Gy External Beam Radiotherapy Research Articles

Eradicative brachytherapy with hyaluronate gel injection into pararectal space in treatment of bulky vaginal stump recurrence of uterine cancer

The purpose of this study is to develop a procedure for eradicative brachytherapy that can deliver a curative boost dose to bulky (>4 cm) vaginal stump recurrence of uterine cancer without risk of damaging surrounding organs. We separated risk organs (the rectum and sigmoid) from the target during brachytherapy, with a hyaluronate gel injection into the pararectal space via the percutaneous paraperineal approach under local anesthesia. The rectum anchored to the sacrum by native ligament was expected to shift posteriorly. We encountered a patient with bulky stump recurrence of uterine cancer, approximately 8 cm in maximum diameter. She was complaining of abdominal pain and constipation due to bowel encasement. Following 50 Gy of external beam radiotherapy, we applied a single fraction of brachytherapy under gel separation and delivered 14.5 Gy (50.8 GyE: equivalent dose in 2-Gy fraction calculated with linear quadratic model at α/β = 3) to the target. The gel injection procedure was completed in 30 min without complications. A total irradiation dose of 100.8 GyE was delivered to the target and the cumulative minimum dose to the most irradiated rectosigmoidal volume of 2 cc (cumulative D2cc) was calculated as 58.5 GyE with gel injection, and was estimated to be 96 GyE without. Over three years, the local stump tumor has completely disappeared, with no complications. Brachytherapy with a pararectal gel injection can be a safe and effective eradicative option for bulky vaginal stump recurrence.

Intratumoral Gene Therapy Injections with a Multipronged, Multi–Side Hole Needle for Rectal Carcinoma

Interventional radiologists can deliver therapeutics directly to a tumor via needle injection. One of the major limitations of directly injected gene therapies is limited delivery, penetration, and transfection efficiency of the genetic vector, which in many cases directly limits the therapeutic effect. Numerous preclinical oncology models exist which rely upon direct injection of DNA plasmid or vector through an end-hole needle and into a tumor. Selection of a physically more efficient device with more needles and more side holes could improve distribution of the therapeutic agent.[1] Small hepatocellular carcinomas have been effectively treated with alcohol injections via a multi-pronged, multi-side hole needle. [2] TNFerade (GenVec, Gaithersburg, MD) is an attenuated adenovirus vector whose cargo is the gene encoding for tumor necrosis factor-alpha (TNFα), a potent cytokine that can be tumorocidal and also makes nearby tumor cells more sensitive to chemotherapy and to radiation therapy. TNFerade is turned on by a promoter that is turned on by radiation. [3] TNFerade also causes a “bystander effect” whereby affected cells do not necessarily need to be transfected with virus, but can respond to the TNFα product programmed by the gene. Despite the bystander effect, injectable therapeutics may suffer from lack of exposure to tumor tissue or a limited distribution in target tumor. Optimizing the physical distribution of such a therapeutic agent should be a goal of the interventional radiologist performing direct gene therapy injections. 5 patients with T3, T4, or N+ rectal cancer were treated as part of a clinical trial with weekly transrectal ultrasound (TRUS) guided injections, monitored under direct TRUS visualization [fig 1]. Patients received injections via a Quadrafuse needle (Rex Medical, Conshohocken, PA & Alliance Medical, Austin, TX) [fig 1] with three prongs, each with three side holes, or a custom Bernardino needle (Cook Medical, Bloomington, IN) with three side holes. Five weekly injections of 4 × 1010 particle units TNF-erade were combined with 50.4 Gy of external beam radiation, chemotherapy with capecitibine, and surgical resection. No complications were seen from the 25 injection procedures in 5 patients. [3] Fig 1 Multi-prong, multi-side hole needle in rectal cancer monitoring gene therapy injection with ultrasound. Ultrasound shows central cannula (open arrow) has deployed prong (closed arrow) with side holes, to better distribute therapeutic agent. Direct injection of gene therapy is highly inefficient, which may limit transfection and theoretically limit therapeutic efficacy. Interventional radiologists should consider the speculative benefits of multi-pronged and multi-side hole needles when directly injecting gene therapies.

Serial Assessment of Lymphocytes and Apoptosis in the Prostate During Coordinated Intraprostatic Dendritic Cell Injection and Radiotherapy

Local radiotherapy plus intratumoral syngeneic dendritic cell injection can mediate apoptosis/cell death and immunological tumor eradication in murine models. A novel method of coordinated intraprostatic, autologous dendritic cell injection together with radiation therapy was prospectively evaluated in five HLA-A2(+) subjects with high-risk, localized prostate cancer, using androgen suppression, 45 Gy external beam radiation therapy in 25 fractions over 5 weeks, dendritic cell injections after fractions 5, 15 and 25 and then interstitial radioactive seed placement. Serial prostate biopsies before and during treatment showed increased apoptotic cells and parenchymal distribution of CD8(+) cells. CD8(+) T-cell responses to test peptides were assessed using an enzyme-linked immunosorbent spot IFN-γ production assay, demonstrating some prostate cancer-specific protein-derived peptides associated with increased titer. In conclusion, the technique was feasible and well-tolerated and specific immune responses were observable. Future trials could further test the utility of this approach and improve on temporal coordination of intratumoral dendritic cell introduction with particular timelines of therapy-induced apoptosis.

A Novel Modular Polymer Platform for the Treatment of Head and Neck Squamous Cell Carcinoma in an Animal Model<alt-title>Novel Modular Polymer Platform</alt-title>

To evaluate the therapeutic efficacy of a novel modular polymer platform in the treatment of head and neck squamous cell carcinoma (HNSCC). In vivo study. Academic research laboratory. Subjects and C3H/HeJ mice and SCID/beige mice were randomized to receive implantation of no polymer, plain polymer, plain polymer with local cisplatin injection, or cisplatin polymer. The 2 groups of mice implanted with cisplatin polymer or no polymer were further randomized to receive 4 Gy of external beam radiation for 4 days or no radiation. Tumor size was measured until the mice were humanely killed. At necropsy, the tumors were excised and weighed. There was a significant reduction in tumor growth using this novel polymer platform. The cisplatin-secreting polymer effectively reduced human head and neck tumor growth in SCID mice by 17-fold and SCC VII/SF tumors in C3H/HeJ mice by more than 16-fold compared with the control, plain polymer, and plain polymer+intratumoral cisplatin injection groups (P=.01 for both). We also observed a statistically significant lower tumor weight in mice treated with cisplatin polymer and concomitant radiation compared with the radiation alone and control groups. We demonstrate the efficacy of a novel polymer platform in delivering cisplatin to a partially resected SCC in a murine model. This polymer may represent a new therapeutic modality for patients with HNSCC. Once this polymer platform is optimized, we will plan for validation in the context of a prospective trial in patients with unresectable advanced or recurrent HNSCC.

Orbital MALT Lymphoma, Abdominal Hodgkin lymphoma, and Systemic Diffuse Large B-cell Lymphoma Develop Sequentially in One Patient

In February 2002, a 42-year-old woman developed ocular adnexal extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT), MALT lymphoma, in the bilateral orbits involving lacrimal glands. She underwent 30 Gy external beam irradiation to the orbital lesions on both sides. She was well until November 2008 when she developed abdominal lymphadenopathy and transabdominal excisional biopsy showed mixed cellularity classical Hodgkin lymphoma at stage II. She underwent standard combination chemotherapy. In July 2010, she developed systemic lymphadenopathy and was diagnosed with diffuse large B-cell lymphoma (DLBCL) by cervical lymph node biopsy. She underwent rituximab monotherapy and finally allogeneic hematopoietic stem cell transplantation in October 2010, but died of renal failure in February 2011. Amplification by polymerase chain reaction of the immunoglobulin heavy chain gene gave rise to dominant discrete fragments of the same size between the orbital lesion with MALT lymphoma in 2002 and the cervical lymph node lesion with DLBCL in 2010. The sequential development of MALT lymphoma, Hodgkin lymphoma, and DLBCL in the long-term course of this patient suggests the common origin of the neoplastic cells, changing their pathological faces in response to irradiation and combination chemotherapy.

20 Gy Versus 44 Gy of Supplemental External Beam Radiotherapy With Palladium-103 for Patients With Greater Risk Disease: Results of a Prospective Randomized Trial

The necessity of external beam radiotherapy (EBRT) as a supplement to prostate brachytherapy remains unknown. We report brachytherapy outcomes for patients with higher risk features randomized to substantially different supplemental EBRT regimens. Between December 1999 and June 2004, 247 patients were randomized to 20 Gy vs. 44 Gy EBRT followed by a palladium-103 boost (115 Gy vs. 90 Gy). The eligibility criteria included clinically organ-confined disease with Gleason score 7-10 and/or pretreatment prostate-specific antigen (PSA) level 10-20 ng/mL. The median follow-up period was 9.0 years. Biochemical progression-free survival (bPFS) was defined as a PSA level of ≤0.40 ng/mL after nadir. The median day 0 prescribed dose covering 90% of the target volume was 125.7%; 80 men received androgen deprivation therapy (median, 4 months). Multiple parameters were evaluated for their effect on bPFS. For the entire cohort, the cause-specific survival, bPFS, and overall survival rates were 97.7%, 93.2%, and 80.8% at 8 years and 96.9%, 93.2%, and 75.4% at 10 years, respectively. The bPFS rate was 93.1% and 93.4% for the 20-Gy and 44-Gy arms, respectively (p = .994). However, no statistically significant differences were found in cause-specific survival or overall survival were identified. When stratified by PSA level of ≤10 ng/mL vs. >10 ng/mL, Gleason score, or androgen deprivation therapy, no statistically significant differences in bPFS were discerned between the two EBRT regimens. On multivariate analysis, bPFS was most closely related to the preimplant PSA and clinical stage. For patients with biochemically controlled disease, the median PSA level was <0.02 ng/mL. The results of the present trial strongly suggest that two markedly different supplemental EBRT regimens result in equivalent cause-specific survival, bPFS, and overall survival. It is probable that the lack of benefit for a higher supplemental EBRT dose is the result of the high-quality brachytherapy dose distributions.

Poly(ADP-ribose) polymerase inhibitors combined with external beam and radioimmunotherapy to treat aggressive lymphoma

To assess the possible radiosensitizing capabilities of two different poly(ADP-ribose) polymerase (PARP) inhibitors in combination with external beam and I-tositumomab in a non-Hodgkin's lymphoma cell line. Epstein-Barr virus-infected human Raji lymphoma cells with lentivirally transfected green fluorescent protein and luciferase in log-phase growth were incubated with various doses of AZD-2281 and ABT-888 24 h before external beam radiation exposure. A 500 nmol/l concentration of AZD-2281 and ABT-888 was used to assess the growth curve of Raji lymphoma cells over 5 days. The number of double-stranded breaks was visually assessed using a H2AX antibody and confocal microscopy. Intracellular PARP activity was measured 2 h after incubation with AZD-2281 (500 nmol/l) and ABT-888 using a colorimetric PARP assay kit. The radiosensitizing effect of AZD-2281 (500 nmol/l) with various doses of I-tositumomab was assessed after 24 h. A volume of 500 nmol/l of AZD-2281 and 500 nmol/l of ABT-888, in combination with 0, 4, 8, and 12 Gy external beam radiation, showed a 5.2, 7.1, 10.1, and 33.1% radiosensitization. A measure of 500 nmol/l AZD-2281 and ABT-888 significantly reduced the percentage of viable cells on days 3-5 compared with controls. The maximal relative reduction in viable cells was 78.5%, and this occurred with AZD-2281 (500 nmol/l) on day 5. AZD-2281 revealed a higher number of double-stranded breaks with confocal microscopy than did ABT-888. Two hours after incubation of Raji cells with 500 nmol/l of AZD-2281 or ABT-888, the colorimetric PARP activity assay showed a reduction of 30.36% with ABT-888 and of 47.8% with AZD-2281. Combining AZD-2281 (500 nmol/l) with 0, 5 μCi (0.185 MBq), 10 μCi (0.37 MBq) and 20 μCi (0.74 MBq) ¹³¹I-tositumomab revealed a significant reduction in cell viability after 24 h with 5 μCi (0.185 MBq) (P<0.01) and 10 μCi (0.37 MBq) (P<0.01) radiation dose. PARP inhibitors AZD-2281 and ABT-888 are highly radiosensitizing agents when used before external beam radiation and ¹³¹I-tositumomab.

Is single fraction 15 Gy the preferred high dose-rate brachytherapy boost dose for prostate cancer?

Background and purposeHigh dose-rate (HDR) brachytherapy is most commonly administered as a boost in two or more fractions combined with external beam radiotherapy (EBRT). Our purpose is to compare outcomes with a single fraction HDR boost to that with a standard fractionated boost in intermediate risk prostate cancer. Materials and methodsResults of two sequential phase II clinical trials are compared. The Single Fraction protocol consists of 15Gy HDR in one fraction followed by 37.5Gy EBRT in 15 fractions over 3weeks; the Standard Fractionation protocol consisted of two HDR fractions each of 10Gy, 1week apart, followed by 45Gy EBRT in 25 fractions. Patients had intermediate risk disease, and were well balanced for prognostic factors. Patients were followed prospectively for efficacy, toxicity and health-related quality of life (Expanded Prostate Index Composite). Efficacy was assessed biochemically using the Phoenix definition, and by biopsy at 2years. ResultsThe Single Fraction protocol accrued 123 patients and the Standard Fractionation protocol, 60. With a median follow-up of 45 and 72months, respectively, the biochemical disease-free survival was 95.1% and 97.9% in the Single and Standard Fractionation trials (p=0.3528). Two-year prostate biopsy was positive in only 4% and 8%, respectively. There was no difference in late urinary or rectal toxicity rates, or in health-related quality of life between the two protocols. ConclusionsThe Single Fraction HDR protocol results in high disease control rate and low toxicity similar to our previous protocol using two HDR insertions, with significant savings in resources. While mature results with longer follow-up are awaited, a single 15Gy may be considered as a standard fractionation regimen in combination with EBRT for men with intermediate risk disease.

Combination external beam radiation and brachytherapy boost with androgen deprivation for treatment of intermediate-risk prostate cancer: long-term results of CALGB 99809.

Combined transperineal prostate brachytherapy and external beam radiation therapy (EBRT) is widely used for treatment of prostate cancer. Long-term efficacy and toxicity results of a multicenter phase 2 trial assessing combination of EBRT and transperineal prostate brachytherapy boost with androgen deprivation therapy (ADT) for intermediate-risk prostate cancer are presented. Intermediate-risk patients per Memorial Sloan-Kettering Cancer Center/National Comprehensive Cancer Network criteria received 6 months of ADT, and 45 grays (Gy) EBRT to the prostate and seminal vesicles, followed by transperineal prostate brachytherapy with I125 (100 Gy) or Pd103 (90 Gy). Toxicity was graded using the National Cancer Institute Common Toxicity Criteria version 2 and Radiation Therapy Oncology Group late radiation morbidity scoring systems. Disease-free survival (DFS) was defined as time from enrollment to progression (biochemical, local, distant, or prostate cancer death). In addition to the protocol definition of biochemical failure (3 consecutive prostate-specific antigen rises>1.0 ng/mL after 18 months from treatment start), the 1997 American Society for Therapeutic Radiology and Oncology (ASTRO) consensus and Phoenix definitions were also assessed in defining DFS. The Kaplan-Meier method was used to estimate DFS and overall survival. Sixty-one of 63 enrolled patients were eligible. Median follow-up was 73 months. Late grade 2 and 3 toxicity, excluding sexual dysfunction, occurred in 20% and 3% of patients. Six-year DFS applying the protocol definition, 1997 ASTRO consensus, and Phoenix definitions was 87.1%, 75.1%, and 84.9%. Six deaths occurred; only 1 was attributed to prostate cancer. Six-year overall survival was 96.1%. In a cooperative setting, combination of EBRT and transperineal prostate brachytherapy boost plus ADT resulted in excellent DFS with acceptable late toxicity for patients with intermediate-risk prostate cancer.

Optimal Duration of Androgen Deprivation in Combination with Radiation Therapy for Japanese Men with High-Risk Prostate Cancer

Objectives: To evaluate the efficacy and toxicity of external beam radiation therapy (EBRT) combined with androgen deprivation therapy (ADT) for Japanese high-risk prostate cancer (PCa) patients in a single institution. Methods: Seventy-five high-risk PCa patients were treated by three-dimensional conformal radiotherapy of 70 Gy combined with neoadjuvant, concurrent and adjuvant ADT. Results: Median age was 72 (59–82) years. Median initial serum prostate-specific antigen (PSA) was 19.0 (4.7–200) ng/ml. Median duration of the entire ADT was 27 (8–63) months. Median follow-up after initiating ADT and after completing EBRT was 66 (41–105) and 59 (36–94) months, respectively. Five-year overall, clinical progression-free, and biochemical progression-free survival rates were 98.3, 97.2, and 87.4%; 2 (2.7%) cancer deaths, 3 (4.0%) clinical progressions, and 11 (14.7%) biochemical progressions. Multivariate analysis suggested a total duration of ADT shorter than 24 months as an independent risk factor of biochemical progression (p = 0.01). Grade 3 toxicities related to EBRT were observed: 1 patient with proctitis and rectal bleeding and 1 patient with rectal bleeding. Conclusions: It is suggested that 70 Gy EBRT combined with ADT confers disease-free survival benefit with tolerable adverse events for Japanese high-risk PCa patients. ADT of 24 months or longer might be recommended to minimize biochemical progression.

SU‐E‐T‐392: Using Deformable Registration to Evaluate Combined Biological Effective Dose in Patients Receiving Combination External Beam Radiotherapy and Brachytherapy of Prostate Cancer Patients

Purpose: To determine the feasibility of combining external beam radiotherapy (EBRT) and brachytherapy (BT) in terms of Biological Effective Dose (BED) using deformable image registration to evaluate treatment. Methods: This study analyzed combined EBRT and BT treatments of prostate cancer. Each patient received 45 Gy EBRT IMRT or VMAT technique prescribed to a planning target volume (PTV) followed by a 110 Gy or 100 Gy BT boost using I‐125 or Pd‐103, respectively. EBRT planning CT and post‐implant CT were co‐registered using rigid/deformable registration. The BT dose matrix was mapped via deformable transformation component to the EBRT CT study. The seed dose distribution was combined with the EBRT CT by the re‐sampling of the dose matrix. BED calculations were performed utilizing the linear quadratic model assuming &amp;#945;/&amp;#946; ratio of 2 to convert EBRT and BT dose distributions. This yields evaluable topographical dose volume histogram (DVH) for evaluation of dosage to the PTV and organs at risk (OAR). Results: Twenty seven patient plans were successfully reconstructed to yield combined BED information. The average EBRT BED was found to be 85 Gy and the BT BED average was to be 127 (range 100–155 Gy) for a combined total average dose of 212 (range 185–240 Gy). The combined V0.1cc and V2cc of OAR were evaluated in both conventional and a novel topographical technique. Conclusions: We found it feasible to combine EBRT and BT treatment plans for BED analysis of both target and OAR. This allows for a novel and dynamic evaluation of combined therapy. BED distribution can enable clinicians to identify areas where failure can occur and assess areas of potential toxicity, currently not possible using physical dose summation. It can also be used as a tool for physicians to objectively assess the quality of treatment plans and for multi institutional comparisons.

Abstract 1483: Metastatic characteristics and radiosensitivity of thyroid carcinoma cells depends on HIF-1 and PI3K signaling in vitro and in vivo

Abstract The purpose of this study was to determine the importance of the HIF-1 and PI3K pathways in the development of a) a metastatic phenotype and b) desensitization to radiotherapy, in thyroid carcinomas. In vitro scratch wound migration assays and cell spreading assays were performed under various oxygen tensions in the presence or absence of two PI3K inhibitors PI-103 and GDC-0941 (GDC-0941 is currently in clinical trials). The role of HIF-1α and PI3K on these processes was also assessed via genetic inhibition of HIF-1α and PI3K by use of a dominant negative variant (dnHIF) and by over expressing WT PTEN in PTEN-null FTC133 cells. For in vivo studies, follicular (FTC133) and anaplastic (8505c) thyroid carcinoma cells were manufactured to stably express eGFP and implanted sub-cutaneously. Mice were treated with PI-103 and GDC-0941 by intra-peritoneal injection and oral gavage. Spontaneous metastatic colonization to the lungs was confirmed by viewing eGFP postive colonies cultured from digested lung tissue and further by immuno-blotting for eGFP. For irradiation studies, cells were exposed to 0,2,4,6 GY external beam radiation. Both PI3K and hypoxia increased cell migration, cell adhesion and cell spreading on extra-cellular matrix molecules. These processes are key in the development of a metastatic phenotype. Genetic and pharmacological inhibition of both PI3K and HIF-1α reduced the migratory, adhesive and cell spreading potential of thyroid carcinoma cells under varying oxygen tensions. Additionally, pharmacological and genetic inhibition of PI3K and HIF-1α reduced both PI3K and HIF-1 activity resulting in reduced activation of PI3K target proteins (pAKT, pGSK-3β) and reduced expression of HIF-1 target genes (CA-9, VEGF, LDH-A, GLUT-1). In vivo, PI-103 and GDC-0941 reduced PI3K and HIF-1α activity as well as PI3K and HIF-1 target genes in primary follicular and anaplastic tumors. Importantly, mice bearing dnHIF-FTC133 tumors and those treated with GDC-0941 had reduced number of metastatic colonies in the lungs of follicular thyroid tumor bearing mice. Radiation induced HIF-1α activity and expression. GDC-0941 combined with radiation blocked HIF-1 induction, prolonged DNA double-strand breaks and reduced clonogenic survival suggesting a radio-sensitising effect. These data link PI3K, HIF-1 activation and aggressive disease in thyroid carcinoma and suggest PI3K may be an important therapeutic target. One attractive approach would be combination therapy with external beam radiation. The latter is the first line treatment in patients suffering from anaplastic thyroid carcinoma but is seldom successful. With the known desensitizing effects of HIF-1 and PI3K activity on radiation treatment, a combined approach involving both radiation and a PI3K inhibitor may improve both the therapeutic response within the local tumor and reduce metastatic potential. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1483. doi:10.1158/1538-7445.AM2011-1483

Moderate dose escalation with single-fraction high-dose-rate brachytherapy boost for clinically localized intermediate- and high-risk prostate cancer: 5-year outcome of the first 100 consecutively treated patients

Purpose To analyze the clinical outcome and toxicity data of the first 100 consecutive patients treated with a single-fraction high-dose-rate brachytherapy (HDR-BT) and external beam radiotherapy (EBRT). Methods and Materials Two-hundred eighty patients have been treated with HDR-BT boost for localized intermediate- to high-risk prostate cancer. Among these, the outcome and toxicity of the first 100 patients treated with a single HDR-BT fraction were assessed. A median dose of 60 Gy EBRT was given to the prostate and vesicles. Interstitial HDR-BT of 10 Gy was performed during the course of EBRT. Results Median followup time was 61.5 months. The 5-year actuarial rates of overall survival, cause-specific survival, disease-free survival, and biochemical no evidence of disease (bNED) for the entire cohort were 93.3%, 99.0%, 89.3%, and 85.5%, respectively. The 7-year actuarial rate of bNED was 84.2% for the intermediate-risk group and 81.6% for the high-risk group ( p = 0.8464). The 7-year actuarial rates of bNED for Grade 1, 2, and 3 tumors were 97.5%, 80.0%, and 67.1%, respectively. The 5-year probability for developing late Grade 3 gastrointestinal and genitourinary (GU) toxicity was 2.1% and 14.4%, respectively. Grade 3 GU complications occurred significantly more frequently in patients with a history of preirradiation transurethral resection (29.1% vs. 8.8%; p = 0.0047). Conclusions Five-year outcome after 60 Gy EBRT plus a single fraction of 10 Gy HDR-BT boost is encouraging. Preradiation transurethral resection significantly increases the risk of late severe GU complications.

Definitive Chemoradiation for Oesophageal Cancer — a Standard of Care in Patients with Non-metastatic Oesophageal Cancer

Aims A retrospective analysis was carried out of 291 cases of oesophageal cancer treated with definitive chemoradiotherapy (dCRT) at a single UK cancer centre between 1995 and 2009. Our protocol consisted of two cycles of neoadjuvant platinum-based chemotherapy followed by two further cycles given concurrently with 50 Gy of external beam radiotherapy delivered in 25 fractions over 5 weeks. Materials and methods Demographic, patient and outcome data were recorded prospectively through an electronic health record and retrospectively analysed, using appropriate statistical tools. Results Data on 266 patients were available for analysis. The median age was 66.6 years, 53% were adenocarcinomas. dCRT was used instead of surgery because of age/co-morbidity in 44% and disease extent in 39%. Ninety-three per cent of patients completed treatment according to protocol. Grade 3 and 4 toxicities were seen in 42 and 7%, respectively. Median survival was 20.6 months; 2, 3 and 5 year survival rates were 43.6, 32.9 and 19.5%, respectively. Advanced disease was associated with a worse outcome. Shorter disease length was associated with a better median survival, but some patients with disease >10 cm had long-term disease control. The effect of other patient- and disease-related factors was also analysed. Conclusion We present data showing that dCRT is well tolerated and should be considered as an alternative to surgery for all patients with locally advanced oesophageal cancer, not only those with co-morbidity. Furthermore, the benefits of dCRT are not confined to carcinomas with squamous histology.

Open MR-Guided High-Dose-Rate (HDR) Prostate Brachytherapy: Feasibility and Initial Experiences Open MR-Guided High-Dose-Rate (HDR) Prostate Brachytherapy

The aim of our pilot study was to demonstrate the feasibility and dosimetric quality of MR-guided HDR prostate brachytherapy in a low-field 0.35T open MRI scanner and to present our initial clinical experiences. 16 patients with intermediate- to high-risk localized prostate cancer were treated with 46-60 Gy of external beam radiotherapy preceded and/or followed by an 8 Gy MR-guided HDR boost. For interventions an MR compatible custom-made system, coaxial needles and plastic catheters were used. Template reconstruction, trajectory planning, image guidance, contouring and treatment planning were exclusively based on MR images. For treatment planning, dose-point- and anatomy-based inverse planning optimization was used. Image quality was found to be good to excellent in almost all cases. The mean catheter placement accuracy modeled by Rayleigh distribution was 2.9 mm with a sigma value of 2.3 mm. The mean and standard deviation (SD) of the dosimetric results for the target volume were the following: V100: 94.2 ± 4.3%, V150: 43.9 ± 6.8%, V200: 18.5 ± 5.9%. The mean D(0.1), D(1) and D1 values for the intraprostatic urethra were 117.6 ± 12.5%, 98.5 ± 19.9% and 122.3 ± 16.4%, respectively. Regarding the rectal wall the mean D(0.1), D(1) and D(2) values were 77.3 ± 7.2%, 64.8 ± 7.5%, and 53.2 ± 9.1%, respectively. The mean maximum dose for the inner rectal surface was 53.5 ± 9.2%. No RTOG Grade 3 or worse acute toxicities were observed. Our method seems to be a promising approach for performing feasible, accurate and high-quality MR-guided HDR prostate brachytherapy. To determine the long term side effects and outcome higher number of patients, additional follow-up is needed.

Dose response relationship of nuclear changes with fractionated radiotherapy in assessing radiosensitivity of Oral Squamous Cell Carcinoma

Radiotherapy is frequently used as treatment for oral cancer either alone or in combination with surgery. Reaction of tumor tissue to radiotherapy often shows marked inter-individual variability making it difficult to assess and pre dict the treatment outcome for individual patients. Recently attention has been drawn towards the role of radiation induced nuclear changes to assess radiosensitivity. Objectives: To establish the relationship between various nuclear changes with radiation dose and to explore the possibility of utilizing them as an assay to predict tumor response to radiotherapy. Study Design: Study group consisted of 20 patients with histologically proven oral squamous cell carcinoma treated by fractionated radiotherapy, receiving a total of 60 Gy of external beam radiation in 30 fractions of 2 Gy each given daily. Serial scrape smears were collected from the lesion and contralateral normal site before the start of treatment and after 4th, 8th, and 12th fraction. Staining with acridine orange fluorescent dye and May-Grunwald Giemsa stain was done to assess nuclear abnormalities like micronucleation, nuclear budding, binucleation, and multinucleation. These were then correlated with tumor response. Results: Statistically significant dose related increase in all nuclear abnormalities was observed with micronuclea tion being the most reliable independent parameter for assessing radiation induced damage of cancer cells. Nuclear abnormalities were significantly higher in lesional tissue than normal but did not show statistically significant correlation with tumor response though there was a trend towards higher counts in patients with good tumor response. Conlusion: A direct dose-response relationship exists between the frequencies of various nuclear abnormalities and radiation exists in oral squamous cell carcinoma patients undergoing fractionated radiotherapy. Further studies are required to improve the understanding of the role of these changes in predicting tumor radiosensitivity.

Local Recurrence as Immunoglobulin G4 (IgG4)-Related Disease 10 Years after Radiotherapy to Ocular Adnexal Extranodal Marginal Zone B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue

In 2000, a 48-year-old woman developed a left orbital mass with lacrimal gland involvement and then, in 2003, a right orbital mass with lacrimal gland involvement, both of which were diagnosed as extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). She underwent 30 Gy external beam radiation to bilateral orbital lesions. The lymphoma cells in both lesions did not share the same clonality, as shown by amplification by polymerase chain reaction of the immunoglobulin heavy chain gene. Immunoglobulin light chain analysis by immunohistochemistry and messenger RNA in situ hybridization showed λ chain monotype in the left orbital lesion but κ chain monotype in the right orbital lesion. She developed recurrent left orbital mass with high uptake on fluorodeoxyglucose positron emission tomography fused with computed tomography in 2010, and excisional biopsy disclosed the formation of follicles and infiltration with immunoglobulin G4 (IgG4)-positive plasma cells mainly in interfollicular areas. The immunoglobulin light chain analysis showed the λ chain and κ chain bitype. With the immunohistopathological diagnosis of IgG4-related disease, the serum IgG4 level was found to show elevation at 376 mg/dL, and the patient chose observation. This is the first reported case of development of IgG4-related disease after bilataral orbital MALT lymphoma with external beam radiotherapy.

Stereotactic Body Radiotherapy as Boost for Organ-confined Prostate Cancer

Stereotactic body radiotherapy (SBRT) boost following external beam radiation therapy (EBRT) for advanced localized prostate cancer may reduce toxicity while escalating the dose. We present preliminary biochemical control and urinary, rectal and sexual toxicities for 73 patients treated with SBRT as a boost to EBRT. Forty-one intermediate- and 32 high-risk localized prostate cancer patients received 45 Gy EBRT with SBRT boost. Twenty-eight patients (38.3%) received a total SBRT boost dose of 18 Gy (3 fractions of 6 Gy), 28 patients (38.3%) received 19.5 Gy (3 fractions of 6.5 Gy), and 17 patients (23.2%) received 21 Gy (3 fractions of 7 Gy). Toxicity was assessed using the Radiation Therapy Oncology Group urinary and rectal toxicity scale. Biochemical failure was assessed using the Phoenix definition. The median follow-up was 33 months (range, 22 - 43 months). Less than 7% Grade II and no higher grade acute toxicities occurred. To date, one Grade III and no Grade IV late toxicities occurred. For the 97% of patients with 24 months minimum follow-up, 71.8% achieved a PSA nadir threshold of 0.5 ng/mL. Three intermediate-risk and seven high-risk biochemical failures occurred; one high-risk patient died of his cancer. Three-year actuarial biochemical control rates were 89.5% and 77.7% for intermediate- and high-risk patients, respectively. SBRT boost for prostate cancer treatment is safe and feasible with minimal acute toxicity. At 33 months late toxicity and biochemical control are promising. Long-term durability of these findings remains to be established.

Five-year Outcome of a Prospective Study Evaluating Tumor Bed Boost with Intra-operative Electron Irradiation (IOERT) in Breast Conserving Treatment for T1/T2 N0 Breast Cancer

Five-year Outcome of a Prospective Study Evaluating Tumor Bed Boost with Intra-operative Electron Irradiation (IOERT) in Breast Conserving Treatment for T1/T2 N0 Breast Cancer

Postoperative concurrent chemoradiotherapy for the high‐risk uterine cervical cancer

To determine whether concurrent chemoradiotherapy (CCRT) can improve the survival rate of high-risk uterine cervical cancer. We analyzed 16 cases of uterine cervical cancer that had undergone radical hysterectomy and pelvic lymphadenectomy from 2003 to 2008. The patients were eligible if they had histologically confirmed positive parametrial involvement, positive pelvic lymph nodes or non-squamous cell carcinoma. They received 50 Gy of external beam radiotherapy (RT) for the pelvis which was combined with chemotherapy. Cisplatin was administered intravenously every 3 weeks at a dose of 70 mg/m(2) during the RT. For renal function complication case, carboplatin was administered weekly. For control purposes, there were 14 cases treated in our hospital from 1995 to 2003 who had received only RT. We did not find any statistically significant difference in the disease-free survival rate between the CCRT group and the RT group. However, the overall survival rate was significantly higher for patients in the CCRT group compared with the RT group in positive lymph node cases and non-squamous cell carcinoma cases. Adverse effects were more frequent in the CCRT group. Over grade 3 toxicities were manifested as leukopenia, diarrhea and anemia. There was no local recurrence in CCRT group patients. CCRT seems to be beneficial for improving the survival rate of either positive lymph node or non-squamous cell carcinoma cases in high-risk uterine cervical cancer patients.