Day 1 :
Keynote Forum
Colin Paul Spears
California Northstate University College of Medicine, USA
Keynote: Standardized approach for comparison of therapeutic, mutagenic, and environmental alkylating agents in protic media
Time : 09:40-10:20

Biography:
Colin Paul Spears is a Medical Oncologist-Hematologist with a background in alkylating agent kinetics in collaboration with the late Prof George Olah who was awarded a Nobel Prize in Chemistry at the University of Southern California, where he pioneered nucleophilic selectivity assays. He was the Chair of the Cancer Center at Mercy General Hospital in Sacramento, California for 10 years, in private practice from 2006-2016, and is a Professor of Hematology at California Northstate University College of Medicine near Sacramento, California.
Abstract:
Introduction: The nitrobenzylpyridine (NBP) reagent has been used for over half a century as a screening nucleophile for detection and qualitative assessment of aliphatic nucleophilic substitution by primary and secondary alkyl substrates, therapeutic and mutagenic. These include all classical alkylating agents, ethyleneimines, alkyl sulfonates and sulfates, and alkyl halides and epoxides. The poor water solubility of NBP has prior been approached using non-protic binary reaction media and organic solvent extraction of quaternized-NBP product that is then alkalinized for chromophore absorbance measurement.
Methods: We developed a one-pot protic reaction media method for a truly quantitative, standardized method of alkylating activity measurement of a wide range of therapeutic and model mutagenic, and environmental moieties likely to be susceptible to aliphatic nucleophilic substitution, using 2% NBP in isopropanol (IPA), in 48% IPA-aqueous media with Tris-HCl pH 7 at 70oC, and in situ alkalinization with triethylamine (TEA). This approach was adapted for log[Ky/Knbp) values for NBP chromophore product competition with model nucleophiles, Y, for determination of Swain-Scott s-constants and nucleophilic selectivities by the Spears method. First-order half-lives of reaction of substrates with NBP and the extent of maximal alkylating activity were determined for all moieties. Values of log [Ko/Knbp] or n-constant intercepts were used to estimate rates of hydrolysis.
Results: Our approach capitalizes on the solubility of NBP in aqueous IPA, Tris HCl pH 7 at concentrations below reaction with alkyl substrates, and remarkable stabilities of alkyl-NBP products at prolonged incubation, with stable chromophore on in situ TEA alkalinization, and a lack of significant variation in extinction coefficient of alkyl-NBP products. We present results for a first time comparison of mono- vs. bis-functional substrates for alkylating activity among a broad range of therapeutic agents, and for comparison with model mutagens, and environmental moieties, which provide new insights into dosimetry and alkylating agent classification, and mechanistic considerations of nucleophilic substitution.
Keynote Forum
Juan Pablo Marquez Manriquez
Sonora Cancer Research Center (CICS), USA
Keynote: Targeting pancreatic ductal adenocarcinoma with multi-peptide immunotherapy and repurposing drugs
Time : 10:20-11:00

Biography:
Juan Pablo Marquez Manriquez, M.D. is a Medical Oncologist with training in Mexico, California and Seattle, Washington. His passion for Immunology and Oncology emerged from the very early stages of his life, as he prepared in pre-medicine by studying first Clinical Pharmacy and later medicine. He is currently developing projects for the prevention of gastrointestinal cancer in the CICS USA Seattle campus. He is currently specializing in the prevention of recurrence of tumors of high clinical impact such as ovarian, triple negative breast cancer, inflammatory breast cancer, colorectal and multiple myeloma. He worked as a medical doctor at the Tumor Vaccine Group of the University of Washington. Dr. Marquez Manriquez is Binational Medical Director of the Binational Alliance in Immuno-Oncology of Seattle & Sonora, including the Cancer Research Center in Sonora (CICS Sonora) both at the Ciudad Obregon Sonora campus and at the Seattle Washington campus (CICS USA), although his based in Seattle.
Abstract:
The immunology context, tumor stroma, active-antigen specific multi peptide immunotherapy and the use of repurposing drugs in pancreatic ductal adenocarcinoma (PDAC) clinically speaking are mainly unexplored. We first analyze retrospectively N=37 samples, median age= 47 yrs old from PDAC to study the adaptive and innate immune infiltration of CD8, Th1, Th2 and Tregs cells in tumor tissue and tumor stroma. We also evaluated by siRNA and systematic review 24 potential clinically relevant targets from biologically and clinically relevant proteins. Then we did in vitro using human PBMC’s and tumor cells lines according to systematic reviews of 20 cancer repurposing drugs to determine, if they were able to either improve granzyme B production and/or immunogenic cell death in order to validate what we found in the systematic reviews, Finally we predict from selected proteins 20 peptides in total as they were immunogenic by granzyme B ELISPOT and IgA + IgG + IgM antigen-specific ELISA. With this proof of principle, the local ethics committee approved the enrollment of eleven PDAC patients refractory but with a Karnofsky > 80% to be treated with this treatment approach. We found that peptides VCP 7 (P=0.001), fascin 8 (p=0.0001), FAP 2 (p=0.005), ALDH1 –B (p=0.002), Beclin-1 -E (P=0.01), IL-6R 4 (p=0.0001), NF-kB 5 (p=0.001), Muc-1 (0.001) and Alpha methylacyl-CoA racemase n (p.01) were the immunogenic according with prism and STAT3 analysis. Paladin and Galectin-3 were N.S. In these pilot trial eight peptides showed immunological correlation with a PFS (median=26 months). In terms of the drugs meloxicam (p=0001), enoxaparin (p=0001), clopidogrel (p=005), bortezomib (o.0001), naproxen (o.003), ursodeoxycholic acid (p=0.001 and thalidomide (p=0001) showed clinical activity in the combo therapy without significant adverse effects not even autoimmunity. As preliminary conclusion, the future in clinical oncology is rationally combine different therapies especially for challenge tumors such as PDAC and many others. Combining immuno treatment with validated repurposing drugs is a promising and safe approach. The next step is to publish this preliminary data and then a phase I clinical trial
Keynote Forum
Georgia Zhuo Chen
Emory University-School of Medicine, USA
Keynote: Optimization of EGFR-based targeted therapy and beyond
Time : 11:20-12:00

Biography:
Georgia Zhuo Chen is a Professor of Hematology and Medical Biology at Emory University. She has received several awards from the US National Institutes of Health (NIH) as a PI in the study of lung and head and neck cancers in the past years. She has generated more than 160 publications in peer-reviewed journals and serves as an Editorial Board Member for 5 journals. She has received the NIH Career Development Award in 1998 and an award as a Georgia Cancer Coalition Distinguished Cancer Scholar in 2006.
Abstract:
Cetuximab is a chimerized antibody against epidermal growth factor receptor (EGFR) and the only approved targeted agent for squamous cell carcinoma of the head and neck (SCCHN) in the US except newly developed immunotherapies. However, intrinsic and acquired resistance to EGFR targeted therapy inevitably occurs. Compensatory signaling from c-Met, HER3 and other (ErbB or HER) family members has been linked to the decreased sensitivity to EGFR-based therapy in SCCHN. We found that the expression of the HER3 activation ligand HRG1 is elevated in SCCHN compared to other solid tumors and HRG1 is an independent prognostic factor in SCCHN regardless of HPV status, suggesting a significant role of HER3 activation through HRG1 or its heterodimer partners (EGFR, HER2, and c-Met) in resistance to EGFR therapy. Simultaneously targeting c-Met and HER family members for treatments of the tumors resistant to EGFR-based therapy has shown better efficacies than any of the single targeting in animal models. In addition, accumulated evidence suggests that antibody dependent cellular cytotoxicity (ADCC) of cetuximab might result in upregulation of INFγ, while INFγ induces the expression of programmed death ligand-1 (PD-L1), an immune checkpoint receptor ligand, contributing to cetuximab resistance through an immune escape mechanism. We have recently demonstrated that the combination of cetuximab with a HER3 antibody down regulates PD-L1 more effectively than each antibody alone. It is expected therefore that elimination of intrinsic upregulation of PD-L1 using this combination may alter the T-cell profile in vivo.
Keynote Forum
Douglas E Gladstone
Johns Hopkins University, USA
Keynote: HLA donor specific antibodies and partially HLA-mismatched allogeneic HSCT

Biography:
Douglas E Gladstone is an Associate Professor in the Department of Oncology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. He is a Clinical Director of the Outpatient Bone Marrow Transplant Unit. In 2017, he led an educational program discussing how to lower donor specific antibodies to permissible levels for allogeneic bone marrow transplantation at the Annual American Society of Hematology conference.
Abstract:
Allogenic hematopoietic stem cell recipients may have preformed antibodies directed against foreign HLA antigens. The use of partially HLA-mismatched allogeneic hematopoietic stem cell donors allows for the possibility of the presence of circulating HLA donor-specific antibodies (DSAs) in the recipient. The presence of DSAs at the time of stem cell infusion increases the risk of primary graft failure. Recently developed technology using solid phase immunoassays (SPIs) with fluorochrome-conjugated beads has greatly improved the ability to detect and classify DSAs. When used in combination with the classic lymphocytotoxic complement-dependent and flow cytometric crossmatch tests, SPIs help provide DSA strength assessment. Both CD34+ cells and T-cells are required for donor engraftment, however the expression of HLA antibodies varies between these cells: all HLA loci are expressed on CD34+ cells (HLA-A highest, HLA- DQ lowest); HLA-A and B expression is higher on CD34+ cells than on T cells; HLA-C expression is lower on CD34+ than on T cells. Parous females frequently harbor DSAs. DSAs tend to be of higher intensity when directed against haploidentical first-degree relatives. DSA assessment requires frequent monitoring as their relative strength can change over time. Although the criteria that constitutes a prohibitive DSA is unknown, desensitization techniques can result in engraftment rates as experienced in fully HLA-matched allogeneic blood or marrow transplantation recipients.
- Organ Specific Cancer | Cancer Cell Biology | Cancer Drugs and Vaccines | Cancer Treatment
Location: Indianapolis
Chair
Guoxiong Xu
Jinshan Hospital of Fudan University, China
Co-Chair
Vincent Murray
University of New South Wales, Australia
Session Introduction
Leonel Alexander Rangel Reyna
Sonora Cancer Research Center (CICS), USA
Title: Antibodies titers against CMV putative predicts outcome in breast cancer patients
Biography:
Leonel Alexander Rangel Reyna has completed his education at La Salle University Victoria and training in General Hospital “Dr. Manuel Gea Gonzalez” in Mexico City. Currently, he is based in Ciudad Obregon, Sonora working on oncologic prevention with Binational Sonora Cancer Research Center (CICS) in Seattle/Sonora since 2016. He also works in the research area of the group identifying biologically and clinically relevant proteins for some neoplasia through immune assays as ELISA, ELISPOT, T-Cell Expansion, etc. Currently, he is in formation in the pathway to becoming a physician scientist to perform clinical relevant research in both pediatric and adult tumors, also he is involved in clinical oncology as attending physician.
Abstract:
Clinically speaking is mainly unknown the association of antibodies against Cytomegalovirus (CMV) and the prognosis in cancer patients. We studied (n=25) samples of breast cancer patients in different stages to address the possible link between high load viral titers using ELISA and we correlated with several clinical parameters including but not limited to OS, ECOG and stage. One of the possible pathways that the chronic presence of CMV in breast cancer patients can affect the outcome as potentially this type of virus may distract the immune system specially when the treatment is based with the combination of immunogenic chemotherapy, treat locally and systemically, multi-peptide active antigen specific immunotherapy and immunomodulation of cytokines. With this in mind we make a retrospective analysis identifying breast cancer patients (n=25), measuring the titers against CMV antigens and its relation with the mentioned clinical parameters. We found statistical significance in patients with high viral titles and OS. However, there is no pattern at this point with this preliminary data in all the studied cases, which may have to be related with the tumor microenvironment, breast cancer subtype and previous lines of ablative chemotherapy received as all of them where studied in refractory status as mentioned previously. This data could be useful to include for all cancer patients not just limited to breast cancer to include the titers of several viruses other than CMV such as EBV, HTLV-1/2, HCV, HBV and potentially some microbiota for instance Fusobacterium nucleatum. If we validate this data we will propose to include some broad spectrum antiviral agents in patients with potential clinical benefit.
Guoxiong Xu
Jinshan Hospital of Fudan University, China
Title: FLOT1 is a novel target of ovarian cancer for diagnosis and treatment
Biography:
Guoxiong Xu is a Professor of Oncology, Scientist and Director of Center Laboratory at Jinshan Hospital of Fudan University, China. He obtained his MD in the Faculty of Medicine at Shanghai Second Medical University in China; a Master degree in Medical and Pharmaceutical Research at the Free University of Brussels in Belgium and a PhD at York University in Canada. He has worked as a Clinician and Research Scientist at various universities and institutes. He has published more than 70 papers in peer-reviewed journals and has been serving as an Editorial Board Member of many scientific journals.
Abstract:
Ovarian cancer (OC) is the most lethal gynecological disease. Flotillin-1 (FLOT1) is a major protein of the component of lipid rafts involved in endocytosis, cell proliferation, cell adhesion, and receptor-mediated signal transduction. However, the role of FLOT1 in OC remains unknown. Current study defined FLOT1 as a novel serum biomarker of OC, improving the diagnostic sensitivity and accuracy, and to determine FLOT1 expression in human ovarian tumors and its effect on OC cell proliferation. FLOT1 protein expression was assessed in a tissue microarray by immunohistochemical staining. We found that most ovarian malignant and borderline tumors were FLOT1 protein positive, whereas ovarian benign tumors and normal tissues were negative. The staining of FLOT1 was stronger in serous malignant tumor and transitional cell carcinoma and weaker in mucinous tumor. The differentially expressed FLOT1 in freshly isolated serous tumors was confirmed by Western blotting. By analysis of histological types, we observed that FLOT1 protein expression was significantly associated with serous tumor. Silencing FLOT1 by FLOT1-siRNA inhibited OC cell proliferation and arrested the cell cycle at S phase. Inhibition of FLOT1 increased cyclin E1 protein expression. Overexpression of FLOT1 partially rescued the FLOT1-shRNA-suppressed cell proliferation. Furthermore, we found that the concentration of serum FLOT1, as well as CA125, was significantly increased in patients with OC measured by ELISA. The combination of FLOT1 and CA125 increased the detection rate and sensitivity of OC. Thus, we demonstrated that FLOT1 is highly expressed in ovarian malignant tumor and is secreted into the serum of patients with OC. The suppression of FLOT1 decreases OC cell proliferation. These data suggests that a novel diagnostic panel of FLOT1 and CA125 may be used as an optimal tool to improve the sensitivity and accuracy of OC diagnosis. Targeting FLOT1 may potentially have a clinical application in the treatment of OC.
Vincent Murray
University of New South Wales, Australia
Title: Genome-wide studies on the interaction of the anti-tumour drug Bleomycin (and analogues) at the transcription start sites of actively transcribed human genes
Biography:
Vincent Murray has been an Academic at the University of NSW since 1990. He has obtained his BSc (Hons) at Glasgow University, U K and his PhD at the National Institute for Medical Research, London, UK. He carried out Post-Doctoral Research at Princeton University, USA and at the Cancer Institute, Melbourne, Australia. He has been an active researcher in the field of molecular biology and cancer and his lab has concentrated on investigating the interaction of anti-tumor drugs with DNA. He has focused his research on several cancer chemotherapeutic agents including bleomycin, cisplatin and cisplatin analogues. Murray has published over 100 peer-reviewed papers.
Abstract:
Bleomycin is a glycopeptide that is utilized as a cancer chemotherapeutic agent to treat Hodgkin's lymphoma, squamous cell carcinoma and testicular cancer. It is thought that DNA damage is the main mechanism for the anti-tumor activity of bleomycin. In this study, next-generation DNA sequencing was utilized to investigate the effect of transcriptional activity on bleomycin cleavage. The main outcome of this study was that bleomycin preferentially cleaved at the transcription start sites (TSSs) of actively transcribed genes compared with non-transcribed genes in human cells. The enhanced bleomycin cleavage at TSSs correlated with the level of transcriptional activity. The pattern of bleomycin enhanced cleavage had peaks that were approximately 200 bp apart, and this indicated that bleomycin was identifying the presence of phased nucleosomes at TSSs. Hence bleomycin can be utilized to detect chromatin structures that are present at actively transcribed genes. The genome-wide cleavage of DNA by bleomycin analogues was also determined in human cells and it was ascertained that 6′-deoxy-BLM Z and ZBM preferentially cleaved at the transcription start sites of actively transcribed genes in human cells. The degree of preferential cleavage at the transcription start sites was quantified and an inverse correlation with the IC50 values was observed. This indicated that the degree of preferential cleavage at transcription start sites is an important component in determining the cytotoxicity of BLM analogues. This study provided insight into the mechanism of action of this anti-tumor drug where actively transcribed genes were preferentially targeted. This information could be used to enhance the cancer chemotherapeutic activity of bleomycin. For example, down-regulation of the highly expressed genes that are targeted by bleomycin could enhance the anti-tumor activity of bleomycin.
Itzia Xiuhnelly Nava Sanchez
Sonora Cancer Research Center (CICS), USA
Title: Kinetics of antibody-antigen binding evaluated by ELISA in refractory cancer patient
Biography:
Itzia Xiuhnelly Nava Sanchez is a Medical Doctor with training at La Salle University, Victoria and Escandon Hospital in Mexico City. Currently, she is a Medical Doctor and Investigator of the Binational Sonora Cancer Research Center (CICS) in Seattle/Sonora. She has also performed clinical experience, providing medical attention to patients who enter to cancer prevention protocol, carrying out clinical history, physical exploration, orientation about primary, secondary and tertiary prevention according to the age and comorbidities of patients, obtaining blood samples and subsequently analyzing the results. In the research area, she attends the development of scientific projects with clinic relevance and performed experiments focused on patient's immune response against cancer. She is a Member of ASCO and ESMO. She has been involved in some published scientific articles of the OMA/CICS group and aspires to subsequently specialize in the area of pediatric oncology.
Abstract:
Kinetics of antigen binding influence how, potently antibodies attack strong enough tumor cells at the clinical level and contribute in combination with other therapies potentially better outcomes when we induce multiple antigen specific antibodies against multiple clinical relevant targets in progressive and refractory cancer patients with an ECOG=0-1. The potential of immunological assays such as peptide Enzyme-Linked Immuno Sorbent Assay (ELISA) to predict affinity of antibody-antigen are mainly unexplored as many of the studies in cancer either for diagnosis, prognosis, etc. Most of the researchers assume that all the repertoire of antibodies, tumor associated antigens, recall antigens, etc. will behave equally. We decided to analyze by ELISA the kinetics of antigen-antibody binding at one, two, six, twelve, twenty four and seventy two hours without adding stopping solution. The study was retrospective and approved by the local ethic committee. We analyze (n=20) the kinetics of antibody-antigen reactions using clinically relevant immunogenic peptides such as RCAS1-A, VCP-4, SURVIVIN-A, Fascin-1, EGFR-D, Bcl2-A, SOX2-B and APE1-A in refractory cancer patients as following with breast cancer (n=2), pancreatic cancer (n=1), sarcoma (n=3), prostate cancer (n=2), ovarian cancer (n=1) and colorectal and colon cancer (n=1) and presumably healthy patients (n=10). With this proof of principle, the procedure was changed, adding the first antibody of each patient (serum dilution 1:200) and were incubated for 2 and 24 hours according with our preliminary results. We found statistical differences between different types of tumors, epitopes and two and twenty four hour’s kinetics. As preliminary conclusion, exposing the antigen-antibody interaction in two and twenty-four hours process in different subtypes of cancer, putatively predict the specific immune system behavior and the increase in titles in the reaction of an specific peptide at 24 hours might translate into greater maturity and memory of the immune system. However, an increased number of samples will be useful to clarify possible clinical associations.
Magda Mohamed Sultan
Medical Research Institute-Alexandria University, Egypt
Title: Variant morphology in multiple myeloma
Biography:
Magda Mohamed Sultan has completed her MD in Clinical Pathology and Laboratory Oncology in the National Cancer Institute at Cairo University in 1992. She was the Head of the Hematology Department of Medical Research Institute, Alexandria University, Egypt for eight years from 2007-2015. She is an Emeritus Professor in the institute, teaching for doctors and master degrees students and she is the Head of Hematology Department at Alborg Lab in Alexandria since 1996. She has published more than 25 papers and she is arbitrator for many thesis and many published papers.
Abstract:
Most plasma cell tumors are composed of easily recognizable plasma cells and can be diagnosed in tissue sections without any difficulty. Morphological analysis of bone marrow aspirate or trephine for the assessment of volume of plasma cell infiltrate remains a cornerstone in the diagnosis of multiple myeloma. In most cases the plasmacytic nature of the marrow infiltrate is readily apparent. However, some of these tumors may pose a considerable diagnostic problem as they may exhibit rare morphological variants, and unusual cytological and/or architectural features. Most of the morphological variants (including small cell, Mott Cell, multi-lobated, clear cell, pleomorphic and monocytoid ……..) have been documented in the literature but are not widely known amongst practicing hemato-pathologists. Awareness of these variants may help facilitate timely diagnosis. Hence, we provide a comprehensive review on this subject. And we are presenting some cases of multiple myeloma having variant morphology, as well as unusual architectural patterns admitted in our hematology department and diagnosed by bone marrow aspiration, bone marrow trephine biopsy and immuno phenotyping.
Sina Ghanean
Shahid Sadoughi University of Medical Sciences, Iran
Title: Oral squamous cell carcinoma: A diagnostic enigma
Biography:
Sina Ghanean has obtained his PhD in Oral and Maxillofacial Surgery at Shahid Sadoughi University of Medical Sciences, Yazd, Iran. He has published more than seven papers in reputed journals and presented more than eight abstracts at prestigious national and international conferences. He has also participated in writing/editing five books/chapters in the field of oral and maxillofacial surgery. Currently, his research interests are focused in discovering new methods for early diagnosis and treatment of squamous cell carcinoma
Abstract:
Squamous cell carcinoma (SCC) is considered one of the most prevalent malignancies affecting the oral cavity with broad spectrum of clinical appearances. SCC is considered as the sixth major cause of malignancy mortality worldwide and one of the ten most prevalent causes of death. Almost 500000 new cases occur each year worldwide. Oral squamous cell carcinoma (OSCC) is responsible for more than 90% of all oral malignancies. The most common sites of oral cavity involved are the tongue, followed by the floor of the mouth and buccal mucosa. Tobacco and alcohol are the two well acknowledged risk factors of OSCC. Clinical manifestations of SCC can actually be deceptive, such as an area of ulcerations or leucoplakic, granular or verruciform growth, all demonstrating possible surface changes, so they can easily be misdiagnosed as benign neoplasms or inflammatory lesions because of variable appearances. On the other hand, due to the proximity of the dentition, OSCC can be misdiagnosed at an early stage as a tooth-related inflammatory condition, such as periodontitis or an endodontic-related disease. Nevertheless, during histopathological assessment, problems may occur at all stages, from the processing of received tissues to the generation of the final report. These errors may occur due to inevitable limitations of histopathological diagnosis and staging; imprecision in histological detection and histological misapprehension. The aims of the presentation include: 1) to illustrate potential pitfalls and probable drawbacks and issues needing clarification in diagnosis process of OSCC 2) to draw attention to lesions mimicking OSCC and 3) to suggest, where achievable, practical solutions, progress and areas of further research to avoid misdiagnosis of OSCC.
Neeraj Jain
Sri Guru Ram Das University of Health Sciences And Research, India
Title: Stereotactic body radiotherapy in liver metastasis
Biography:
Neeraj Jain is an Associate Professor in Radiation Oncology at Sri Guru Ram Das University of Health Sciences, Amritsar. He is an Eminent Radiation Oncologist and participated in numerous national and international conferences and presented papers. He is the Vice Chairman of Indian College of Radiation Oncologists (ICRO). He is well versed in modern Radiotherapy techniques.
Abstract:
Stereotactic Body Radiation Therapy (SBRT) also known as stereotactic ablative Radiotherapy (SABR) is a newer modality of delivering radiation therapy for many primary and secondary tumors, with good results. Liver metastases from colorectal, breast and lung cancer are most common. Studies focusing on SBRT for liver metastases from a single primary tumor type colorectal cancer have been published. Regardless of age, patients should have good performance status (Eastern Cooperative Oncology Group 0-1 or Karnofsky >70), with absent or stable extra hepatic disease and adequate hepatic volume and function. Number of metastasis should be less than three and size less than 6 cm. Prescribed dose
is generally very high in range of 30 to 60 Gy in three fractions. The toxicity profile is generally low with a G3 toxicity rate of 1-10% and the incidence of Radiation Induced Liver disease less than 1%. The most common G2 toxicities included a transient hepatic enzyme levels increase over three months of SBRT and gastrointestinal, soft-tissue and bone complications, related to lesions close to the duodenum, bowel, skin and ribs. Duodenal ulceration and intestinal perforation is observed in patients with maximum doses greater than 30 Gy in three fractions to the duodenum and bowel. In few patients, non-traumatic rib fractures were experienced for maximum doses of 51.8 Gy and 66.2 Gy in six fractions to 0.5 cm3 of rib. Local control rates varied from 70% to 100% at one year and 60% to 90% at two years and correlated to lesion size <3 cm.