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Radiotherapy is the treatment of cancer and other diseases with high energy (ionising) radiation. Ionising radiation damages or destroys cells in the area being treated making it impossible for the cancer cells to continue to grow and multiply. Most radiotherapy is delivered from the outside of the body (external beam radiotherapy) usually in the form of high energy X-rays or sometimes as Gamma rays. For certain cancers a radioactive implant can be placed next to the tumour inside the body (internal radiotherapy). As radiotherapy can damage normal cells as well as cancer cells there can be potential side effects, these may depend on the radiotherapy dose, site(s) of treatment, age and other factors.

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Overviews - What is Radiotherapy?
Recent Research
Radiation Oncology (medical specialty)
Specialist Journals

Overviews - What is Radiotherapy? (8 links)

Recent Research

Chen MY, Wang YC, Wu TH, et al.
Efficacy of External Beam Radiation-Based Treatment plus Locoregional Therapy for Hepatocellular Carcinoma Associated with Portal Vein Tumor Thrombosis.
Biomed Res Int. 2016; 2016:6017406 [PubMed] Free Access to Full Article Related Publications
Background. Portal vein tumor thrombosis (PVTT) is a common event in advanced hepatocellular carcinoma (HCC). The optimal treatment for these patients remains controversial. Methods. A retrospective review of 149 patients who had unresectable HCC associated with PVTT between January 2005 and December 2012 was performed. Outcomes related to external beam radiation-based treatment were measured, and clinicopathological features and parameters affecting prognosis were analyzed as well. Results. The radiotherapeutic response of PVTT was an important element that affected the overall treatment response of HCC. Serum α-fetoprotein < 400 ng/mL, the presence of a radiotherapeutic response on PVTT, and receiving additional locoregional therapy were significant prognostic factors affecting the survival of patients. Patients who had received additional locoregional therapy obtained a better outcome, and six of them were eventually able to undergo surgical management with curative intent. Conclusion. The outcome of HCC associated with PVTT remains pessimistic. In addition to the current recommended treatment using sorafenib, a combination of external beam radiotherapy targeting PVTT and locoregional therapy for intrahepatic HCC might be a promising strategy for patients who had unresectable HCC with PVTT. This approach could perhaps offer patients a favorable outcome as well as a possible cure with following surgical management.

Tanaka O, Komeda H, Iida T, et al.
Fiducial marker for prostate radiotherapy: comparison of 0.35- and 0.5-mm-diameter computed tomography and magnetic resonance images.
Radiol Med. 2017; 122(3):204-207 [PubMed] Related Publications
PURPOSE: When performing intensity-modulated radiotherapy for prostate cancer, a marker is inserted into the prostate to enable the recognition of its position using cone-beam computed tomography (CT). However, it is difficult to recognize the prostatic outline using CT alone. Magnetic resonance imaging (MRI) can depict the prostatic outline better than CT. In treatment plans using CT and MRI registration, various markers are used in institutions; however, the selection of an optimal marker size is difficult. Comparison of a different fiducial marker study was conducted using phantom, but no study in vivo was found. Therefore, we prospectively investigated the effects of different marker diameter sizes using CT and MR images.
METHODS: Thirty-one consecutive patients were enrolled in this study. CT and MRI were performed 3 weeks after marker placement. The 0.35-mm-diameter marker was placed on the left side of the prostate, and the 0.5-mm-diameter marker was placed on the right side. The length of each marker was 10 mm. The better MRI image was selected between those obtained using T2*-two-dimensional weighted image (T2*2D) and T2*-three-dimensional weighted image (T2*3D). Two observers evaluated and scored the prostatic outline image quality as well as visualized the prostatic markers using CT and MRI.
RESULTS: MRI was significantly superior to CT in depicting the prostatic outline. The CT artifacts were significantly lesser for the 0.35-mm-diameter marker than for the 0.5-mm-diameter marker. The degree of marker recognition using MRI was significantly better with the 0.5-mm-diameter marker.
CONCLUSION: The 0.5-mm-diameter fiducial marker had significantly better visualization than the 0.35-mm-diameter marker. While CT artifacts were significantly worse with the 0.5-mm-diameter marker, the artifact level was tolerable for clinical practice. Therefore, we recommend the 0.5-mm-diameter diameter marker in terms of prostatic outline and marker visualization using MRI.

Snider 3rd JW, Mutaf Y, Nichols E, et al.
Dosimetric Improvements with a Novel Breast Stereotactic Radiotherapy Device for Delivery of Preoperative Partial-Breast Irradiation.
Oncology. 2017; 92(1):21-30 [PubMed] Related Publications
OBJECTIVE: Partial-breast irradiation (PBI) with external-beam radiotherapy has produced higher than expected rates of fair-to-poor cosmesis. Worsened outcomes have been correlated with larger volumes of breast tissue exposed to radiation. A novel breast-specific stereotactic radiotherapy (BSRT) device (BSRTD) has been developed at our institution and has shown promise in delivering highly conformal dose distributions. We compared normal tissue sparing with this device with that achieved with intensity-modulated radiation therapy (IMRT)-PBI.
METHODS: Fifteen women previously treated with breast conservation therapy were enrolled on an institutional review board-approved protocol. Each of them underwent CT simulation in the prone position using the BSRTD-specific immobilization system. Simulated postoperative and preoperative treatment volumes were generated based on surgical bed/clip position. Blinded planners generated IMRT-PBI plans and BSRT plans for each set of volumes. These plans were compared based on clinically validated markers for cosmetic outcome and toxicity using a Wilcoxon rank-sum test.
RESULTS: The BSRT plans consistently reduced the volumes receiving each of several dose levels (Vx) to breast tissue, the chest wall, the lung, the heart, and the skin in both preoperative and postoperative settings (p < 0.05). Preoperative BSRT yielded particularly dramatic improvements.
CONCLUSION: The novel BSRTD has demonstrated significant dosimetric benefits over IMRT-PBI. Further investigation is currently proceeding through initial clinical trials.

Nose T, Otani Y, Asahi S, et al.
A Japanese prospective multi-institutional feasibility study on accelerated partial breast irradiation using interstitial brachytherapy: clinical results with a median follow-up of 26 months.
Breast Cancer. 2016; 23(6):861-868 [PubMed] Related Publications
BACKGROUND: A Japanese prospective multi-institutional feasibility study on accelerated partial breast irradiation using interstitial brachytherapy was performed. The first clinical results were reported with a median follow-up of 26 months.
PATIENTS AND METHODS: Forty-six female breast cancer patients with positive hormone receptors and tumors ≤3 cm, pN0M0, completed the protocol treatment. After breast-conserving surgery and histological confirmation of negative surgical margins and pN0, brachytherapy applicators were implanted either postoperatively (n = 45) or intraoperatively (n = 1). High-dose-rate brachytherapy of 36 Gy/6 fractions was delivered. All clinical data were prospectively collected using case report forms and the Common Terminology Criteria for Adverse Events ver.3.0.
RESULTS: At the median follow-up of 26 months, no breast cancer recurrence of any type was observed. Sequelae ≥G2 were dermatitis (G2, 7 %), fibrosis (G2, 11 %; G3, 4 %), fracture (G2, 2 %), pain (G2, 7 %; G3, 2 %), and soft tissue necrosis (G2, 6 %). Cosmetic outcomes evaluated by excellent/good scores were 100 % at pre-therapy (n = 46), 94 % at 12 months (n = 46), and 81 % at 24 months (n = 36), respectively.
CONCLUSIONS: Disease control and sequelae were satisfactory due to the strict eligibility and protocol-defined treatment parameters. The cosmetic outcomes were comparable to those of previous Japanese breast-conserving therapy series.

Chang L, Li L, Li W, et al.
Research on radiotherapy at different times of the day for inoperable cervical cancer.
Int J Clin Pharmacol Ther. 2016; 54(11):856-864 [PubMed] Related Publications
PURPOSE: To investigate the radiation effects and acute damage in inoperable cervical cancer patients irradiated at different times as well as the underlying mechanisms.
METHODS: 67 patients were randomized to a morning group (MG, 9:00 - 11:00 AM) and an evening group (EG, 9:00 - 11:00 PM) and both received external beam radiotherapy (RT) (50 Gy in 25 fractions) at different times. Brachytherapy (36 - 42 Gy in 6 - 7 fractions) was also performed to enhance the radiation response twice every week in all patients at the same time. Clinical therapeutic effects and acute toxicities were evaluated after RT. Flow cytometry was analyzed before and after RT.
RESULTS: Patients' response to radiation was similar in the two groups. Incidences of overall and high-grade (III - IV) diarrhea in the MG vs. the EG were 75.0% vs. 57.6% and 12.5% vs. 6.1%, respectively. The incidence of severe hematological toxicity in the EG was significantly increased compared to the MG group. Cell apoptosis in the EG was significantly higher at 9:00 - 11:00 PM than that at 9:00 - 11:00 AM after RT. No significant differences were found in Gap Phase 0/Gap Phase 1 (G0/G1), Gap Phase 2/Metaphase Phase (G2/M), and Synthesis Phase (S) phase between different times and groups, nor were expressions of Per1, Per2, and Clock. But expressions of Per1, Per2, and Clock were significantly negative with G2/M phase and positively correlated with cell apoptosis.
CONCLUSION: RT at different time intervals results in similar efficacy. However, RT in the morning reduces severe hematological toxicity. Radiation responses may be associated with circadian genes by influence of cell cycles and apoptosis.

Dunkerley N, Bartlett FR, Kirby AM, et al.
Mean heart dose variation over a course of breath-holding breast cancer radiotherapy.
Br J Radiol. 2016; 89(1067):20160536 [PubMed] Free Access to Full Article Related Publications
OBJECTIVE: The purpose of the work was to estimate the dose received by the heart throughout a course of breath-holding breast radiotherapy.
METHODS: 113 cone-beam CT (CBCT) scans were acquired for 20 patients treated within the HeartSpare 1A study, in which both an active breathing control (ABC) device and a voluntary breath-hold (VBH) method were used. Predicted mean heart doses were obtained from treatment plans. CBCT scans were imported into a treatment planning system, heart outlines defined, images registered to the CT planning scan and mean heart dose recorded. Two observers outlined two cases three times each to assess interobserver and intraobserver variation.
RESULTS: There were no statistically significant differences between ABC and VBH heart dose data from CT planning scans, or in the CBCT-based estimates of heart dose, and no effect from the order of the breath-hold method. Variation in mean heart dose per fraction over the three imaged fractions was <6 cGy without setup correction, decreasing to 3.3 cGy with setup correction. If scaled to 15 fractions, all differences between predicted and estimated mean heart doses were <0.5 Gy and in 80% of cases, they were <0.25 Gy.
CONCLUSION: Variation in mean heart dose was at an acceptable level over the duration of breath-holding radiotherapy and was well predicted by the planning system. Advances in knowledge: Mean heart dose was not adversely affected by fraction-to-fraction variations throughout a course of heart-sparing radiotherapy using two well-established breath-holding methods.

Matsuura T, Nishimura Y, Nakamatsu K, et al.
Clinical outcomes of IMRT planned with or without PET/CT simulation for patients with pharyngeal cancers.
Int J Clin Oncol. 2017; 22(1):52-58 [PubMed] Related Publications
BACKGROUND: Clinical results of computed tomography (CT) simulations and [(18)F]-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET)/CT simulations were compared retrospectively.
MATERIALS AND METHODS: Between 2006 and 2011, [(18)F]-FDG PET/CT simulation was performed on 68 consecutive patients with pharyngeal cancers (PET/CT group). As an historical control, conventional CT simulation was performed on 56 consecutive patients with pharyngeal cancer between 2000 and 2006 (CT group). In the PET/CT group, the primary sites were nasopharynx (NPC), oropharynx (OPC), and hypopharynx (HPC) in 35, 20, and 13 patients, respectively; in the CT group, the primary sites were NPC, OPC, and HPC in 21, 17, and 18 patients, respectively. All but five patients in the PET/CT group were treated with intensity modulated radiation therapy (IMRT).
RESULTS: In the PET/CT group, TNM and clinical stages changed in 11 (16 %) and eight (12 %) patients, respectively. Although the 5-year overall survival (OS) rates for the PET/CT and the CT groups were 80 and 64 %, respectively (p = 0.0420), this result may be attributable to the background difference between the two groups. Similarly, the 5-year locoregional control rates of the two groups were 82 and 70 %, respectively (p = 0.0501). Notably, marginal recurrences around the planning target volume (PTV) were only noted in four CT group patients.
CONCLUSION: PET/CT simulation was useful for delineating an accurate clinical target volume (CTV) of pharyngeal cancer, and its clinical results were satisfactory.

Gebre-Medhin M, Haghanegi M, Robért L, et al.
Dose-volume analysis of radiation-induced trismus in head and neck cancer patients.
Acta Oncol. 2016; 55(11):1313-1317 [PubMed] Related Publications
INTRODUCTION: Trismus is a treatment-related late side effect in patients treated for cancer in the head and neck region (HNC). The condition can have a considerable negative impact on nutrition, dental hygiene, ability to speak and quality of life. We have previously studied trismus within the frame of a randomized phase 3 study of HNC patients treated with mainly three-dimensional (3D) conformal radiotherapy (CRT) and found a strong association to mean radiation dose to the mastication muscles, especially the ipsilateral masseter muscle (iMAS). In the present study we have investigated trismus prevalence and risk factors in a more recent cohort of patients, treated with todays' more updated radiation techniques.
MATERIAL AND METHODS: Maximal interincisal distance (MID) was measured on 139 consecutive patients. Trismus was defined as MID ≤35 mm. Patient-, disease- and treatment-specific data were retrospectively recorded. Differences between groups were analyzed and mean absorbed dose to mastication structures was evaluated. Dosimetric comparisons were made between this study and our previous results.
RESULTS: The prevalence of trismus was 24% at a median of 16 months after completion of radiotherapy. In bivariate analysis treatment technique (3DCRT vs. intensity modulated radiotherapy or helical tomotherapy), tumor site (oropharynx vs. other sites) and mean radiation doses to the ipsilateral lateral pterygoid muscle, the paired masseter muscles and the iMAS were significantly associated with MID ≤35 mm. In multivariable analysis only mean radiation dose to the iMAS was significantly associated to MID ≤35 mm.
CONCLUSION: Mean radiation dose to the ipsilateral masseter muscle is an important risk factor for trismus development. Dose reduction to this structure during radiotherapy should have a potential to diminish the prevalence of trismus in this patient group.

Thakral P, Singla S, Vashist A, et al.
Preliminary Experience with Yttrium-90-labelled Rituximab (Chimeric Anti CD-20 Antibody) in Patients with Relapsed and Refractory B Cell Non-Hodgkins Lymphoma.
Curr Radiopharm. 2016; 9(2):160-8 [PubMed] Related Publications
BACKGROUND AND OBJECTIVES: The aim of the study is to evaluate the therapeutic efficacy and safety of Yttrium- 90 radiolabelled chimeric anti CD20 antibody-Rituximab in the treatment of patients with relapsed/ refractory B cell Non-Hodgkins Lymphoma (NHL).
METHODS: Twenty patients with relapsed/refractory CD20+ NHL in progressive state were included in the study. These patients had undergone a median of 2 (range 2-5) prior standard chemotherapy ± immunotherapy regimens. All the patients received rituximab 250 mg/m2 on days 1 and 8, and either 14 MBq/kg (0.4 mCi/kg) or 11 MBq/kg (0.3 mCi/kg) of Y-90 Rituximab on day 8 (maximum dose, 32 mCi) depending upon their platelet count. The patients were observed for systemic toxicity and response for at least 12 weeks after therapy.
RESULTS: No acute adverse effects were observed after the administration of 90Y-Rituximab. Overall response rate (ORR) was 45% of which complete response (CR) was observed in 2 patients, stable disease in 1 patient and partial response in 6 patients. The therapy was well tolerated with grade IV thrombocytopenia, neutropenia and anemia observed in 3, 4 and 2 patients respectively.
CONCLUSION: 90Y-Rituximab therapy is safe and well tolerated in high risk extensively pretreated NHL patients. Toxicity is primarily hematologic, transient and reversible.

Timon G, Ciardo D, Bazani A, et al.
Rationale and protocol of AIRC IG-13218, short-term radiotherapy for early prostate cancer with concomitant boost to the dominant lesion.
Tumori. 2016; 102(5):536-540 [PubMed] Related Publications
INTRODUCTION: Of the different treatments for early prostate cancer, hypofractionated external-beam radiotherapy is one of the most interesting and studied options.
METHODS: The main objective of this phase II clinical study is to evaluate the feasibility, in terms of the incidence of acute side effects, of a new ultra-hypofractionated scheme for low- or intermediate-risk prostate cancer patients treated with the latest imaging and radiotherapy technology, allowing dose escalation to the dominant intraprostatic lesion identified by multiparametric magnetic resonance imaging. Secondary endpoints of the study are the evaluation of the long-term tolerability of the treatment in terms of late side effects, quality of life, and efficacy (oncological outcome).
RESULTS: The study is ongoing, and we expect to complete recruitment by the end of 2016.
CONCLUSIONS: Like in previous studies, we expect ultra-hypofractionated radiation treatment for prostate cancer to be well tolerated and effective.
TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01913717.

Seiler S, Rahimi A, Choudhery S, et al.
Ultrasound-Guided Placement of Gold Fiducial Markers for Stereotactic Partial-Breast Irradiation.
AJR Am J Roentgenol. 2016; 207(3):685-8 [PubMed] Related Publications
OBJECTIVE: A novel technique of placing gold fiducial markers in the breast using ultrasound guidance was developed and performed in 51 of 55 consecutive postlumpectomy patients enrolled in a phase I dose escalation trial of accelerated partial-breast irradiation (APBI) using robotic-based stereotactic body radiation therapy (SBRT).
CONCLUSION: All 51 postoperative patients underwent successful fiducial placement without complications. Our technique of placing gold fiducial markers in proximity to the seroma cavity is considered safe and effective for breast cancer patients being treated with APBI using robotic-based SBRT.

Sumita K, Harada H, Asakura H, et al.
Re-irradiation for locoregionally recurrent tumors of the thorax: a single-institution, retrospective study.
Radiat Oncol. 2016; 11:104 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Re-irradiation (re-RT) of the thorax is challenging due to the impact of prior therapies on normal tissues, and there are few reports of definitive re-RT. The treatment toxicities and efficacy of re-RT are not well known. The aim of the present study was to assess the safety and efficacy of definitive re-RT of the thorax.
METHODS: Patients who were treated with thoracic re-RT between March 2007 and December 2014 were retrospectively analyzed. Primary and re-irradiation plans were required to have an overlap of dose distributions for the 80 % isodose level. All doses were recalculated to an equivalent dose of 2 Gy per fraction (EQD2). When possible, analysis of dose accumulation was carried out using the medical image merge (MIM) (®) software program (version 6.5, MIM Software Inc., Cleveland, OH). Administration dosages for organs at risk were defined.
RESULTS: Fourteen (67 %) and seven (33 %) patients with non-small cell carcinoma (NSCLC) and small cell carcinoma (SCLC), respectively, were identified. The patients' median age was 72 (range 53-85) years. Fifteen patients (71 %) had "proximal" tumors, defined as tumors at the distal 2 cm of the trachea, carina, and main bronchi. The median interval from initial RT to re-RT was 26.8 (range 11.4-92.3) months. Re-RT was delivered by X-ray beam and proton beam therapy in 20 (95 %) patients and 1 (5 %) patient, respectively. The median radiation dose of re-RT was 60 (range 54-87.5) Gy10 and 50 (range 50.0-87.5) Gy10 for patients with NSCLC and SCLC, respectively. Grade 3 acute radiation pneumonitis occurred in only one patient. There were no other serious complications. The median follow-up time was 22.1 (range 2.3-56.4) months. The median local progression-free survival time (LPFS) and overall survival time (OS) were 12.9 (95 % confidence interval (CI): 8.9-27.9) months and 31.4 (95 % CI: 16.9-45.9) months, respectively. Patients receiving ≥ 60 Gy10 at re-RT had longer LPFS (p = 0.04).
CONCLUSIONS: Good safety with longer OS than in previous reports was demonstrated. Re-RT seems to be a promising treatment option. Further study to define the risk-benefit ratios is necessary.

Cordoba A, Escande A, Lopez S, et al.
Low-dose brachytherapy for early stage penile cancer: a 20-year single-institution study (73 patients).
Radiat Oncol. 2016; 11:96 [PubMed] Free Access to Full Article Related Publications
PURPOSE/OBJECTIVES: The aim of this study is to analyze the results of exclusive interstitial brachytherapy (IBT) as a conservative approach in the treatment of penile cancer confined to the glans or the shaft with long-term follow-up in a single institution.
MATERIALS/METHODS: Between July 1992 and November 2013, 73 consecutive patients with non-metastatic invasive penile cancer were treated by Low dose rate (LDR) IBT in our institution. The localization of the primary lesion was glands in 67 patients (91.8 %) and shaft in 6 patients (8.2 %). All 73 patients presented with squamous cell carcinoma with grades of differentiation as follows: 34 patients with grade 1 (44.7 %), 9 patients with grade 2 (11.8 %), 9 patients with grade 3 (11.8 %) and 21 patients unknown (28.8 %). Six patients (7.8 %) presented with in situ carcinoma, 55 patients (75,3 %) presented with T1, 11 patients (15 %) presented with T2, and one patient (1.3 %) presented with Tx. Inguinal nodal dissection was performed in 29 patients (38.2 %); 13 patients (17.8 %) presented with histologically confirmed positive ganglion. After circumcision, IBT was performed using a hypodermic needle. The median dose delivered was 60 Gy (range, 40 to 70 Gy). The median activity of the iridium-192 wire was 1.12 mCi/cm, and the median reference isodose rate was 0.4 Gy/h (range, 0.2-1.2). Patients with histological inguinal metastases received external beam radiotherapy to the selected inguinal affected area with a median dose of 45 Gy (30-55 Gy).
RESULTS: The median follow-up time was 51.8 months (range 34.4 to 68.7). The 5-year overall survival was 82.0 %, with eight deaths from cancer and five non-cancer-related deaths. Disease-specific survival was 91.4 %, relapse-free survival was 64.4 %, and local relapse-free survival as 74 %. Total or partial penile preservation was 87.9 % at 5-years. Complications rates at 5 years were 6.6 % urethral stenosis (five patients), two patients (2.6 %) with pain related to sexual intercourse and four patients (5.3 %) with dysuria grade 2. Five patients (6.8 %) required penile amputation for necrosis.
CONCLUSIONS: IBT provides good local control with organ preservation, excellent tolerance and low complication rates in early-stage penile cancers.

Brown PD, Jaeckle K, Ballman KV, et al.
Effect of Radiosurgery Alone vs Radiosurgery With Whole Brain Radiation Therapy on Cognitive Function in Patients With 1 to 3 Brain Metastases: A Randomized Clinical Trial.
JAMA. 2016; 316(4):401-9 [PubMed] Free Access to Full Article Related Publications
IMPORTANCE: Whole brain radiotherapy (WBRT) significantly improves tumor control in the brain after stereotactic radiosurgery (SRS), yet because of its association with cognitive decline, its role in the treatment of patients with brain metastases remains controversial.
OBJECTIVE: To determine whether there is less cognitive deterioration at 3 months after SRS alone vs SRS plus WBRT.
DESIGN, SETTING, AND PARTICIPANTS: At 34 institutions in North America, patients with 1 to 3 brain metastases were randomized to receive SRS or SRS plus WBRT between February 2002 and December 2013.
INTERVENTIONS: The WBRT dose schedule was 30 Gy in 12 fractions; the SRS dose was 18 to 22 Gy in the SRS plus WBRT group and 20 to 24 Gy for SRS alone.
MAIN OUTCOMES AND MEASURES: The primary end point was cognitive deterioration (decline >1 SD from baseline on at least 1 cognitive test at 3 months) in participants who completed the baseline and 3-month assessments. Secondary end points included time to intracranial failure, quality of life, functional independence, long-term cognitive status, and overall survival.
RESULTS: There were 213 randomized participants (SRS alone, n = 111; SRS plus WBRT, n = 102) with a mean age of 60.6 years (SD, 10.5 years); 103 (48%) were women. There was less cognitive deterioration at 3 months after SRS alone (40/63 patients [63.5%]) than when combined with WBRT (44/48 patients [91.7%]; difference, -28.2%; 90% CI, -41.9% to -14.4%; P < .001). Quality of life was higher at 3 months with SRS alone, including overall quality of life (mean change from baseline, -0.1 vs -12.0 points; mean difference, 11.9; 95% CI, 4.8-19.0 points; P = .001). Time to intracranial failure was significantly shorter for SRS alone compared with SRS plus WBRT (hazard ratio, 3.6; 95% CI, 2.2-5.9; P < .001). There was no significant difference in functional independence at 3 months between the treatment groups (mean change from baseline, -1.5 points for SRS alone vs -4.2 points for SRS plus WBRT; mean difference, 2.7 points; 95% CI, -2.0 to 7.4 points; P = .26). Median overall survival was 10.4 months for SRS alone and 7.4 months for SRS plus WBRT (hazard ratio, 1.02; 95% CI, 0.75-1.38; P = .92). For long-term survivors, the incidence of cognitive deterioration was less after SRS alone at 3 months (5/11 [45.5%] vs 16/17 [94.1%]; difference, -48.7%; 95% CI, -87.6% to -9.7%; P = .007) and at 12 months (6/10 [60%] vs 17/18 [94.4%]; difference, -34.4%; 95% CI, -74.4% to 5.5%; P = .04).
CONCLUSIONS AND RELEVANCE: Among patients with 1 to 3 brain metastases, the use of SRS alone, compared with SRS combined with WBRT, resulted in less cognitive deterioration at 3 months. In the absence of a difference in overall survival, these findings suggest that for patients with 1 to 3 brain metastases amenable to radiosurgery, SRS alone may be a preferred strategy.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00377156.

Li M, Huang XG, Yang ZN, et al.
Effects of omitting elective neck irradiation to nodal Level IB in nasopharyngeal carcinoma patients with negative Level IB lymph nodes treated by intensity-modulated radiotherapy: a Phase 2 study.
Br J Radiol. 2016; 89(1065):20150621 [PubMed] Article available free on PMC after 01/09/2017 Related Publications
OBJECTIVE: To investigate the need for elective neck irradiation (ENI) to nodal Level IB in patients with nasopharyngeal carcinoma (NPC) with negative Level IB lymph nodes (IB-negative) treated by intensity-modulated radiotherapy (IMRT).
METHODS: We conducted a Phase 2 prospective study in 123 newly diagnosed IB-negative patients with NPC treated by IMRT, who met at least 1 of the following criteria: (1) unilateral or bilateral Level II involvement with 1 of the following: Level IIA involvement or any Level II node ≥2 cm/with extracapsular spread; (2) ≥2 unilateral node-positive regions. Bilateral Level IB nodes were not contoured as part of the treatment target and treated electively. Level IB regional recurrence rate; pattern of treatment failure; 3-year overall survival (3y-OS), 3-year local control (3y-LC) and 3-year regional control (3y-RC) rates; toxicities; and dosimetric data for planning target volumes, organs at risk, Level IB and submandibular glands (SMGs) were evaluated.
RESULTS: Two patients developed failures at Level IB (1.6%). The 3y-LC, 3y-RC and 3y-OS rates were 93.5%, 93.5% and 78.0%, respectively. Bilateral Level IB received unplanned high-dose irradiation with a mean dose (Dmean) ≥50 Gy in 60% of patients. The average Dmean of bilateral SMGs was approximately 53 Gy.
CONCLUSION: ENI to Level IB may be unnecessary in IB-negative patients with NPC treated by IMRT. A further Phase 3 study is warranted.
ADVANCES IN KNOWLEDGE: Based on the results of this first Phase 2 study, we suggest omitting ENI to Level IB in Ib-negative patients with NPC with extensive nodal disease treated by IMRT.

Piroth MD, Galldiks N, Pinkawa M, et al.
Relapse patterns after radiochemotherapy of glioblastoma with FET PET-guided boost irradiation and simulation to optimize radiation target volume.
Radiat Oncol. 2016; 11:87 [PubMed] Article available free on PMC after 01/09/2017 Related Publications
BACKGROUND: O-(2-18 F-fluoroethyl)-L-tyrosine-(FET)-PET may be helpful to improve the definition of radiation target volumes in glioblastomas compared with MRI. We analyzed the relapse patterns in FET-PET after a FET- and MRI-based integrated-boost intensity-modulated radiotherapy (IMRT) of glioblastomas to perform an optimized target volume definition.
METHODS: A relapse pattern analysis was performed in 13 glioblastoma patients treated with radiochemotherapy within a prospective phase-II-study between 2008 and 2009. Radiotherapy was performed as an integrated-boost intensity-modulated radiotherapy (IB-IMRT). The prescribed dose was 72 Gy for the boost target volume, based on baseline FET-PET (FET-1) and 60 Gy for the MRI-based (MRI-1) standard target volume. The single doses were 2.4 and 2.0 Gy, respectively. Location and volume of recurrent tumors in FET-2 and MRI-2 were analyzed related to initial tumor, detected in baseline FET-1. Variable target volumes were created theoretically based on FET-1 to optimally cover recurrent tumor.
RESULTS: The tumor volume overlap in FET and MRI was poor both at baseline (median 12 %; range 0-32) and at time of recurrence (13 %; 0-100). Recurrent tumor volume in FET-2 was localized to 39 % (12-91) in the initial tumor volume (FET-1). Over the time a shrinking (mean 12 (5-26) ml) and shifting (mean 6 (1-10 mm) of the resection cavity was seen. A simulated target volume based on active tumor in FET-1 with an additional safety margin of 7 mm around the FET-1 volume covered recurrent FET tumor volume (FET-2) significantly better than a corresponding target volume based on contrast enhancement in MRI-1 with a same safety margin of 7 mm (100 % (54-100) versus 85 % (0-100); p < 0.01). A simulated planning target volume (PTV), based on FET-1 and additional 7 mm margin plus 5 mm margin for setup-uncertainties was significantly smaller than the conventional, MR-based PTV applied in this study (median 160 (112-297) ml versus 231 (117-386) ml, p < 0.001).
CONCLUSIONS: In this small study recurrent tumor volume in FET-PET (FET-2) overlapped only to one third with the boost target volume, based on FET-1. The shrinking and shifting of the resection cavity may have an influence considering the limited overlap of initial and relapse tumor volume. A simulated target volume, based on FET-1 with 7 mm margin covered 100 % of relapse volume in median and led to a significantly reduced PTV, compared to MRI-based PTVs. This approach may achieve similar therapeutic efficacy but lower side effects offering a broader window to intensify concomitant systemic treatment focusing distant failures.

Chen J, Liu P, Wang Q, et al.
Influence of Intensity-Modulated Radiation Therapy on the Life Quality of Patients with Nasopharyngeal Carcinoma.
Cell Biochem Biophys. 2015; 73(3):731-6 [PubMed] Related Publications
The present study intends to explore the influence of intensity-modulated radiation therapy on the quality of life for patients with nasopharyngeal carcinoma, which provides a theoretical basis and practical foundation for clinical practice. The present study randomly enrolled 130 cases of patients with nasopharyngeal carcinoma (NPC) in different stages who were admitted in The Second Affiliated Hospital of Fujian Medical University and the First Affiliated Hospital of Chongqing Medical University from September 2007 to August 2012, including 65 cases in IMRT group who received intensity-modulated radiation therapy and 65 cases in CRT group who received conventional radiation therapy. The prescribed dose in the target region of radical radiation therapy was 72 Gy/36 f; the prescribed dose in the target region at high risk was 60-64 Gy/30-32 f; the prescribed dose in the target region at low risk was 50-54 Gy/25-27 f and 2 Gy/f, with conventional fractionated irradiation of 1 f/d and 5 f/w. The data of the quality of life for patients with NPC who received intensity-modulated radiation therapy and conventional radiation therapy were collected and analyzed by filling in the questionnaire survey, including the Quality of Life Questionnaire of Head and Neck 35 (QLQ-H&N35) and Shot Form 36 Health Survey Questionnaire (SF-36). RP, VT, BP, SF, and RE scores in eight fields in SF-36 Scale were declined during the radiation therapy and risen again after radiation therapy, and those measured at 6 months after radiation therapy were higher than those before radiation therapy (all P < 0.05). The scores in IMRT group measured at two and six months after radiation therapy were all higher than those in CRT group (all P < 0.05). The scores of head and neck pain, pararthria, dysphagia, social difficulty, sensory difficulty, difficulty in feeding, xerostomia, cough, sticky saliva, and sensory discomfort during the radiation therapy were lower than those before radiation therapy (all P < 0.05). Except for the scores of sticky saliva and xerostomia, the other scores measured at 6 months after radiation therapy were all lower than those before radiation therapy, and the scores of dysphagia, sticky saliva, and xerostomia in MRT group were lower than those in CRT group (all P < 0.05). Conventional radiation therapy and intensity-modulated radiation therapy can cause a decline the quality of life for the patient with head and neck cancer, but intensity-modulated radiation therapy can improve local tumor control rate and significantly reduce the incidence of adverse reactions.

Okamoto S, Shiga T, Yasuda K, et al.
The reoxygenation of hypoxia and the reduction of glucose metabolism in head and neck cancer by fractionated radiotherapy with intensity-modulated radiation therapy.
Eur J Nucl Med Mol Imaging. 2016; 43(12):2147-2154 [PubMed] Related Publications
PURPOSE: The purpose of this study was to prospectively investigate reoxygenation in the early phase of fractionated radiotherapy and serial changes of tumoricidal effects associated with intensity-modulated radiation therapy (IMRT) in patients with head and neck cancer (HNC) using F-18 fluoromisonidazole (FMISO) PET and F-18 fluorodeoxyglucose (FDG) PET.
METHODS: Patients with untreated HNC underwent FMISO-PET and FDG-PET studies prospectively. A PET evaluation was conducted before each IMRT (Pre-IMRT), during IMRT (at 30 Gy/15 fr) (Inter-IMRT), and after completion of IMRT (70 Gy/35 fr) (Post-IMRT). FMISO-PET images were scanned by a PET/CT scanner at 4 h after the FMISO injection. We quantitatively analyzed the FMISO-PET images of the primary lesion using the maximum standardized uptake (SUVmax) and tumor-to-muscle ratio (TMR). The hypoxic volume (HV) was calculated as an index of tumor hypoxia, and was defined as the volume when the TMR was ≥ 1.25. Each FDG-PET scan was started 1 h after injection. The SUVmax and metabolic tumor volume (MTV) values obtained by FDG-PET were analyzed.
RESULTS: Twenty patients finished the complete PET study protocol. At Pre-IMRT, 19 patients had tumor hypoxia in the primary tumor. In ten patients, the tumor hypoxia disappeared at Inter-IMRT. Another seven patients showed the disappearance of tumor hypoxia at Post-IMRT. Two patients showed tumor hypoxia at Post-IMRT. The FMISO-PET results showed that the reduction rates of both SUVmax and TMR from Pre-IMRT to Inter-IMRT were significantly higher than the corresponding reductions from Inter-IMRT to Post-IMRT (SUVmax: 27 % vs. 10 %, p = 0.025; TMR: 26 % vs. 12 %, p = 0.048). The reduction rate of SUVmax in FDG-PET from Pre-IMRT to Inter-IMRT was similar to that from Inter-IMRT to Post-IMRT (47 % vs. 48 %, p = 0.778). The reduction rate of the HV in FMISO-PET from Pre-IMRT to Inter-IMRT tended to be larger than that from Inter-IMRT to Post-IMRT (63 % vs. 40 %, p = 0.490). Conversely, the reduction rate of the MTV in FDG-PET from Pre-IMRT to Inter-IMRT was lower than that from Inter-IMRT to Post-IMRT (47 % vs. 74 %, p = 0.003).
CONCLUSIONS: Both the intensity and the volume of tumor hypoxia rapidly decreased in the early phase of radiotherapy, indicating reoxygenation of the tumor hypoxia. In contrast, the FDG uptake declined gradually with the course of radiotherapy, indicating that the tumoricidal effect continues over the entire course of radiation treatment.

Nilsson G, Witt Nyström P, Isacsson U, et al.
Radiation dose distribution in coronary arteries in breast cancer radiotherapy.
Acta Oncol. 2016; 55(8):959-63 [PubMed] Related Publications
BACKGROUND: Women irradiated for left-sided breast cancer (BC) have an increased risk of coronary artery disease compared to women with right-sided BC. We describe the distribution of radiation dose in segments of coronary arteries in women receiving adjuvant radiotherapy (RT) for left- or right-sided BC.
MATERIAL AND METHODS: Fifteen women with BC, seven left-sided and eight right-sided, who had received three-dimensional conformal radiotherapy (3DCRT), constituted the study base. The heart and the segments of the coronary arteries were defined as separate organs at risk (OAR), and the mean and maximum radiation doses were calculated for each OAR.
RESULTS: In women with left-sided BC, irrespective of if regional lymph node RT was given or not, maximum dose in mid and distal left anterior descending artery (mdLAD) was approximately 50 Gy in 6/7 patients, whereas women with right-sided BC mainly received low doses of radiation. In women with left-sided BC, 6/7 patients had substantially higher mean dose to the distal LAD than to the heart, ranging from 30 to 55 Gy and 3 to13 Gy, respectively.
CONCLUSION: We found a pronounced difference of radiation dose distribution in the coronary arteries between women with left- and right-sided BC. Women with left-sided BC had almost full treatment dose in parts of mdLAD, regardless of if regional lymph node irradiation was given or not, while women with right-sided BC mainly received low doses to the coronary arteries.

Ben-David MA, Elkayam R, Gelernter I, Pfeffer RM
Melatonin for Prevention of Breast Radiation Dermatitis: A Phase II, Prospective, Double-Blind Randomized Trial.
Isr Med Assoc J. 2016 Mar-Apr; 18(3-4):188-92 [PubMed] Related Publications
BACKGROUND: Radiation-induced dermatitis is commonly seen during radiotherapy for breast cancer. Melatonin-based creams have shown a protective effect against ultraviolet-induced erythema and a radioprotective effect in rats.
OBJECTIVES: To evaluate the efficacy of melatonin-containing cream in minimizing acute radiation dermatitis.
METHODS: In this phase II, prospective, randomized, placebo-controlled double-blind study, patients who underwent breast-conserving surgery for stage 0-2 breast cancer were randomly allocated to melatonin emulsion (26 women) or placebo (21 women) for twice daily use during radiation treatment and 2 weeks following the end of radiotherapy. All women received 50 Gy whole breast radiation therapy with 2 Gy/fx using computed tomography-based 3D planning. Patients were examined and completed a detailed questionnaire weekly and 2 weeks following the end of treatment.
RESULTS: The occurrence of grade 1/2 acute radiation dermatitis was significantly lower (59% vs. 90%, P = 0.038) in the melatonin group. Women older than 50 had significantly less dermatitis than younger patients (56% vs. 100%, P = 0.021). The maximal radiation dermatitis in the study group was grade 2 in 15% of the treated patients.
CONCLUSIONS: Patients treated with melatonin-containing emulsion experienced significantly reduced radiation dermatitis compared to patients receiving placebo.

Deek MP, Nagarajan S, Kim S, et al.
Clinical characteristics and dose-volume histogram parameters associated with the development of pleural effusions in non-small cell lung cancer patients treated with chemoradiation therapy.
Acta Oncol. 2016; 55(8):1029-35 [PubMed] Related Publications
BACKGROUND: To investigate descriptive characteristics and dose metric (DM) parameters associated with development of pleural effusions (PlEf) in non-small cell lung cancer (NSCLC) treated with definitive chemoradiation therapy (CRT).
MATERIALS AND METHODS: We retrospectively assessed treatment records and follow-up imaging of 66 NSCLC patients to identify PlEf formation after CRT. PlEf association between mean heart dose (MHD), mean lung dose (MLD), heart V5-V60 (HV), and lung V5-V60 (LV) were evaluated using Cox Proportional Hazard Models.
RESULTS: A total of 52% (34 of 66 patients) of our population developed PlEf and the actuarial rates at 6 months, 12 months, and 18 months were 7%, 30%, and 42%, respectively. Median time to diagnosis was five months (range 0.06-27 months). The majority of PlEfs were grade one (67%) and developed at a median of four (0.06-13) months, followed by grade two (15%) at a median 11 (5-12) months, and grade three (18%) at a median of 11 (3-27) months. On multivariate analysis, increasing HV5-HV50, LV5-LV50, MHD, and MLD were associated with greater risk of PlEf. Higher grade PlEf was also associated with higher doses of radiation to the heart, while lung DM parameters were not significantly associated with higher PlEf grades. At five-months post-CRT, MHD of 25 Gy was associated with a 100% chance of grade one PlEf, an 82% risk of grade two PlEf, and a 19% risk of grade three PlEf.
CONCLUSIONS: Post-CRT PlEf is common in NSCLC with the majority being grade one. Increasing heart and lung irradiation was associated with increased risk of PlEf. Increasing heart irradiation also correlated with development of increasing grades of PlEf. The impact of potential cardiopulmonary toxicity and resultant PlEfs after CRT requires additional study.

Rasmusson E, Gunnlaugsson A, Kjellén E, et al.
Low-dose rate brachytherapy with I-125 seeds has an excellent 5-year outcome with few side effects in patients with low-risk prostate cancer.
Acta Oncol. 2016; 55(8):1016-21 [PubMed] Related Publications
BACKGROUND: Low-dose rate brachytherapy (LDR-BT) has been used in Sweden for more than a decade for treatment of low-risk prostate cancer. This study presents the outcome for patients treated with LDR-BT at a single institution with focus on the association between dose and biochemical failure-free survival (BFFS).
METHODS: In total 195 patients were treated with LDR-BT between 2004 and 2008. The patients were followed systematically for side effects for at least one year. PSA levels were followed regularly from three months and for at least five years. Outcome was analyzed in relation to clinical variables at baseline and to radiotherapy data.
RESULTS: Kaplan-Meier estimated BFFS at five years was 95.7%. Dose to the prostate in terms of D90% was significantly associated with BFFS [HR 0.90 (95%CI 0.83-0.96), p = 0.002].
CONCLUSION: Out data confirmed that absorbed dose is a predictive factor for BFFS for low-risk patients without androgen deprivation therapy. With our treatment routines and dosimetry, a D90% in the range of 170-180 Gy gives excellent outcomes with acceptable toxicity for patients with low-risk prostate cancer.

Swisher-McClure S, Yin L, Rosen M, et al.
Prospective MRI-based imaging study to assess feasibility of proton therapy for post-prostatectomy radiation.
Acta Oncol. 2016; 55(7):828-33 [PubMed] Related Publications
PURPOSE/OBJECTIVES: To optimize delivery of post-prostatectomy radiation (PPRT) with protons by examining dosimetric effects of variations in physician contouring, organ motion, and patient alignment during a course of PPRT.
MATERIAL AND METHODS: We enrolled 10 patients receiving PPRT in a prospective imaging study. All patients underwent combined computed tomography (CT)/magnetic resonance imaging (MRI) simulation with endorectal balloon (ERB) and received intensity modulated radiation therapy (IMRT) per institutional standards. Study patients underwent weekly MRI verification scans in the treatment position. Three radiation oncologists contoured clinical target volumes (CTV) on initial and verification scans using two consensus guidelines (RTOG and EORTC). We generated IMRT, double scattering (DS), and pencil beam scanning (PBS) proton plans and examined the dosimetric impact of contour variations, inter-fraction motion, and patient alignment techniques.
RESULTS: Inter-observer variations in contouring reduced median CTV coverage (D100) by 0.9% for IMRT plans, 2.8% for DS proton plans, 3.4-4.9% for PBS Proton Plans. Inter-fraction changes in target volumes due to internal organ motion resulted in a median loss of target dose coverage (D98) of 0% with IMRT, 3.5% with DS, and 8.1-8.3% with PBS. Median bladder V65Gy increased during the treatment course with all techniques (6.0-7.5%). Changes in the median rectal V60Gy remained small regardless of the treatment technique (0.5-3.1% increase). Alignment to the ERB after cranio-caudal bony alignment reduced CTV displacement compared to bony alignment alone, and as a result CTV coverage (D98) changed <2% with IMRT, DS, and PBS.
CONCLUSION: Proton-based treatments are more sensitive to changes in inter-fraction organ motion during PPRT compared to IMRT, and therefore motion management and patient alignment methods are critical. Patient alignment using bony anatomy as well as the ERB minimizes displacement of the CTV, and reduces variation in target dose coverage particularly for PBS proton therapy.

Giaddui T, Chen W, Yu J, et al.
Establishing the feasibility of the dosimetric compliance criteria of RTOG 1308: phase III randomized trial comparing overall survival after photon versus proton radiochemotherapy for inoperable stage II-IIIB NSCLC.
Radiat Oncol. 2016; 11:66 [PubMed] Article available free on PMC after 01/09/2017 Related Publications
BACKGROUND: To establish the feasibility of the dosimetric compliance criteria of the RTOG 1308 trial through testing against Intensity Modulation Radiation Therapy (IMRT) and Passive Scattering Proton Therapy (PSPT) plans.
METHODS: Twenty-six lung IMRT and 26 proton PSPT plans were included in the study. Dose Volume Histograms (DVHs) for targets and normal structures were analyzed. The quality of IMRT plans was assessed using a knowledge-based engineering tool.
RESULTS: Most of the RTOG 1308 dosimetric criteria were achieved. The deviation unacceptable rates were less than 10 % for most criteria; however, a deviation unacceptable rate of more than 20 % was computed for the planning target volume minimum dose compliance criterion. Dose parameters for the target volume were very close for the IMRT and PSPT plans. However, the PSPT plans led to lower dose values for normal structures. The dose parameters in which PSPT plans resulted in lower values than IMRT plans were: lung V5Gy (%) (34.4 in PSPT and 47.2 in IMRT); maximum spinal cord dose (31.7 Gy in PSPT and 43.5 Gy in IMRT); heart V5Gy (%) (19 in PSPT and 47 in IMRT); heart V30Gy (%) (11 in PSPT and 19 in IMRT); heart V45Gy (%) (7.8 in PSPT and 12.1 in IMRT); heart V50% (Gy) (7.1 in PSPT and 9.8 in IMRT) and mean heart dose (7.7 Gy in PSPT and 14.9 Gy in IMRT).
CONCLUSIONS: The revised RTOG 1308 dosimetric compliance criteria are feasible and achievable.

Truc G, Bernier V, Mirjolet C, et al.
A phase I dose escalation study using simultaneous integrated-boost IMRT with temozolomide in patients with unifocal glioblastoma.
Cancer Radiother. 2016; 20(3):193-8 [PubMed] Related Publications
PURPOSE: To evaluate the maximum tolerated dose of simultaneous integrated-boost intensity-modulated radiotherapy (SIB-IMRT) associated with temozolomide in patients with glioblastoma.
PATIENTS AND METHODS: Between November 2009 and January 2012, nine patients with malignant glioma were enrolled in this phase I clinical trial. Radiotherapy was delivered using fractions of 2.5Gy on the planning target volume b and of 1.9Gy on the planning target volume a. Volumes were defined as follow: gross tumour volume b: tumour taking up contrast on T1 weighted MRI images; clinical target volume b: gross tumour volume b+0.5cm (adapted to the anatomical structures) and lastly planning target volume b: clinical target volume b+0.5cm; gross tumour volume a: tumour (gross tumour volume b)+2cm and including oedema outlined on T2Flair MRI sequences; clinical target volume a gross tumour volume a+0.5cm (adapted to the anatomical structures); planning target volume a: clinical target volume a+0.5cm. Three patients were enrolled at each of the three levels of dose (70, 75 and 80Gy prescribed on the planning target volume b and 56, 60 and 60.8Gy on the planning target volume a). Radiotherapy was delivered with temozolomide according to the standard protocol. Dose-limiting toxicities were defined as any haematological toxicities at least grade 4 or as any radiotherapy-related non-haematological acute toxicities at least grade 3, according to the Common Terminology Criteria for Adverse Events, version 3.0.
RESULTS: Until the last dose level of 80Gy, no patient showed dose-limiting toxicity.
CONCLUSIONS: SIB-IMRT, at least until a dose of 80Gy in 32 daily fractions, associated with temozolomide is feasible and well tolerated.

Dubois N, Rio E, Ripoche N, et al.
Plasma ceramide, a real-time predictive marker of pulmonary and hepatic metastases response to stereotactic body radiation therapy combined with irinotecan.
Radiother Oncol. 2016; 119(2):229-35 [PubMed] Related Publications
BACKGROUND AND PURPOSES: Early biomarkers of tumour response are needed to discriminate between responders and non-responders to radiotherapy. We evaluated the ability of ceramide, a bioactive sphingolipid, to predict tumour sensitivity in patients treated by hypofractionated stereotactic body radiation therapy (SBRT) combined with irinotecan chemotherapy.
MATERIALS AND METHODS: Plasma levels of total ceramide and of its subspecies were measured before and during treatment in 35 patients with liver and lung oligometastases of colorectal cancer included in a phase II trial. Cer levels were quantified by LC-ESI-MS/MS and compared to tumour volume response evaluated one year later by CT-scan.
RESULTS: Pretreatment plasma ceramide levels were not indicative of tumour response. Nevertheless, the levels of total ceramide and of its 4 main subspecies were significantly higher at days 3 and 10 of treatment in objective responders than in non-responders. According to Kaplan-Meier curves, almost complete tumour control was achieved at 1year in patients with increased total ceramide levels whereas 50% of patients with decreased levels experienced an increase in tumour volume.
CONCLUSIONS: Total plasma ceramide is a promising biomarker of tumour response to SBRT combined with irinotecan that should enable to segregate patients with high risk of tumour escape.

Baumann BC, Nagda SN, Kolker JD, et al.
Efficacy and safety of stereotactic body radiation therapy for the treatment of pulmonary metastases from sarcoma: A potential alternative to resection.
J Surg Oncol. 2016; 114(1):65-9 [PubMed] Related Publications
BACKGROUND/OBJECTIVES: Oligometastatic sarcoma pulmonary metastases (PM) are typically treated with resection and/or chemotherapy. We hypothesize that stereotactic body radiotherapy (SBRT) can be an alternative to surgery that can achieve high rates of local control (LC) with limited toxicity.
METHODS: Thirty consecutive sarcoma patients received SBRT to 39 PM's from 2011 to 2015 at two university hospitals to a median dose of 50 Gy in 4-5 fractions with CyberKnife or linear accelerator. Patients underwent CT or PET/CT scans q3 months after SBRT.
RESULTS: 77% received prior chemotherapy, 70% had 1-3 prior pulmonary resections, and 26% received prior thoracic radiotherapy. Median lesion size was 2.4 cm (range 0.5-8.1 cm). Median follow-up was 16 and 23 months for patients alive at last follow-up. At 12 and 24 months, LC was 94% and 86%, and OS was 76% and 43%. LC and OS did not differ by SBRT technique, fractionation regimen, lesion location, histology, or size (all P > 0.05). Three developed grade 2 chest-wall toxicity with no other grade ≥2 toxicities.
CONCLUSIONS: This is the largest series on SBRT for sarcoma PM's and demonstrates that SBRT is well-tolerated with excellent LC across tumor locations and sizes. SBRT should be considered in these patients, and prospective studies are warranted. J. Surg. Oncol. 2016;114:65-69. © 2016 Wiley Periodicals, Inc.

Harada H, Fuji H, Ono A, et al.
Dose escalation study of proton beam therapy with concurrent chemotherapy for stage III non-small cell lung cancer.
Cancer Sci. 2016; 107(7):1018-21 [PubMed] Article available free on PMC after 01/09/2017 Related Publications
The purpose of this study is to determine the recommended dose (RD) of proton beam therapy (PBT) for inoperable stage III non-small cell lung cancer (NSCLC). We tested two prescribed doses of PBT: 66 Gy (relative biological effectiveness [RBE]) in 33 fractions and 74 Gy (RBE) in 37 fractions in arms 1 and 2, respectively. The planning target volume (PTV) included the primary tumor and metastatic lymph nodes with adequate margins. Concurrent chemotherapy included intravenous cisplatin (60 mg/m(2) , day 1) and oral S-1 (80, 100 or 120 mg based on body surface area, days 1-14), repeated as four cycles every 4 weeks. Dose-limiting toxicity (DLT) was defined as grade 3 or severe toxicities related to PBT during days 1-90. Each dose level was performed in three patients, and then escalated to the next level if no DLT occurred. When one patient developed a DLT, three additional patients were enrolled. Overall, nine patients (five men, four women; median age, 72 years) were enrolled, including six in arm 1 and three in arm 2. The median follow-up time was 43 months, and the median progression-free survival was 15 months. In arm 1, grade 3 infection occurred in one of six patients, but no other DLT was reported. Similarly, no DLT occurred in arm 2. However, one patient in arm 2 developed grade 3 esophageal fistula at 9 months after the initiation of PBT. Therefore, we determined that 66 Gy (RBE) is the RD from a clinical viewpoints. (Clinical trial registration no. UMIN000005585).

Ren XC, Wang QY, Zhang R, et al.
Accelerated hypofractionated three-dimensional conformal radiation therapy (3 Gy/fraction) combined with concurrent chemotherapy for patients with unresectable stage III non-small cell lung cancer: preliminary results of an early terminated phase II trial.
BMC Cancer. 2016; 16:288 [PubMed] Article available free on PMC after 01/09/2017 Related Publications
BACKGROUND: Increasing the biological effective dose (BED) of radiotherapy for non-small cell lung cancer (NSCLC) can increase local control rates and improve overall survival. Compared with conventional fractionated radiotherapy, accelerated hypofractionated radiotherapy can yield higher BED, shorten the total treatment time, and theoretically obtain better efficacy. However, currently, there is no optimal hypofractionated radiotherapy regimen. Based on phase I trial results, we performed this phase II trial to further evaluate the safety and preliminary efficacy of accelerated hypofractionated three-dimensional conformal radiation therapy(3-DCRT) combined with concurrent chemotherapy for patients with unresectable stage III NSCLC.
METHODS: Patients with previously untreated unresectable stage III NSCLC received 3-DCRT with a total dose of 69 Gy, delivered at 3 Gy per fraction, once daily, five fractions per week, completed within 4.6 weeks. At the same time, platinum doublet chemotherapy was applied.
RESULTS: After 12 patients were enrolled in the group, the trial was terminated early. There were five cases of grade III radiation esophagitis, of which four cases completed the radiation doses of 51 Gy, 51 Gy, 54 Gy, and 66 Gy, and one case had 16 days of radiation interruption. The incidence of grade III acute esophagitis in patients receiving an irradiation dose per fraction ≥2.7 Gy on the esophagus was 83.3% (5/6). The incidence of symptomatic grade III radiation pneumonitis among the seven patients who completed 69 Gy according to the plan was 28.6% (2/7). The median local control (LC) and overall survival (OS) were not achieved; the 1-year LC rate was 59.3%, and the 1-year OS rate was 78.6%.
CONCLUSION: For unresectable stage III NSCLC, the accelerated hypofractionated radiotherapy with a total dose of 69 Gy (3 Gy/f) combined with concurrent chemotherapy might result in severe radiation esophagitis and pneumonitis to severely affect the completion of the radiotherapy. Therefore, we considered that this regimen was infeasible. During the hypofractionated radiotherapy with concurrent chemotherapy, the irradiation dose per fraction to esophagus should be lower than 2.7 Gy. Further studies should be performed using esophageal tolerance as a metric in dose escalation protocols.
TRIAL REGISTRATION: NCT02720614, the date of registration: March 23, 2016.

Lutkenhaus LJ, Vestergaard A, Bel A, et al.
A biological modeling based comparison of two strategies for adaptive radiotherapy of urinary bladder cancer.
Acta Oncol. 2016; 55(8):1009-15 [PubMed] Related Publications
Background Adaptive radiotherapy is introduced in the management of urinary bladder cancer to account for day-to-day anatomical changes. The purpose of this study was to determine whether an adaptive plan selection strategy using either the first four cone beam computed tomography scans (CBCT-based strategy) for plan creation, or the interpolation of bladder volumes on pretreatment CT scans (CT-based strategy), is better in terms of tumor control probability (TCP) and normal tissue sparing while taking the clinically applied fractionation schedules also into account. Material and methods With the CT-based strategy, a library of five plans was created. Patients received 55 Gy to the bladder tumor and 40 Gy to the non-involved bladder and lymph nodes, in 20 fractions. With the CBCT-based strategy, a library of three plans was created, and patients received 70 Gy to the tumor, 60 Gy to the bladder and 48 Gy to the lymph nodes, in 30-35 fractions. Ten patients were analyzed for each adaptive plan selection strategy. TCP was calculated applying the clinically used fractionation schedules, as well as a rescaling of the dose from 55 to 70 Gy for the CT-based strategy. For rectum and bowel, equivalent doses in 2 Gy fractions (EQD2) were calculated. Results The CBCT-based strategy resulted in a median TCP of 75%, compared to 49% for the CT-based strategy, the latter improving to 72% upon rescaling the dose to 70 Gy. A median rectum V30Gy (EQD2) of 26% [interquartile range (IQR): 8-52%] was found for the CT-based strategy, compared to 58% (IQR: 55-73%) for the CBCT-based strategy. Also the bowel doses were lower with the CT-based strategy. Conclusions Whereas the higher total bladder TCP for the CBCT-based strategy is due to prescription differences, the adaptive strategy based on CT scans results in the lowest rectum and bowel cavity doses.

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