operative management (NOM) of rectal cancer emerged as a viable alternative to radical surgery in select patients. Efforts have been ongoing to optimize neoadjuvant therapy for rectal cancer, thereby increasing the number of patients potentially eligible to forgo radical surgery. Magnetic resonance guided radiotherapy (MRgRT) has recently emerged as a treatment modality capable of intensifying preoperative radiation therapy for rectal cancer patients. This technology may also predict which patients will achieve a complete response to preoperative therapy, thereby allowing for more appropriate selection of patients for NOM. The present work seeks to illustrate the potential role MRgRT could play in personalizing rectal cancer treatment thus expanding the role of NOM in rectal cancer.
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http://dx.doi.org/10.1177/1073274820969449DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791447PMC
July 2021

Prospective Single-Arm Phase 1 and 2 Study: Ipilimumab and Nivolumab With Thoracic Radiation Therapy After Platinum Chemotherapy in Extensive-Stage Small Cell Lung Cancer.

Int J Radiat Oncol Biol Phys 2021 02 28;109(2):425-435. Epub 2020 Sep 28.

Department of Medical Oncology, Duke Cancer Institute, Duke University Medical Center.

Purpose: Consolidative thoracic radiation therapy (TRT) has been shown to improve outcomes for patients with extensive stage small cell lung cancer. We hypothesized that the addition of ipilimumab (IPI) and nivolumab (NIVO) after TRT would improve outcomes for patients with extensive stage small cell lung cancer.

Methods And Materials: Eligibility required stable disease or better after platinum doublet chemotherapy. Study therapy included consolidative TRT to 30 Gy in 10 fractions, targeting residual primary tumor and initially involved regional lymph nodes. Two weeks after TRT, patients received concurrent IPI (3 mg/kg) and NIVO (1 mg/kg) every 3 weeks for 4 doses followed by NIVO monotherapy (480 mg) every 4 weeks until progression or up to 1 year.

Results: The study enrolled 21 patients, with 6-month progression-free survival (PFS) of 24% (90% confidence interval [CI], 11%-40%) and a median PFS of 4.5 months (95% CI, 2.7%-4.6%). The 12-month overall survival (OS) was 48% (95% CI, 29%-64%) with a median OS of 11.7 months (95% CI, 4.7%-16.0%). Fifty-two percent of patients had ≥1 possibly related grade 3 to 4 immune-related adverse event. Grade 3 pulmonary and gastrointestinal immune-related adverse events were recorded in 19% and 24% of patients, respectively. Exploratory analysis showed increased cytotoxic T cell (CD3+CD8+) tumor infiltration was associated with favorable PFS (P = .01) and OS (P = .02). Reduction in peripheral blood CD3+CD8+ from baseline to after first dose of IPI/NIVO was associated with improved PFS (P = .02) and OS (P = .02).

Conclusions: Consolidative IPI and NIVO after platinum-based chemotherapy and TRT demonstrated a toxicity profile consistent with the known adverse events attributable to IPI and NIVO. Although the study regimen did not significantly improve PFS, the OS was higher than historic expectations. CD3+CD8+ tumor infiltration and migration may identify patients most likely to have improved outcomes in small cell lung cancer.
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http://dx.doi.org/10.1016/j.ijrobp.2020.09.031DOI Listing
February 2021

Proof-of-principle Phase I results of combining nivolumab with brachytherapy and external beam radiation therapy for Grade Group 5 prostate cancer: safety, feasibility, and exploratory analysis.

Prostate Cancer Prostatic Dis 2021 03 10;24(1):140-149. Epub 2020 Jul 10.

Departments of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA.

Background: To determine whether combining brachytherapy with immunotherapy is safe in prostate cancer (PCa) and provides synergistic effects, we performed a Phase I/II trial on the feasibility, safety, and benefit of concurrent delivery of anti-PD-1 (nivolumab) with high-dose-rate (HDR) brachytherapy and androgen deprivation therapy (ADT) in patients with Grade Group 5 (GG5) PCa.

Methods: Eligible patients were aged 18 years or older with diagnosis of GG5 PCa. Patients received ADT, nivolumab every two weeks for four cycles, with two cycles prior to first HDR, and two more cycles prior to second HDR, followed by external beam radiotherapy. The primary endpoint was to determine safety and feasibility. This Phase I/II trial is registered with ClinicalTrials.gov (NCT03543189).

Results: Between September 2018 and June 2019, six patients were enrolled for the Phase I safety lead-in with a minimum observation period of 3 months after nivolumab administration. Overall, nivolumab was well tolerated in combination with ADT and HDR treatment. One patient experienced a grade 3 dose-limiting toxicity (elevated Alanine aminotransferase and Aspartate aminotransferase) after the second cycle of nivolumab. Three patients (50%) demonstrated early response with no residual tumor detected in ≥4 of 6 cores on biopsy post-nivolumab (4 cycles) and 1-month post-HDR. Increase in CD8+ and FOXP3+/CD4+ T cells in tissues, and CD4+ effector T cells in peripheral blood were observed in early responders.

Conclusion: Combination of nivolumab with ADT and HDR is well tolerated and associated with evidence of increased immune infiltration and antitumor activity.
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http://dx.doi.org/10.1038/s41391-020-0254-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882397PMC
March 2021

Rare Abdominal Wall Metastasis following Curative Resection of Gastric Cancer: What Can Be Learned from the Use of Percutaneous Catheters?

Case Rep Oncol Med 2020 9;2020:3738798. Epub 2020 May 9.

Department of Radiology, Moffitt Cancer Center, Tampa, Florida, USA.

In cancer care, tissue seeding after curative resections is a known potential complication, despite precautions taken during surgical treatment. We present an uncommon case of an abdominal wall metastasis along the tract of a surgical drain following gastrectomy for gastric adenocarcinoma. To our knowledge, this is the first case of such an occurrence in the setting of a negative staging peritoneal lavage. Aside from the rarity of such a recurrence, this instance highlights an opportunity to reevaluate best practices with regard to the extent of coverage of postoperative salvage radiotherapy. The oncologic patient provides many challenges and may require multiple catheters for drainage and at times infusion of nutrition or therapeutic agents. These foreign bodies should be scrutinized both clinically and radiographically, as they may create vulnerabilities in keeping malignant diseases contained and controlled. We provide a review of the literature with reasonable treatment options for the benefit of future patients.
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http://dx.doi.org/10.1155/2020/3738798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7244962PMC
May 2020

CT-based radiomic features to predict pathological response in rectal cancer: A retrospective cohort study.

J Med Imaging Radiat Oncol 2020 Jun 9;64(3):444-449. Epub 2020 May 9.

Radiation Oncology, Moffitt Cancer Center, Tampa, Florida, USA.

Introduction: Innovative biomarkers to predict treatment response in rectal cancer would be helpful in optimizing personalized treatment approaches. In this study, we aimed to develop and validate a CT-based radiomic imaging biomarker to predict pathological response.

Methods: We used two independent cohorts of rectal cancer patients to develop and validate a CT-based radiomic imaging biomarker predictive of treatment response. A total of 91 rectal cancer cases treated from 2009 to 2018 were assessed for the tumour regression grade (TRG) (0 = pathological complete response, pCR; 1 = moderate response; 2 = partial response; 3 = poor response). Exploratory analysis was performed by combining pre-treatment non-contrast CT images and patterns of TRG. The models built from the training cohort were further assessed using the independent validation cohort.

Results: The patterns of pathological response in training and validation groups were TRG 0 (n = 14, 23.3%; n = 6, 19.4%), 1 (n = 31, 51.7%; n = 15, 48.4%), 2 (n = 12, 20.0%; n = 7, 22.6%) and 3 (n = 3, 5.0%; n = 3, 9.7%), respectively. Separate predictive models were built and analysed from CT features for pathological response. For pathological response prediction, the model including 8 radiomic features by random forest method resulted in 83.9% accuracy in predicting TRG 0 vs TRG 1-3 in validation.

Conclusion: The pre-treatment CT-based radiomic signatures were developed and validated in two independent cohorts. This imaging biomarker provided a promising way to predict pCR and select patients for non-operative management.
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http://dx.doi.org/10.1111/1754-9485.13044DOI Listing
June 2020

Radiation-induced hepatitis masquerading as metastatic disease: the importance of correlating diagnostic imaging with treatment planning.

J Gastrointest Oncol 2020 Feb;11(1):133-138

Department of Radiation Oncology, Moffitt Cancer Center, Tampa, FL, USA.

We are presenting a 63-year-old Caucasian male who complained of 2 months of progressive dysphagia. Upper endoscopy discovered a mass in the distal esophagus near the gastroesophageal junction. Biopsy was consistent with adenocarcinoma. Endoscopic ultrasound (EUS) showed extension beyond the muscularis propria, with an enlarged paraesophageal lymph node (T3N1). Initial positron emission tomography (PET)/computed tomography (CT) showed hypermetabolic portocaval lymphadenopathy presumed to be metastatic, but otherwise without distant disease extension. Neoadjuvant treatment included induction FOLFOX followed by 5,600 cGy over 28 fractions in combination with 5-FU and oxaliplatin. Approximately 3.5 weeks after completion, a repeat PET/CT revealed reduced uptake in both the primary esophageal mass and regional lymph nodes. Of note there were several new mass-like foci of hypermetabolism in the liver, specifically the left lobe, concerning for metastatic disease. Image-guided biopsy did not show any identifiable lesions, but sampling was performed based on anatomical landmarks. Pathology revealed benign parenchyma with minimal inflammation and mild reactive regeneration. In light of this, the patient proceeded to undergo definitive resection via robotic Ivor-Lewis esophagectomy with only 1 positive lymph node. Given pleural involvement by the tumor, staging was revised to pT4aN1 with final histology characterized as adenosquamous carcinoma. Postoperative course was fairly uneventful, with a mild exacerbation of his chronic heart failure. The patient was discharged on post-operative day 7, with his feeding tube removed at his 2-week post-operative clinic visit. This scenario is of particular educational value from the standpoint that when the post-treatment PET/CT images are registered to the radiotherapy treatment planning CT and dose, the areas of abnormal uptake in the liver fall within the higher dose regions. Given this and the liver biopsy findings, caution should be exercised before declaring progressive disease following radiotherapy without first reviewing the treatment plan.
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http://dx.doi.org/10.21037/jgo.2019.09.09DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052759PMC
February 2020

Prediction of Anal Cancer Recurrence After Chemoradiotherapy Using Quantitative Image Features Extracted From Serial F-FDG PET/CT.

Front Oncol 2019 27;9:934. Epub 2019 Sep 27.

Department of Radiation Oncology, University of Maryland Baltimore, Baltimore, MD, United States.

We extracted image features from serial F-labeled fluorodeoxyglucose (FDG) positron emission tomography (PET) / computed tomography (CT) scans of anal cancer patients for the prediction of tumor recurrence after chemoradiation therapy (CRT). Seventeen patients (4 recurrent and 13 non-recurrent) underwent three PET/CT scans at baseline (Pre-CRT), in the middle of the treatment (Mid-CRT) and post-treatment (Post-CRT) were included. For each patient, Mid-CRT and Post-CRT scans were aligned to Pre-CRT scan. Comprehensive image features were extracted from CT and PET (SUV) images within manually delineated gross tumor volume, including geometry features, intensity features and texture features. The difference of feature values between two time points were also computed and analyzed. We employed univariate logistic regression model, multivariate model, and naïve Bayesian classifier to analyze the image features and identify useful tumor recurrent predictors. The area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the accuracy of the prediction. In univariate analysis, six geometry, three intensity, and six texture features were identified as significant predictors of tumor recurrence. A geometry feature of Roundness between Post-CRT and Pre-CRT CTs was identified as the most important predictor with an AUC value of 1.00 by multivariate logistic regression model. The difference of Number of Pixels on Border (geometry feature) between Post-CRT and Pre-CRT SUVs and Elongation (geometry feature) of Post-CRT CT were identified as the most useful feature set (AUC = 1.00) by naïve Bayesian classifier. To investigate the early prediction ability, we used features only from Pre-CRT and Mid-CRT scans. Orientation (geometry feature) of Pre-CRT SUV, Mean (intensity feature) of Pre-CRT CT, and Mean of Long Run High Gray Level Emphasis (LRHGLE) (texture feature) of Pre-CRT CT were identified as the most important feature set (AUC = 1.00) by multivariate logistic regression model. Standard deviation (intensity feature) of Mid-CRT SUV and difference of Mean of LRHGLE (texture feature) between Mid-CRT and Pre-CRT SUVs were identified as the most important feature set (AUC = 0.86) by naïve Bayesian classifier. The experimental results demonstrated the potential of serial PET/CT scans in early prediction of anal tumor recurrence.
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http://dx.doi.org/10.3389/fonc.2019.00934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6777412PMC
September 2019

A Method to Determine the Coincidence of MRI-Guided Linac Radiation and Magnetic Isocenters.

Technol Cancer Res Treat 2019 01;18:1533033819877986

Department of Radiation Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, USA.

To assure accurate treatment delivery on any image-guided radiotherapy system, the relative positions and walkout of the imaging and radiation isocenters must be periodically verified and kept within specified tolerances. In this work, we first validated the multiaxis ion chamber array as a tool for finding the radiation isocenter position of a magnetic resonance-guided linear accelerator. The treatment couch with the array on it was shifted in 0.2-mm increments and the reported beam center position was plotted against that shift and fitted to a straight line, in both X and Y directions. From the goodness-of-fit and intercepts of the regression lines, the accuracy and precision were conservatively estimated at 0.2 and 0.1 mm, respectively. This holds true whether the array is irradiated from the front or from the back, which allows efficient collecting the data from the 4 cardinal gantry angles with just 2 array positions. The average isocenter position agreed to within at most 0.4 mm along any cardinal axis with the linac vendor's film-based procedure, and the maximum walkout radii were 0.32 mm and 0.53 mm, respectively. The magnetic resonance imaging isocenter walkout as a function of gantry angle was studied with 2 different phantoms, one employing a single fiducial at the center and another extracting the rigid displacement values from the distortion map fit of 523 fiducials dispersed over a large volume. The results were close between the 2 phantoms and demonstrated variation in the magnetic resonance imaging isocenter location as high as 1.3 mm along a single axis in the transverse plane. Verification of the magnetic resonance imaging isocenter location versus the gantry angle should be a part of quality assurance for magnetic resonance-guided linear accelerators.
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http://dx.doi.org/10.1177/1533033819877986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6755638PMC
January 2019

Recognition of Tumor Invasion of a Pancreatic Head Biliary Stent During Stereotactic Body Radiation Therapy.

Pract Radiat Oncol 2019 May 29;9(3):132-135. Epub 2019 Jan 29.

Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida.

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http://dx.doi.org/10.1016/j.prro.2019.01.008DOI Listing
May 2019

Radiotherapy for Hepatocellular Carcinoma in Russia: a Survey-Based Analysis of Current Practice and the Impact of an Educational Workshop on Clinical Expertise.

J Cancer Educ 2020 02;35(1):105-111

International Design and Implementation Group for Radiation Oncology workshops (INDIGO), Moscow, Russia.

Radiation therapy (RT) is an effective treatment modality for hepatocellular carcinoma (HCC), but globally, it is underutilized. In Russia, practice patterns with regard to liver-directed radiation are unknown. Under the auspices of Russian Society of Clinical Oncology (RUSSCO), our team conducted an IRB-approved contouring workshop for Russian radiation oncologists. Pre- and post-workshop surveys were analyzed to determine baseline clinical experience and patterns of care for liver-directed RT among Russian providers. The effect of the contouring workshop on participants' knowledge was tested using mixed effects model. Forty pre-workshop and 24 post-workshop questionnaires were analyzable with a 100% response rate. Sixty percent of respondents had never evaluated a patient with HCC and only 8% (3 out of 40) reported treating an HCC patient with liver-directed RT. Nonetheless, 73% of respondents were comfortable offering liver-directed RT prior to the workshop. After the workshop, 85% of respondents felt comfortable treating a patient with HCC with liver-directed RT and 50% were comfortable recommending stereotactic body radiation therapy (SBRT). Measures of knowledge pertaining to evaluation of HCC patients and selection for appropriate liver-directed therapies were dramatically improved after the workshop. Liver-directed RT is not commonly used in Russia in the management of patients with HCC, and few centers are equipped for motion management. Our contouring workshop resulted in dramatically improved understanding of the evaluation and management of HCC patients. We recommend starting with a more protracted fractionated RT and building experience through attendance of additional educational activities, participation in multidisciplinary liver tumor boards, and prospective analysis of treatment toxicity and outcomes.
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http://dx.doi.org/10.1007/s13187-018-1447-0DOI Listing
February 2020

Voxel size and gray level normalization of CT radiomic features in lung cancer.

Sci Rep 2018 Jul 12;8(1):10545. Epub 2018 Jul 12.

Department of Physics, University of South Florida, Tampa, FL, 33620, USA.

Radiomic features are potential imaging biomarkers for therapy response assessment in oncology. However, the robustness of features with respect to imaging parameters is not well established. Previously identified potential imaging biomarkers were found to be intrinsically dependent on voxel size and number of gray levels (GLs) in a recent texture phantom investigation. Here, we validate the voxel size and GL in-phantom normalizations in lung tumors. Eighteen patients with non-small cell lung cancer of varying tumor volumes were analyzed. To compare with patient data, phantom scans were acquired on eight different scanners. Twenty four previously identified features were extracted from lung tumors. The Spearman rank (r) and interclass correlation coefficient (ICC) were used as metrics. Eight out of 10 features showed high (r > 0.9) and low (r < 0.5) correlations with number of voxels before and after normalizations, respectively. Likewise, texture features were unstable (ICC < 0.6) and highly stable (ICC > 0.8) before and after GL normalizations, respectively. We conclude that voxel size and GL normalizations derived from a texture phantom study also apply to lung tumors. This study highlights the importance and utility of investigating the robustness of radiomic features with respect to CT imaging parameters in radiomic phantoms.
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http://dx.doi.org/10.1038/s41598-018-28895-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6043486PMC
July 2018

Practical quantification of image registration accuracy following the AAPM TG-132 report framework.

J Appl Clin Med Phys 2018 Jul 7;19(4):125-133. Epub 2018 Jun 7.

Department of Radiation Oncology, Moffitt Cancer Center, Tampa, FL, USA.

The AAPM TG 132 Report enumerates important steps for validation of the medical image registration process. While the Report outlines the general goals and criteria for the tests, specific implementation may be obscure to the wider clinical audience. We endeavored to provide a detailed step-by-step description of the quantitative tests' execution, applied as an example to a commercial software package (Mirada Medical, Oxford, UK), while striving for simplicity and utilization of readily available software. We demonstrated how the rigid registration data could be easily extracted from the DICOM registration object and used, following some simple matrix math, to quantify accuracy of rigid translations and rotations. The options for validating deformable image registration (DIR) were enumerated, and it was shown that the most practically viable ones are comparison of propagated internal landmark points on the published datasets, or of segmented contours that can be generated locally. The multimodal rigid registration in our example did not always result in the desired registration error below ½ voxel size, but was considered acceptable with the maximum errors under 1.3 mm and 1°. The DIR target registration errors in the thorax based on internal landmarks were far in excess of the Report recommendations of 2 mm average and 5 mm maximum. On the other hand, evaluation of the DIR major organs' contours propagation demonstrated good agreement for lung and abdomen (Dice Similarity Coefficients, DSC, averaged over all cases and structures of 0.92 ± 0.05 and 0.91 ± 0.06, respectively), and fair agreement for Head and Neck (average DSC = 0.73 ± 0.14). The average for head and neck is reduced by small volume structures such as pharyngeal constrictor muscles. Even these relatively simple tests show that commercial registration algorithms cannot be automatically assumed sufficiently accurate for all applications. Formalized task-specific accuracy quantification should be expected from the vendors.
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http://dx.doi.org/10.1002/acm2.12348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6036411PMC
July 2018

Investigating multi-radiomic models for enhancing prediction power of cervical cancer treatment outcomes.

Phys Med 2018 Feb 21;46:180-188. Epub 2018 Feb 21.

H. L. Moffitt Cancer Center, 12902 USF Magnolia Drive, Tampa, FL 33612, USA; University of South Florida, 4202 E. Fowler Avenue, Tampa, FL 33620, USA. Electronic address:

Quantitative image features, also known as radiomic features, have shown potential for predicting treatment outcomes in several body sites. We quantitatively analyzed Fluorine-fluorodeoxyglucose (F-FDG) Positron Emission Tomography (PET) uptake heterogeneity in the Metabolic Tumor Volume (MTV) of eighty cervical cancer patients to investigate the predictive performance of radiomic features for two treatment outcomes: the development of distant metastases (DM) and loco-regional recurrent disease (LRR). We aimed to fit the highest predictive features in multiple logistic regression models (MLRs). To generate such models, we applied backward feature selection method as part of Leave-One-Out Cross Validation (LOOCV) within a training set consisting of 70% of the original patient cohort. The trained MLRs were tested on an independent set consisted of 30% of the original cohort. We evaluated the performance of the final models using the Area under the Receiver Operator Characteristic Curve (AUC). Accordingly, six models demonstrated superior predictive performance for both outcomes (four for DM and two for LRR) when compared to both univariate-radiomic feature models and Standard Uptake Value (SUV) measurements. This demonstrated approach suggests that the ability of the pre-radiochemotherapy PET radiomics to stratify patient risk for DM and LRR could potentially guide management decisions such as adjuvant systemic therapy or radiation dose escalation.
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http://dx.doi.org/10.1016/j.ejmp.2017.10.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771366PMC
February 2018

Accounting for reconstruction kernel-induced variability in CT radiomic features using noise power spectra.

J Med Imaging (Bellingham) 2018 Jan 14;5(1):011013. Epub 2017 Dec 14.

University of South Florida, Department of Physics, Tampa, Florida, United States.

Large variability in computed tomography (CT) radiomics feature values due to CT imaging parameters can have subsequent implications on the prognostic or predictive significance of these features. Here, we investigated the impact of pitch, dose, and reconstruction kernel on CT radiomic features. Moreover, we introduced correction factors to reduce feature variability introduced by reconstruction kernels. The credence cartridge radiomics and American College of Radiology (ACR) phantoms were scanned on five different scanners. ACR phantom was used for 3-D noise power spectrum (NPS) measurements to quantify correlated noise. The coefficient of variation (COV) was used as the variability assessment metric. The variability in texture features due to different kernels was reduced by applying the NPS peak frequency and region of interest (ROI) maximum intensity as correction factors. Most texture features were dose independent but were strongly kernel dependent, which is demonstrated by a significant shift in NPS peak frequency among kernels. Percentage improvement in robustness was calculated for each feature from original and corrected %COV values. Percentage improvements in robustness of 19 features were in the range of 30% to 78% after corrections. We show that NPS peak frequency and ROI maximum intensity can be used as correction factors to reduce variability in CT texture feature values due to reconstruction kernels.
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http://dx.doi.org/10.1117/1.JMI.5.1.011013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5729963PMC
January 2018

Impact of sarcopenia on outcomes of locally advanced esophageal cancer patients treated with neoadjuvant chemoradiation followed by surgery.

J Gastrointest Oncol 2017 Oct;8(5):808-815

Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.

Background: Sarcopenia is an independent predictor of clinical outcomes in multiple gastrointestinal cancers. Total psoas area (TPA), as measured on a single cross-sectional CT image at the L4 vertebral body level, has been correlated with sarcopenia. We sought to evaluate whether TPA was predictive of acute grade ≥3 toxicity, pathologic response, and overall survival in patients with locally advanced esophageal cancer receiving tri-modality therapy.

Methods: An institutional database of esophageal cancer patients treated with neoadjuvant chemoradiation followed by surgery was queried. Of 77 patients treated from 2008 to 2012 with intensity modulated radiation therapy (IMRT) and image guided radiation therapy (IGRT), 56 patients were eligible based on having CT imaging that included the L4 vertebral body. The L4 vertebra was identified on axial CT and the psoas muscle was manually contoured bilaterally to determine the skeletal muscle index. Sarcopenia was defined by the presence of the psoas area less than the median of the cohort. Acute toxicity was defined as within 3 months of radiotherapy based on Common Terminology Criteria for Adverse Events. ROC curve, logistic regression, and Kaplan Meier estimates were used when appropriate.

Results: Sarcopenia was associated with increased acute grade ≥3 toxicity from chemoradiation by ROC analysis using a cut off of 841.5 mm/m (P=0.003, AUC 0.709, sensitivity 60.9%, specificity 78.8%) and logistic regression (P=0.002). Patients with TPA <841.5 mm/m were 5.78 times more likely to develop grade 3 or higher toxicity (P=0.004). Sarcopenia did not predict a difference in overall survival (P=0.217) and was not significant for pathologic complete response or favorable pathologic response (TRG 0/1).

Conclusions: In our cohort of patients, sarcopenia was associated with a significant increase in acute grade ≥3 toxicity with chemoradiation, suggesting a potential role for neoadjuvant patient selection strategies. There was no difference in pathologic response or overall survival.
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http://dx.doi.org/10.21037/jgo.2017.06.11DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5674260PMC
October 2017

Ventilation Series Similarity: A Study for Ventilation Calculation Using Deformable Image Registration and 4DCT to Avoid Motion Artifacts.

Contrast Media Mol Imaging 2017 17;2017:9730380. Epub 2017 Sep 17.

Radiation Oncology, Moffitt Cancer Center, Tampa, FL, USA.

The major problem with ventilation distribution calculations using DIR and 4DCT is the motion artifacts in 4DCT. Quite often not all phases would exhibit mushroom motion artifacts. If the ventilation series similarity is sufficiently robust, the ventilation distribution can be calculated using only the artifact-free phases. This study investigated the ventilation similarity among the data derived from different respiration phases. Fifteen lung cancer cases were analyzed. In each case, DIR was performed between the end-expiration phase and all other phases. Ventilation distributions were then calculated using the deformation matrices. The similarity was compared between the series ventilation distributions. The correlation between the majority phases was reasonably good, with average SCC values between 0.28 and 0.70 for the original data and 0.30 and 0.75 after smoothing. The better correlation between the neighboring phases, with average SCC values between 0.55 and 0.70 for the original data, revealed the nonlinear property of the dynamic ventilation. DSC analysis showed the same trend. To reduce the errors if motion artifacts are present, the phases without serious mushroom artifacts may be used. To minimize the effect of the nonlinearity in dynamic ventilation, the calculation phase should be chosen as close to the end-inspiration as possible.
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http://dx.doi.org/10.1155/2017/9730380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5623778PMC
August 2018

CT imaging features associated with recurrence in non-small cell lung cancer patients after stereotactic body radiotherapy.

Radiat Oncol 2017 Sep 25;12(1):158. Epub 2017 Sep 25.

Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL, 33612, USA.

Background: Predicting recurrence after stereotactic body radiotherapy (SBRT) in non-small cell lung cancer (NSCLC) patients is problematic, but critical for the decision of following treatment. This study aims to investigate the association of imaging features derived from the first follow-up computed tomography (CT) on lung cancer patient outcomes following SBRT, and identify patients at high risk of recurrence.

Methods: Fifty nine biopsy-proven non-small cell lung cancer patients were qualified for this study. The first follow-up CTs were performed about 3 months after SBRT (median time: 91 days). Imaging features included 34 manually scored radiological features (semantics) describing the lesion, lung and thorax and 219 quantitative imaging features (radiomics) extracted automatically after delineation of the lesion. Cox proportional hazard models and Harrel's C-index were used to explore predictors of overall survival (OS), recurrence-free survival (RFS), and loco-regional recurrence-free survival (LR-RFS). Five-fold cross validation was performed on the final prognostic model.

Results: The median follow-up time was 42 months. The model for OS contained Eastern Cooperative Oncology Group (ECOG) performance status (HR = 3.13, 95% CI: 1.17-8.41), vascular involvement (HR = 3.21, 95% CI: 1.29-8.03), lymphadenopathy (HR = 3.59, 95% CI: 1.58-8.16) and the 1st principle component of radiomic features (HR = 1.24, 95% CI: 1.02-1.51). The model for RFS contained vascular involvement (HR = 3.06, 95% CI: 1.40-6.70), vessel attachment (HR = 3.46, 95% CI: 1.65-7.25), pleural retraction (HR = 3.24, 95% CI: 1.41-7.42), lymphadenopathy (HR = 6.41, 95% CI: 2.58-15.90) and relative enhancement (HR = 1.40, 95% CI: 1.00-1.96). The model for LR-RFS contained vascular involvement (HR = 4.96, 95% CI: 2.23-11.03), lymphadenopathy (HR = 2.64, 95% CI: 1.19-5.82), circularity (F13, HR = 1.60, 95% CI: 1.10-2.32) and 3D Laws feature (F92, HR = 1.96, 95% CI: 1.35-2.83). Five-fold cross-validated the areas under the receiver operating characteristic curves (AUC) of these three models were all above 0.8.

Conclusions: Our analysis reveals disease progression could be prognosticated as early as 3 months after SBRT using CT imaging features, and these features would be helpful in clinical decision-making.
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http://dx.doi.org/10.1186/s13014-017-0892-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5613447PMC
September 2017

Predicting Patient-Specific Radiotherapy Protocols Based on Mathematical Model Choice for Proliferation Saturation Index.

Bull Math Biol 2018 05 5;80(5):1195-1206. Epub 2017 Jul 5.

Department of Integrated Mathematical Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL, 33647, USA.

Radiation is commonly used in cancer treatment. Over 50% of all cancer patients will undergo radiotherapy (RT) as part of cancer care. Scientific advances in RT have primarily focused on the physical characteristics of treatment including beam quality and delivery. Only recently have inroads been made into utilizing tumor biology and radiobiology to design more appropriate RT protocols. Tumors are composites of proliferating and growth-arrested cells, and overall response depends on their respective proportions at irradiation. Prokopiou et al. (Radiat Oncol 10:159, 2015) developed the concept of the proliferation saturation index (PSI) to augment the clinical decision process associated with RT. This framework is based on the application of the logistic equation to pre-treatment imaging data in order to estimate a patient-specific tumor carrying capacity, which is then used to recommend a specific RT protocol. It is unclear, however, how dependent clinical recommendations are on the underlying tumor growth law. We discuss a PSI framework with a generalized logistic equation that can capture kinetics of different well-known growth laws including logistic and Gompertzian growth. Estimation of model parameters on the basis of clinical data revealed that the generalized logistic model can describe data equally well for a wide range of the generalized logistic exponent value. Clinical recommendations based on the calculated PSI, however, are strongly dependent on the specific growth law assumed. Our analysis suggests that the PSI framework may best be utilized in clinical practice when the underlying tumor growth law is known, or when sufficiently many tumor growth models suggest similar fractionation protocols.
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http://dx.doi.org/10.1007/s11538-017-0279-0DOI Listing
May 2018

Fiducial markers coupled with 3D PET/CT offer more accurate radiation treatment delivery for locally advanced esophageal cancer.

Endosc Int Open 2017 Jun 31;5(6):E496-E504. Epub 2017 May 31.

H. Lee Moffitt Cancer Center and Research Institute, Department of Radiation Oncology, Tampa, FL, USA.

Background And Aims:  The role of three-dimensional positron emission tomography/computed tomography (3 D PET/CT) in esophageal tumors that move with respiration and have potential for significant mucosal inflammation is unclear. The aim of this study was to determine the correlation between gross tumor volumes derived from 3 D PET/CT and endoscopically placed fiducial markers.

Methods:  This was a retrospective, IRB approved analysis of 40 patients with esophageal cancer with fiducials implanted and PET/CT. The centroid of each fiducial was identified on PET/CT images. Distance between tumor volume and fiducials was measured using axial slices. Image features were extracted and tested for pathologic response predictability.

Results:  The median adaptively calculated threshold value of the standardized uptake value (SUV) to define the metabolic tumor volume (MTV) border was 2.50, which corresponded to a median 23 % of the maximum SUV. The median distance between the inferior fiducial centroid and MTV was - 0.60 cm (- 3.9 to 2.7 cm). The median distance between the superior fiducial centroid and MTV was 1.25 cm (- 4.2 to 6.9 cm). There was no correlation between MTV-to-fiducial distances greater than 2 cm and the gastroenterologist who performed the fiducial implantation. Eccentricity demonstrated statistically significant correlations with pathologic response.

Conclusions:  There was a stronger correlation between inferior fiducial location and MTV border compared to the superior extent. The etiology of the discordance superiorly is unclear, potentially representing benign secondary esophagitis, presence of malignant nodes, inflammation caused by technical aspects of the fiducial placement itself, or potential submucosal disease. Given the concordance inferiorly and the ability to more precisely set up the patient with daily image guidance matching to fiducials, it may be possible to minimize the planning tumor volume (PTV) margin in select patients, thereby, limiting dose to normal structures.
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http://dx.doi.org/10.1055/s-0043-104861DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5451282PMC
June 2017

Imaging features from pretreatment CT scans are associated with clinical outcomes in nonsmall-cell lung cancer patients treated with stereotactic body radiotherapy.

Med Phys 2017 Aug 24;44(8):4341-4349. Epub 2017 Jun 24.

Department of Cancer Imaging and Metabolism, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.

Purpose: To investigate whether imaging features from pretreatment planning CT scans are associated with overall survival (OS), recurrence-free survival (RFS), and loco-regional recurrence-free survival (LR-RFS) after stereotactic body radiotherapy (SBRT) among nonsmall-cell lung cancer (NSCLC) patients.

Patients And Methods: A total of 92 patients (median age: 73 yr) with stage I or IIA NSCLC were qualified for this study. A total dose of 50 Gy in five fractions was the standard treatment. Besides clinical characteristics, 24 "semantic" image features were manually scored based on a point scale (up to 5) and 219 computer-derived "radiomic" features were extracted based on whole tumor segmentation. Statistical analysis was performed using Cox proportional hazards model and Harrell's C-index, and the robustness of final prognostic model was assessed using tenfold cross validation by dichotomizing patients according to the survival or recurrence status at 24 months.

Results: Two-year OS, RFS and LR-RFS were 69.95%, 41.3%, and 51.85%, respectively. There was an improvement of Harrell's C-index when adding imaging features to a clinical model. The model for OS contained the Eastern Cooperative Oncology Group (ECOG) performance status [Hazard Ratio (HR) = 2.78, 95% Confidence Interval (CI): 1.37-5.65], pleural retraction (HR = 0.27, 95% CI: 0.08-0.92), F2 (short axis × longest diameter, HR = 1.72, 95% CI: 1.21-2.44) and F186 (Hist-Energy-L1, HR = 1.27, 95% CI: 1.00-1.61); The prognostic model for RFS contained vessel attachment (HR = 2.13, 95% CI: 1.24-3.64) and F2 (HR = 1.69, 95% CI: 1.33-2.15); and the model for LR-RFS contained the ECOG performance status (HR = 2.01, 95% CI: 1.12-3.60) and F2 (HR = 1.67, 95% CI: 1.29-2.18).

Conclusions: Imaging features derived from planning CT demonstrate prognostic value for recurrence following SBRT treatment, and might be helpful in patient stratification.
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http://dx.doi.org/10.1002/mp.12309DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5553698PMC
August 2017

Superficial and peripheral dose in compensator-based FFF beam IMRT.

J Appl Clin Med Phys 2017 Jan 21;18(1):151-156. Epub 2016 Dec 21.

Radiation Oncology, Moffitt Cancer Center, Tampa, FL, USA.

Flattening filter-free (FFF) beams produce higher dose rates. Combined with compensator-based intensity modulated radiotherapy (IMRT) techniques, the dose delivery for each beam can be much shorter compared to the flattened beam MLC-based or flattened beam compensator-based IMRT. This 'snap shot' IMRT delivery is beneficial to patients for tumor motion management. Due to softer energy, superficial doses in FFF beam treatment are usually higher than those from flattened beams. Due to no flattening filter, thus less photon scattering, peripheral doses are usually lower in FFF beam treatment. However, in compensator-based IMRT using FFF beams, the compensator is in the beam pathway. Does it introduce beam hardening effects and scattering such that the superficial dose is lower and peripheral dose is higher compared to FFF beam MLC-based IMRT? This study applied Monte Carlo techniques to investigate the superficial and peripheral doses in compensator-based IMRT using FFF beams and compared it to the MLC-based IMRT using FFF beams and flattened beams. Besides varying thicknesses of brass slabs to simulate varying thicknesses of compensators, a simple cone-shaped compensator was simulated to mimic a clinical application. The dose distribution in water phantom by the cone-shaped compensator was then simulated by multiple MLC-defined FFF and flattened beams with varying apertures. After normalization to the maximum dose, D, the superficial and peripheral doses were compared between the FFF beam compensator-based IMRT and FFF/flattened beam MLC-based IMRT. The superficial dose at the central 0.5 mm depth was about 1% (of D) lower in the compensator-based 6 MV FFF (6FFF) IMRT compared to the MLC-based 6FFF IMRT, and about 8% higher than the flattened 6 MV MLC-based IMRT dose. At 8 cm off-axis at depth of central maximum dose, d, the peripheral dose between the 6FFF and flattened 6 MV MLC demonstrated similar doses, while the compensator dose was about 1% (of D) higher. Compensators reduce the superficial doses slightly compared to open FFF beams, but increases the peripheral doses due to scatter in the compensator.
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http://dx.doi.org/10.1002/acm2.12018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5689887PMC
January 2017

Rectal dose to prostate cancer patients treated with proton therapy with or without rectal spacer.

J Appl Clin Med Phys 2017 Jan 21;18(1):32-39. Epub 2016 Nov 21.

Department of Radiation Oncology, University of Maryland, Baltimore School of Medicine, Baltimore, MD, USA.

The purpose of this study was to evaluate whether a spacer inserted in the prerectal space could reduce modeled rectal dose and toxicity rates for patients with prostate cancer treated in silico with pencil beam scanning (PBS) proton therapy. A total of 20 patients were included in this study who received photon therapy (12 with rectal spacer (DuraSeal™ gel) and 8 without). Two PBS treatment plans were retrospectively created for each patient using the following beam arrangements: (1) lateral-opposed (LAT) fields and (2) left and right anterior oblique (LAO/RAO) fields. Dose volume histograms (DVH) were generated for the prostate, rectum, bladder, and right and left femoral heads. The normal tissue complication probability (NTCP) for ≥grade 2 rectal toxicity was calculated using the Lyman-Kutcher-Burman model and compared between patients with and without the rectal spacer. A significantly lower mean rectal DVH was achieved in patients with rectal spacer compared to those without. For LAT plans, the mean rectal V70 with and without rectal spacer was 4.19 and 13.5%, respectively. For LAO/RAO plans, the mean rectal V70 with and without rectal spacer was 5.07 and 13.5%, respectively. No significant differences were found in any rectal dosimetric parameters between the LAT and the LAO/RAO plans generated with the rectal spacers. We found that ≥ 9 mm space resulted in a significant decrease in NTCP modeled for ≥grade 2 rectal toxicity. Rectal spacers can significantly decrease modeled rectal dose and predicted ≥grade 2 rectal toxicity in prostate cancer patients treated in silico with PBS. A minimum of 9 mm separation between the prostate and anterior rectal wall yields the largest benefit.
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http://dx.doi.org/10.1002/acm2.12001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5689902PMC
January 2017
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