核医学与放射治疗

Objectives: To determine the safety and performance of miniature neuromuscular stimulator called MicroStimulator (MS) during radiation therapy (RT) of head and neck cancer (HNC).
Study Design: Pilot study
Methods: Four patients who underwent modified radical neck dissection for HNC received MS implants. The implant was placed 2-3 mm above and parallel to the hypoglossal nerve. All patients had tracheotomy and gastric tubes placed during surgery. Stimulation thresholds were obtained in three patients and electrical exercise programs were initiated in two patients. One patient completed the study, started RT and stimulation of the MS 3-4 weeks after surgery. The implant was energized and controlled by a radio frequency magnetic field from an external coil placed near the implant. Patients underwent stimulation of the MS one hour per day using intermittent trains of stimuli generating fused, maximal contractions.
Results: No postoperative or implant specific complication was noted. All patients required and tolerated stimulation without pain or discomfort. Visible contraction of muscles of swallowing was noted in both patients during stimulation indicating that MS remained functional during RT. All patients used the device at home and maintained their oral feeding and weight. None had aspiration pneumonia.
Conclusions: MS appears to be a safe device for stimulation of swallowing muscles during MS for HNC. Implant performance is not affected by RT. It effectively stimulates the nerves to induce robust contraction of muscles of swallowing and laryngeal elevation. High patient compliance was achieved with this implant.

Abstract
Purpose: To predict overall survival (OS) in non-metastatic esophageal cancer using texture analysis of pre-therapy computed tomography (CT) images.
Materials and Methods: Records from 762 non-metastatic esophageal cancer patients with non-contrast CT scans (obtained from 1998-2011) before receiving chemoradiation were retrospectively reviewed. 328 quantitative image features were extracted from the esophageal gross tumor volume (GTV). A random survival forest model compared how well five of these features (entropy, histogram 10th percentile, volume, volume-to-area ratio, fraction GTV pruned after thresholding) predicted OS versus all 328 features. Cox proportional hazards modeling was used to derive scores, based on these five features, which could stratify patients by survival in a training set consisting of 50% of the 762 cases, chosen randomly from the data. This model was then tested in a validation set (remaining 50% of cases). Multivariate analysis was done with the image-derived score and other prognostic variables. Results: CT texture analysis based on the five image-derived features yielded a similar concordance rate for predicting OS (56%) as did all 328 features (56%), and in fact showed higher concordance for predicting OS than disease stage alone (44%). This image-derived score was also able to significantly stratify OS (P<0.05) in both the training and validation set, as well as independently predict OS in multivariate analysis (HR 1.61, 95% CI 1.13-2.29, P=0.009), along with stage, treatment with surgery, tumor grade, and radiation modality.
Conclusions: Texture features from pretreatment CT images can independently predict OS in patients with non-metastatic esophageal carcinoma.

Abstract
Recent advances in the application of nanotechnology in medicine, often referred to as nanomedicine, may revolutionize our approach to healthcare. Cancer nanotechnology is a relatively novel interdisciplinary area of comprehensive research that combines the basic sciences, like biology and chemistry, with engineering and medicine. Nanotechnology involves creating and utilizing the constructs of variable chemistry and architecture with dimensions at the nanoscale level comparable to those of biomolecules or biological vesicles in the human body. Operating with submolecular interactions, it offers the potential for unique and novel approaches with a broad spectrum of applications in cancer treatment including areas such as diagnostics, therapeutics, and prognostics. Nanotechnology also opens pathways to developing new and efficient therapeutic approaches to cancer treatment that can overcome numerous barriers posed by the human body compared to conventional approaches. Improvement in chemotherapeutic delivery through enhanced solubility and prolonged retention time has been the focus of research in nanomedicine. The submicroscopic size and flexibility of nanoparticles offer the promise of selective tumor access. Formulated from a variety of substances, nanoparticles are configured to transport myriad substances in a controlled and targeted fashion to malignant cells while minimizing the damage to normal cells. They are designed and developed to take advantage of the morphology and characteristics of a malignant tumor, such as leaky tumor vasculature, specific cell surface antigen expression, and rapid proliferation. Nanotechnology offers a revolutionary role in both diagnostics (imaging, immune-detection) and treatment (radiation therapy, chemotherapy, immunotherapy, thermotherapy, photodynamic therapy, and anti-angiogenesis). Moreover, nanoparticles may be designed to offer a multifunctional approach operating simultaneously as an effective and efficient anticancer drug as well as an imaging material to evaluate the efficacy of the drug for treatment follow-up. In recent years, nanomedicine has exhibited strong promise and progress in radically changing the approach to cancer detection and treatment.

Abstract
Thyroid carcinoma is the commonest endocrine malignancy, although less than 1% of all cancers. Osseous metastases are more often associated with the follicular type of thyroid carcinoma. Fewer than 5% of patients present with distant metastases. We present a case of sternal metastasis being the first observed feature of follicular thyroid carcinoma. A 62-year old female developed a painless nodule over her sternum, which progressively enlarged over approximately two years. Patient was seen at another medical facility, where histology of the mass revealed metastatic follicular thyroid carcinoma. Subsequent left thyroid lobectomy confirmed follicular thyroid cancer on histology. She was treated with 100 mCi of radioiodine I-131 (RAI), and suppressive L-thyroxine therapy implemented thereafter. However, the sternal mass recurred seven months post-sternectomy. She patient was then referred to our facility. The mass was deemed inoperable. Thus, she was treated with 200 mCi of RAI under steroid cover. The RAI therapy scan showed intense uptake in the sternal mass as well as less prominent thyroid bed uptake. The patient has since been referred for external beam radiation therapy. The clinician is reminded of one of the modes of presentation of thyroid cancer. Thyroid cancer has been deemed an indolent tumour but may also exhibit aggressive behaviour as occurred in this patient. This case also buttresses the importance of early biopsy and diagnosis in the investigation of tumours.

Abstract
Introduction: Prostate cancer (PCa) second leading cause of cancer-related deaths among men worldwide. There are publications in the literature examining the relation between obesity and PCa, but there is not publication about the relation between obesity and bone metastases in PCa. The aim of this study is to determine whether there is a relation between bone metastasis, PSA, Gleason score, BMI and visceral fat percentage (VFP) in PCa patients.
Methods: Thirty-four patients with PCa who performed bone scintigraphy included to study. Mean age was 71.3 ± 6.9 years. All patients' height, weight, VFP and BMI were calculated. PSA levels, Gleason scores, VFP and BMI of patients with and without bone metastases were compared.
Results: On the bone scintigraphy 14 patients had bone metastasis and there was no metastases in 20 patients. PSA levels and Gleason scores were higher in patients with bone metastases than in patients without bone metastases and this was statistically significant (p= 0.004). While the BMI level was 26.15 kg/m2 (22.7-33.5) in patients with bone metastasis, it was 26.5 kg/m2 (20.7-43.9) in patients without bone metastasis. VFP was 11 (6-27) in patients with bone metastasis and 9 (3-17) in patients without bone metastasis. Although the VFP was higher in patients with bone metastases; this was not statistically significant (p=0.15).
Conclusion: Our data suggest that there is a significant correlation between bone metastasis and high Gleason score and PSA level, but there is not significant correlation between bone metastasis and BMI, VFP in PCa.

Abstract
Purpose/Objectives: Heterogeneity index (HI) has been described in the literature as a tool for evaluating dose gradients within a planning target volume (PTV). HI may be expressed as D1/D95 where D1 and D95 equal the dose encompassing 1% and 95% of the target volume. The purpose of this study is to evaluate the effect of target volume dose heterogeneity on dose received by local organs at risk in the treatment of low and intermediate risk prostate cancer.
Materials/Methods: Treatment plans were reviewed for 157 patients with low or intermediate risk prostate cancer treated with dose-escalated radiation therapy between 6/2007 and 2/2012. Patients treated in the post-operative setting or receiving pelvic nodal irradiation were excluded. Patients were treated with either standard intensity modulation (IMRT) using 7 or 8 fields or 2-arc volumetric modulated arc therapy (VMAT). All patients had daily image-guidance. PTV HI (D1/D95) and dose-volume histogram (DVH) data at 8 dose levels for rectum and bladder were recorded. Patients were categorized into two groups (low HI or high HI) with respect to median index score. A two-tailed t-test was used to test for differences in dose received by rectum and bladder for the two groups.

Results: For the 157 plans evaluated, mean PTV volume was 164cc and mean prescription dose was 7833cGy. Median HI was 1.04 (range 1.0-1.08). Low HI (≤1.04) was found to correlate with significantly lower rectal V50 (p=0.02), V55 (p=0.01), V60 (p=0.01), V65 (p=0.01), and V70 (p=0.01). There was no significant correlation with dose received by bladder at any dose level. HI was similar for patients treated with standard IMRT and VMAT (p=0.85).
Conclusions: Target volume HI ≤1.04 is associated with more favorable rectal doses at clinically relevant dose-levels. We believe HI may serve as a valuable metric in prostate cancer treatment planning. Further work is needed to correlate these dosimetric findings with clinical outcomes.

Abstract
Aims: We evaluated the response and toxicity, after long-term follow up of Iodine-131 rituximab radioimmunotherapy in patients with follicular lymphoma under the routine clinical care of a single hematologist over a period of 12 years.

Materials and methods: Patients received 131I-rituximab radioimmunotherapy according to a standard, personalized dosimetry protocol predicated upon a prescribed whole body radiation absorbed dose of 0.75Gy. Four doses of maintenance rituximab were subsequently administered over 12 months.
 

Results: Response rate was 97% with 24(77%) patients experiencing a complete remission confirmed on 18F-fluorodeoxyglucose positron emission tomography-computerized tomography scan. The cohort of 3 patients with duodenal lymphoma all achieved complete remission lasting 4-5 years.
Disclosure statement: There is no conflict of interest to declare with the publication of this work. No author has a financial incentive associated with the publication of this article.

Conclusion: 131I-rituximab radioimmunotherapy is an effective, safe, affordable, repeatable treatment which does not compromise future therapy options upon relapse. It is practical, being administered on an outpatient basis, and referring physicians maintain governance of their patients.

Abstract

Background: We investigated the relationship of standardized uptake values (SUVs) to radiobiological parameters, such a 25 s tumor control probability (TCP), to allow for quantitative prediction of tumor response based on SUVs from 18F fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) before and after treatment for esophageal cancer.
Methods: We analyzed data from 20 esophageal cancer patients treated with chemoradiotherapy (CRT) followed by surgery. Tumor pathologic response to CRT was assessed in surgical specimens. Patients underwent 18F-FDG PET imaging before and after CRT. Rigid image registration was performed between both images. Because TCP in a heterogeneous tumor is a function of average cell survival, we modeled TCP as a function of , a possible surrogate for average cell survival (=). TCP was represented by a sigmoid function with two parameters: SUVR50, the at which TCP=0.5, and γ50, the slope of the curve at SUVR50. The two parameters and their confidence intervals (CIs) were estimated using the maximum-likelihood method. The correlation between SUV before CRT and SUV change was also studied.
Results: A TCP model as a function of SUV before and after treatment was developed for esophageal cancer patients. The maximum-likelihood estimate of SUVR50 was 0.47 (90% CI, 0.30-0.61) and for γ50was 1.62 (90% CI, 0-4.2). High initial SUV and larger metabolic response (larger ) were correlated, and this correlation was stronger among responders. Conclusions: Our TCP model indicates that is a possible surrogate for cell survival in esophageal cancer patients. Although CIs are large as a result of the small patient sample, parameters for a TCP curve can be derived and an individualized TCP can be calculated for future patients. Initial SUV does not predict response, whereas a correlation is found between surrogates for initial tumor burden and cell kill during therapy.

Abstract
Aim: To dosimetrically compare and evaluate Intensity Modulated Radiation Therapy (IMRT) versus conventional five field radiotherapy (5FCRT) in postmastectomy radiotherapy (PMRT).

Material and Methods: This study included 25 consecutive patients for PMRT. Target volumes (chest wall, axilla, supraclavicular regions [SCF]) and normal structures (lungs, heart, spinal cord, opposite breast) were delineated on the planning CT scans. For each patient, one IMRT and one 5FCRT plan were generated for 50 Gy and corresponding dose volume histograms were compared. Differences in means of each set of variables were tested for significance.
 

Results: CTV and PTV of chest wall, IMC, axilla level l, ll, lll and SCF were evaluated by variables D98%,D2%, D50% V<95, V>105, V>107, homogeneity index (HI). Coverage of the PTV given chest wall was significantly better with IMRT than conventional. The HI was more with conventional 0.6+0.2, IMRT 0.1+0.1, p<0.001. PTV of axilla and SCF, D98% were better with IMRT than conventional. In IMRT HI was 0.1+0.1 while 0.4+0.2 conventional p<0.02. In lung V20 of the ipsilateral lung with IMRT was significantly lower than that of the conventional. In heart D33% by IMRT was 17.3 + 10.0 Gy and 33.2+11.3Gy in conventional (p<0.001). Mean dose received by opposite breast was 5.8 + 1.8 Gy by IMRT and 2.0+1.0Gy by conventional p<0.001.
Conclusion: IMRT technique is superior to the conventional technique due to its better chest wall, axilla and SCF coverage. IMRT significantly reduced heart, lung and spinal cord doses as compared with conventional technique.

Abstract
Introduction: This Centre has previously reported outcomes for patients treated with neoadjuvant hormone therapy (NAHT) and 52.5Gy in 20 fractions. We now present the outcome data for patients treated with 55Gy in 20 fractions and NAHT.

Methods and Materials: 584 patients were treated for T1-T3 node negative prostate cancer. The median age was 67.2 years (range 49-80). All patients received 3 months of NAHT followed by CT planned conformal radiotherapy to the prostate using 55Gy in 20 fractions. 147 patients considered at particularly high risk of relapse also received 2 years of adjuvant androgen deprivation. Outcomes were obtained through serial PSA measurement. Patients were classified into prognostic groups according to Zelefsky criteria. PSA relapse was defined according to Houston criteria. The outcomes with 55Gy were compared with the 52.5Gy cohort.
Results: The 10 year cause specific survival increased from 67.3% with 52.5Gy to 92.9% in the 55Gy group. Patients receiving 55Gy had better outcomes than those receiving 52.5Gy in all prognostic groups with or without adjuvant hormone use. PSA relapse free survival at five years in the patients who did not receive adjuvant hormones are:- 80.2 v 63.6% in the ‘Good’, 69.5 v 43.7% in the ‘Intermediate’ and 40.3 v 15.3% in the ‘Poor’ prognostic groups (p<0.01).

Conclusions: Our results demonstrate improved outcomes with prostate radiotherapy across all prognostic groups with a modest dose escalation from 52.5 to 55Gy in 20 fractions. This supports evidence of a steep dose response gradient and a low alpha beta ratio in this cancer.