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Introduction and Purpose: With a significant global impact, treatment of gastrointestinal (GI) cancers still presents with challenges, despite current multimodality approaches in advanced stages. Clinical trials are expanding for checkpoint inhibition (ICI) combined with radiation therapy (RT). This review intends to offer a comprehensive image of the current data regarding the effectiveness of this association, and to reflect on possible directions to further optimize the results., Results: Several early phase studies demonstrated encouraging potential. However, translating preclinical outcomes to clinical settings proves challenging, especially in immunologically "cold" environments. GI cancers exhibit heterogeneity, requiring tailored approaches based on disease stage and patient characteristics. Current results, though promising, lack the power of evidence to influence the general practice., Conclusions: Finding biomarkers for identifying or converting resistant cancers is essential for maximizing responses, moreover in this context strategic RT parameters need to be carefully considered. Our review emphasizes the significance of having a thorough grasp of how immunology, tumour biology, and treatment settings interact in order to propose novel research avenues and efficient GI cancer therapy., Competing Interests: Declaration of Competing Interest No conflict of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Oncological outcomes are improving in gastrointestinal cancer with advancements in systemic therapies, and there is notable potential in combining immunotherapy and radiation therapy (RT) to allow for further improvements. Various preclinical and early phase II studies have shown promising synergy with immunotherapy and RT in gastrointestinal cancer. A few recent phase III studies have shown improved survival with the addition of immunotherapy to standard treatment for gastrointestinal cancer. The timing, duration, sequencing, and integration with other anti-cancer treatments are still areas of ongoing research. We have reviewed the published and ongoing studies of the combinations of immunotherapy and RT in gastrointestinal cancers.

Radiotherapy has become an indispensable and conventional means for patients with advanced solid tumors including gastrointestinal cancer. However, innate or acquired radiotherapy resistance remains a significant challenge and greatly limits the therapeutic effect, which results in cancer relapse and poor prognosis. Therefore, it is an urgent need to identify novel biomarkers and therapeutic targets for clarify the biological characteristics and mechanism of radiotherapy resistance. Recently, lots of studies have revealed that non-coding RNAs (ncRNAs) are the potential indicators and regulators of radiotherapy resistance via the mediation of various targets/pathways in different cancers. These findings may serve as a potential therapeutic strategy to overcome radiotherapy resistance. In this review, we will shed light on the recent findings regarding the functions and regulatory mechanisms of ncRNAs following radiotherapy, and comprehensively discuss their potential as biomarkers and therapeutic targets in radiotherapy resistance of gastrointestinal cancer., Competing Interests: Conflict of interest statement The authors declare that they have no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Purpose: Beam gating with deep inspiration breath hold (DIBH) usually depends on some external surrogate to infer internal target movement, and the exact internal movement is unknown. In this study, we tracked internal targets and characterized residual motion during DIBH treatment, guided by a surface imaging system, for gastrointestinal cancer. We also report statistics on treatment time., Methods and Materials: We included 14 gastrointestinal cancer patients treated with surface imaging-guided DIBH volumetrically modulated arc therapy, each with at least one radiopaque marker implanted near or within the target. They were treated in 25, 15, or 10 fractions. Thirteen patients received treatment for pancreatic cancer, and one underwent separate treatments for two liver metastases. The surface imaging system monitored a three-dimensional surface with ± 3 mm translation and ± 3° rotation threshold. During delivery, a kilovolt image was automatically taken every 20° or 40° gantry rotation, and the internal marker was identified from the image. The displacement and residual motion of the markers were calculated. To analyze the treatment efficiency, the treatment time of each fraction was obtained from the imaging and treatment timestamps in the record and verify system., Results: Although the external surface was monitored and limited to ± 3 mm and ± 3°, significant residual internal target movement was observed in some patients. The range of residual motion was 3-21 mm. The average displacement for this cohort was 0-3 mm. In 19% of the analyzed images, the magnitude of the instantaneous displacement was > 5 mm. The mean treatment time was 17 min with a standard deviation of 4 min., Conclusions: Precaution is needed when applying surface image guidance for gastrointestinal cancer treatment. Using it as a solo DIBH technique is discouraged when the correlation between internal anatomy and patient surface is limited. Real-time radiographic verification is critical for safe treatments., (© 2022 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

Magnetic resonance imaging (MRI) has a key role to play at multiple steps of the radiotherapy (RT) treatment planning and delivery process. Development of high-precision RT techniques such as intensity-modulated RT, stereotactic ablative RT, and particle beam therapy has enabled oncologists to escalate RT dose to the target while restricting doses to organs at risk (OAR). MRI plays a critical role in target volume delineation in various disease sites, thus ensuring that these high-precision techniques can be safely implemented. Accurate identification of gross disease has also enabled selective dose escalation as a means to widen the therapeutic index. Morphological and functional MRI sequences have also facilitated an understanding of temporal changes in target volumes and OAR during a course of RT, allowing for midtreatment volumetric and biological adaptation. The latest advancement in linear accelerator technology has led to the incorporation of an MRI scanner in the treatment unit. MRI-guided RT provides the opportunity for MRI-only workflow along with online adaptation for either target or OAR or both. MRI plays a key role in post-treatment response evaluation and is an important tool for guiding decision making. In this review, we briefly discuss the RT-related applications of MRI in the management of brain, prostate, and GI malignancies., Competing Interests: Shashank SrinivasanEmployment: GlaxoSmithKlineNo other potential conflicts of interest were reported.

Background: Image-guided radiotherapy (IGRT) has significantly improved the precision in which radiotherapy is delivered in cancer treatment. Typically, IGRT uses bony landmarks and key anatomical structures to locate the tumor. Recent studies have demonstrated the feasibility of peri-tumor fiducials in enabling even more accurate delineation of target and normal tissue. The use of gold coils as fiducials in gastrointestinal tumors has been extensively studied. However, placement requires expertise and specialized endoscopic ultrasound equipment. This article reports the long-term outcomes of using a standard gastroscopy to inject liquid fiducials for the treatment of oesophageal and gastric tumors with IGRT., Aim: To assess the long-term outcomes of liquid fiducial-guided IGRT in a cohort of oesophageal and gastric cancer patients., Methods: A retrospective cohort study of consecutive adults with Oesophagogastric cancers referred for liquid fiducial placement before definitive/neo-adjuvant or palliative IGRT between 2013 and 2021 at a tertiary hospital in Melbourne, Australia was conducted. Up to four liquid fiducials were inserted per patient, each injection consisting of 0.2-0.5mL of a 1:1 mixture of iodized oil (Lipiodol; Aspen Pharmacare) and n-butyl 2-cyanoacrylate (Histoacryl ® ; B. Braun). A 23-gauge injector (Cook Medical) was used for the injection. All procedures were performed by or under the supervision of a gastroenterologist. Liquid fiducial-based IGRT (LF-IGRT) consisted of computer-assisted direct matching of the fiducial region on cone-beam computerised tomography at the time of radiotherapy. Patients received standard-IGRT (S-IGRT) if fiducial visibility was insufficient, consisting of bone match as a surrogate for tumor position. Radiotherapy was delivered to 54Gy in 30 fractions for curative patients and up to 45Gy in 15 fractions for palliative treatments., Results: 52 patients were referred for liquid fiducial placement within the study period. A total of 51 patients underwent liquid fiducial implantation. Of these a total of 31 patients received radiotherapy. Among these, the median age was 77.4 years with a range between 57.5 and 88.8, and 64.5% were male. Twenty-seven out of the 31 patients were able to have LF-IGRT while four had S-IGRT. There were no complications after endoscopic implantation of liquid fiducials in our cohort. The cohort overall survival (OS) post-radiotherapy was 19 mo (range 0 to 87 mo). Whilst the progression-free survival (PFS) post-radiotherapy was 13 mo (range 0 to 74 mo). For those treated with curative intent, the median OS was 22.0 mo (range 0 to 87 mo) with a PFS median of 14.0 mo (range 0 to 74 mo). Grade 3 complication rate post-radiotherapy was 29%., Conclusion: LF-IGRT is feasible in 87.1% of patients undergoing liquid fiducial placement through standard gastroscopy injection technique. Our cohort has an overall survival of 19 mo and PFS of 13 mo. Further studies are warranted to determine the long-term outcomes of liquid-fiducial based IGRT., Competing Interests: Conflict-of-interest statement: Dr. BE on behalf of all authors has nothing to disclose., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: This communication reports the identification of a new panel of transcriptional changes in inflammation-associated genes observed in response to ionising radiation received by radiotherapy patients., Methods: Peripheral blood samples were taken with ethical approval and informed consent from a total of 20 patients undergoing external beam radiotherapy for breast, lung, gastrointestinal or genitourinary tumours. Nanostring nCounter analysis of transcriptional changes was carried out in samples prior and 24 h post-delivery of the 1st radiotherapy fraction, just prior to the 5th or 6th fraction, and just before the last fraction., Results: Statistical analysis with BRB-ArrayTools, GLM MANOVA and nSolver, revealed a radiation responsive panel of genes which varied by patient group (type of cancer) and with time since exposure (as an analogue for dose received), which may be useful as a biomarker of radiation response., Conclusion: Further validation in a wider group of patients is ongoing, together with work towards a full understanding of patient specific responses in support of personalised approaches to radiation medicine.

Radiotherapy remains one of the contemporary cornerstones of cancer treatment in the neoadjuvant, curative, adjuvant and palliative settings, either in isolation or as a multimodal approach. Moreover, recent advances in targeted immune checkpoint therapy have firmly established immunotherapy as the fourth pillar in cancer therapy alongside surgery, chemotherapy and notably radiotherapy. There is emerging evidence to suggest both radioresistance and reduced efficacy of immune checkpoint blockade (ICB) are potentiated by the tumour microenvironment (TME) and in fact modulating aspects of this immunosuppressive milieu is instrumental to unlocking anti-tumour immunity. The response rates of Upper Gastrointestinal (UGI) malignancies to ICB remains modest at 10-15%, compared to melanoma at 20-40%. Harnessing the effects of radiotherapy through remodelling of the TME using ICB as a radiosensitisor is an avenue showing promise. Here we explore the rationale behind combining radiotherapy with ICB, as a symbiotic relationship in shifting the balance in favour of anti-tumour immunity. We discuss the effects of radiotherapy on immunogenic cell death, the concept of the abscopal effect, the importance of the cGAS STING pathway, and their relevance in the context of the tumour microenvironment. Furthermore, dosing and timing of radiotherapy and ICB is now being evaluated for its synergistic effects on host tumour immunity, and we review the ongoing efforts and current available literature for single agent and dual agent ICB in combination multimodal therapy for both locally advanced operable and metastatic disease of the upper gastrointestinal tract.

Background/aim: To assess predictors of local control (LC) for stereotactic ablative radiotherapy (SAbR) in pulmonary oligometastatic disease (OMD) from gastrointestinal (GI) malignancies., Patients and Methods: Patients with pulmonary OMD treated with SAbR from January 2016 to December 2018 were included in this observational analysis. Primary endpoint was LC. Uni- and multivariate analyses to assess variable correlations were conducted., Results: Thirty-seven patients and 59 lung metastases were evaluated. The delivered dose was 30-60 Gy in 3-8 fractions. After a median follow-up of 23.0 months (range=6.3-50.4 months), LC rate at 1/2 years was 89.7%/85.0%, and increased to 96.0%/91.0% for lesions treated with a biologically effective dose (BED 10 ) ≥100 Gy (p=0.03). RECIST response at 6 months was predictive for LC (p=0.002)., Conclusion: SAbR is an effective option for pulmonary OMD from GI malignancies. A BED 10 ≥100 Gy and radiological response at 6 months can affect LC., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Early-stage primary gastrointestinal (GI) low-grade B-cell lymphoma shows good therapeutic response to primary radiotherapy. However, there is no clear guideline for the evaluation of response to radiation therapy currently. The aim of this study was to analyze the relationship between the best response time and the clinical course after radiotherapy., Methods: Patients who underwent radiotherapy for treatment of primary GI low-grade B-cell lymphoma from September 2007 to December 2018 at Seoul St. Mary's Hospital were included. Early responders were defined by best response within 6 months after radiotherapy, and delayed responders after 6 months. Clinical and pathological factors associated with delayed response and survival analyses were performed to investigate the recurrence and survival during follow-up., Results: A total of 43 patients were evaluated and the number of gastric mucosa-associated lymphoid tissue and duodenal follicular lymphoma was 36 and 7, respectively. All of 43 patients showed complete remission to radiotherapy and the best response time after radiotherapy was a median of 3 months. There were 8 delayed responders with a median duration of 8.9 months. Early and delayed responders were characterized by a significant difference in depth of invasion beyond the mucosal layer., Conclusions: Delayed responders did not show differences in oncological outcomes compared with early responders. They were allowed to watch and wait for an additional 6 to 12 months without further treatment.

Introduction: Cancer in elderly patients represents a global health challenge due to the increase in its incidence and its associated mortality. In our country it is the second leading cause of death in people over 65 years. In the coming years, the problem will increase, with a prognosis of people over 65 years of 35% in 2050. Radiotherapy is an essential part of the multidisciplinary treatment of cancer in elderly patients, where sometimes it is considered as the first therapeutic option and others, as an alternative to surgery and/or chemotherapy if they pose too much risk. The technological development of Radiation Oncology in recent years has allowed optimizing treatments and reducing side effects in elderly patients, who tend to have a higher incidence of comorbidities. It is essential that professionals involved in the multidisciplinary treatment of cancer know the possible toxicity and its management in oncogeriatric patients; otherwise, the percentage of patients who do not receive radiotherapy despite of an adequate indication will not decrease. In this sense, it is necessary to recognize those patients who may suffer from malnutrition or are at risk of suffering it, to initiate a nutritional intervention that minimizes weight loss that alters or even causes the suspension of the planned treatment.

Purpose: The purpose of this study was to validate a new prognostic model (GI-GPA) originally derived from a multi-center database (USA, Canada, Japan)., Patients and Methods: This retrospective study included 92 German and Norwegian patients treated with individualized approaches, always including brain radiotherapy. Information about age, extracranial spread, number of brain metastases, performance status and other variables was collected. The GI-GPA score was calculated as described by Sperduto et al. RESULTS: Median survival was 4 months. The corresponding figures for the 4 different prognostic strata were 2.3, 4.4, 9.4 and 12.7 months, respectively (p = 0.0001). Patients whose management included surgical resection had longer median survival than those who were treated with other approaches (median 11.9 versus 3.0 months, p = 0.002). Comparable results were seen for additional systemic therapy (median 8.5 versus 3.5 months, p = 0.01)., Conclusion: These results confirm the validity of the GI-GPA in an independent dataset from a different geographical region, despite the fact that overall survival was shorter in all prognostic strata, compared to Sperduto et al. Potential explanations include differences in molecular tumor characteristics and treatment selection, both brain metastases-directed and extracranially. Long-term survival beyond 5 years is possible in a small minority of patients.

The 20th annual Western Canadian Gastrointestinal Cancer Consensus Conference was held in Saskatoon, Saskatchewan, 28-29 September 2018. This interactive multidisciplinary conference is attended by health care professionals from across Western Canada (British Columbia, Alberta, Saskatchewan, and Manitoba) who are involved in the care of patients with gastrointestinal cancers. In addition, invited speakers from other provinces participate. Surgical, medical, and radiation oncologists, and allied health care professionals participated in presentations and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses current issues in the management of colorectal cancers., Competing Interests: CONFLICT OF INTEREST DISCLOSURES We have read and understood Current Oncology’s policy on disclosing conflicts of interest, and we declare that we have none., (2019 Multimed Inc.)

Background: Intracranial metastasis of Gastrointestinal Stromal Tumors (GISTs) is rare but presents unique treatment challenges. We present a case of intracranial metastasis of GIST with a systematic review of the literature. A literature search using key terms "'gastrointestinal stromal tumor' AND brain AND metastasis"" was conducted through May 2019 via Embase and Pubmed according to PRISMA guidelines. Only cases describing intradural metastases rather than calvarial or intraorbital metastases were included., Case Presentation: A 57-year-old woman with history of GIST metastatic to the liver presented with a six-week history of left facial weakness, left hearing loss, and left facial numbness, and a one-week history of headaches, gait disturbance, and dizziness. MRI revealed a contrast-enhancing dural-based left middle cranial fossa mass measuring 2.9 cm × 3.1 cm × 3.4 cm with extension into the internal auditory canal and cerebral edema. A left temporal craniotomy was performed to excise the lesion, and the patient was discharged to a rehabilitation facility at her preoperative baseline. Intraoperative pathology revealed a spindle cell neoplasm, postoperative MRI demonstrated gross total resection of the lesion, and microscopic analysis demonstrated sheets of spindled tumor cells with short ovoid, irregular, hyperchromatic nuclei and scattered large atypical nuclei without extensive necrosis. Immunohistochemical staining was positive for KIT proto-oncogene (CD117, c-KIT), and the patient was put on imatinib (400 mg/day)., Conclusions: Of the 18 cases analyzed and our present case, metastasis typically involved the cerebrum with only one in infratentorial elements. The tumors in seven of the cases involved the dura, and one case metastasized to the pituitary. Eight patients died following treatment. Surgery remains the mainstay of intracranial metastatic GIST, however there are many reports of good responses to radiation or chemotherapy alone. More investigation is required to determine the best treatment course for these patients.

Background: We sought to determine the role of abdominal reirradiation for patients presenting with recurrent or new primary gastrointestinal (GI) malignancies. At our institution, we have established a hyperfractionated, accelerated reirradiation regimen consisting of 39 Gray (Gy) in 26 twice-daily fractions. Although this regimen is used frequently in the pelvis, we sought to determine its toxicity and efficacy for abdominal tumors., Methods: Twenty-four patients who received abdominal reirradiation with a hyperfractionated, accelerated approach from 2000 to 2017 were identified. Overall survival (OS) and local progression-free survival (LPFS) were calculated using the Kaplan-Meier method. Several patient, tumor and treatment characteristics were evaluated on univariate analyses for association with OS and LPFS using a Cox proportional hazards model., Results: Of the twenty-four patients identified, the majority (n = 11, 46%) had pancreatic adenocarcinoma as their primary disease but also included upper GI adenocarcinoma (n = 4), colon adenocarcinoma (n = 3), hepatobiliary cancers (n = 4) and other malignancies (n = 2). The majority of patients received 45-50.4Gy in 1.8Gy fractions as their initial abdominal radiation course. The median reirradiation dose was 39Gy in 26 twice-daily fractions with a minimum six hour interval. The median [interquartile range (IQR)] interval between the courses of radiotherapy was 28 [18.6-38.9] months. Only palliative reirradiation intent was associated with decreased OS. While colon adenocarcinoma primary was significantly associated with increased LPFS, the sample size was small (n = 3). The 1-yr rate of LPFS was 38%. The median [IQR] duration of freedom from local progression was 8 [3.8-19.2] months. The 1-year OS was 50% and the median (IQR) OS was 14 [6.3-19.6] months. Thirteen patients (54%) had acute side effects with one patient experiencing G3 nausea and one experiencing a G4 bleed; the remaining patients experienced G1-G2 symptoms., Conclusion: Hyperfractionated, accelerated reirradiation to the abdomen was relatively well-tolerated but provided limited local control to recurrent or second primary abdominal malignancies. Reirradiation could play a role in treating these patients with palliative or curative intent, but alternative strategies for delivering increased biologically effective dose should be further explored.

As we mark 150 years since the birth of Marie Curie, we reflect on the global advances made in radiation oncology and the current status of radiation therapy (RT) research. Large-scale international RT clinical trials have been fundamental in driving evidence-based change and have served to improve cancer management and to reduce side effects. Radiation therapy trials have also improved practice by increasing quality assurance and consistency in treatment protocols across multiple centres. This review summarises some of the key RT practice-changing clinical trials over the last two decades, in four common cancer sites for which RT is a crucial component of curative treatment: breast, lung, urological and lower gastro-intestinal cancer. We highlight the global inequality in access to RT, and the work of international organisations, such as the International Atomic Energy Agency (IAEA), the European SocieTy for Radiotherapy and Oncology (ESTRO), and the United Kingdom National Cancer Research Institute Clinical and Translational Radiotherapy Research Working Group (CTRad), that aim to improve access to RT and facilitate radiation research. We discuss some emerging RT technologies including proton beam therapy and magnetic resonance linear accelerators and predict likely future directions in clinical RT research.

The level of oxidative stress is important in the initiation and progression of various age-related diseases, such as cancer. The level of oxidative stress may also play a significant role in cancer patients' response to treatment. We aimed to investigate whether serum 8-oxo-dG as a marker of oxidative stress is a predictor of tumour response. We used modified ELISA with a two-step filtration to analyse 8-oxo-dG in serum. The relationship between 8-oxo-dG levels, tumour response, and toxicity was studied in 19 oesophageal cancer patients who received radiotherapy and 16 gastric cancer patients who received chemotherapy. In the radiotherapy and the merged radio- and chemotherapy groups, the baseline levels of 8-oxo-dG were significantly lower in responder patients than in nonresponder patients and the increments after treatment were greater. In comparison with patients whose serum 8-oxo-dG levels decrease after treatment, patients with increasing levels had a longer median "progression-free survival." Our results, although preliminary, suggest that serum levels of 8-oxo-dG may potentially be used to predict the sensitivity and outcome of radiotherapy and chemotherapy of upper gastrointestinal tumours. Patients with 8-oxo-dG levels that are low prior to treatment and subsequently increase after treatment may be more likely to benefit from the therapy.

Objective: Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors of the gastrointestinal tract, which frequently cause intraabdominal metastases. The current standard of care is surgery for localized cases, and adjuvant imatinib is recommended for tumors with a high risk of recurrence. To date, radiotherapy has not been commonly accepted as a part of multimodality treatment approach other than palliation. However, recently published case reports and some small series suggest that radiotherapy is a valuable option for controlling locally progressive, drug-resistant disease. The aim of this review is to provide a viewpoint from a radiation oncologist concerning the management of GISTs, especially rectal GIST, and clarify the role and technical aspects of radiotherapy in the treatment approach., Data Sources: A comprehensive search in PubMed using the keywords "radiotherapy for rectal GIST" and "rectal GIST" was undertaken. The literature search included the related articles after 1995., Study Selection: The main articles including rectal GIST case reports and GIST series containing rectal cases were the primary references., Results: Surgery is the mainstay of treatment. However, to date, radiotherapy is included in the multidisciplinary treatment strategy of rectal GISTs in some circumstances with palliative, adjuvant, or definitive intent using different treatment doses and fields., Conclusions: Recently reported long-term local control rates indicate that GIST is a radiosensitive disease. This makes radiotherapy a valuable alternative in GIST management with curative intent, especially in patients who (1) cannot tolerate or are resistant to chemotherapy agents, (2) have an unresectable disease, (3) have a gross or microscopic residual disease after surgery, and (4) have a recurrent disease.

Upper gastrointestinal cancers are common and account for a high proportion of cases of cancer-related morbidity and mortality. Combined-modality therapy with surgery, chemotherapy, and radiation therapy is standard treatment for esophageal and gastroesophageal junction cancers. For gastric cancer, the need to include radiation therapy appears to depend on the quality of the surgery performed. Radiation therapy plays an uncertain role in the surgical management of pancreatic cancer, and the results of ongoing clinical trials are awaited. Retrospective studies support the inclusion of radiotherapy in the surgical management of biliary tract cancers. The development of more effective systemic therapy for upper gastrointestinal cancers may ultimately lead to a greater survival benefit due to the potential for improved local tumor control achieved with radiotherapy.

Background: Brain metastases of gastrointestinal origin are a rare occurrence. Radiation therapy (RT) in the form of stereotactic radiosurgery (SRS) or whole brain radiation therapy (WBRT) is an effective established treatment modality in either the definitive or adjuvant setting. The aim of this study is to assess the long-term clinical outcomes of patients with gastrointestinal (GI) brain metastases treated with SRS or WBRT., Methods: In this single institutional retrospective review, we detail the outcomes of patients diagnosed with metastatic brain tumors from an adenocarcinoma gastrointestinal primary. Patients were treated using stereotactic radiosurgery or whole brain radiation therapy. Initial site control (defined as lesions visualized on imaging at time of treatment), new site control (defined as new intracranial lesions visualized on follow-up imaging), and overall survival were calculated using the Kaplan-Meier method., Results: Thirty-three patients were treated from August 2008 to December 2015. Primary malignancy locations were as follows: 18 colon, 6 esophagus, 4 rectum, 5 other. Median total dose delivered was 25 Gy (18-35 Gy) in a median of 4 fractions for SRS and 30 Gy (10.8-40 Gy) in 10 fractions for WBRT. Crude initial site control at last radiographic follow-up was 64.3% after SRS and 41.7% after WBRT. Eleven of the 28 brain lesions (39.3%) treated with SRS had resection of the SRS-treated lesion prior to radiation therapy. Five of the twelve patients (41.7%) undergoing WBRT underwent cranial resection prior to radiation therapy. Crude new site control at last radiographic follow-up was 46.4% after SRS and 83.3% after WBRT. Kaplan-Meier analysis of overall survival did not show any statistically significant difference between WBRT and SRS (p = 0.424). Median overall survival for SRS patients was 5.2 months (0.5-57.5) and for WBRT patients 4.4 months (0-15). Kaplan-Meier analysis of new site control was significantly improved with WBRT versus SRS (p = 0.017). Total dose, treatment with WBRT, and active extracranial disease were statistically significant on multivariate analysis for new site control (p < 0.05)., Conclusions: Survival and intracranial disease control are poor following RT for brain metastases from GI primaries. In this small series, outcomes are worse than published series for other primary malignancies metastatic to the brain and further research into methods of local control improvement is warranted. Future studies should explore the utility of dose escalation or radiosensitization in this patient population.

Radiation is an important treatment modality for gastrointestinal tumors, but intestinal injury is a common side effect. Here we describe a physiologically relevant model for studying the molecular determinants of radiation-induced intestinal damage and testing novel radioprotectors. The model employs a radiopaque marker implanted into the surface of the mouse jejunum, serving as a fiducial marker for precise radiation targeting. Mice were imaged with Cone-Beam CT (CBCT) and irradiated (IR) to the marked area using the Small Animal Radiation Research Platform (SARRP). IR-induced damage was acute but reversible and largely restricted to the area of the marker, leaving the surrounding tissues intact. Although whole gut irradiation with these doses caused lethal GI syndrome, focal (5 mm) radiation of the intestine did not cause any weight loss or lethality. However, fibrosis and collagen deposition 4 months post-IR indicated chronic intestinal damage. A separate cohort of mice was treated daily with curcumin, a clinically tested radioprotector, prior to and post-IR. Curcumin-treated mice showed significant decreases in both local and systemic inflammatory cytokine levels and in fibrosis, suggesting it is an effective radioprotector of the intestine. Our results indicate that this model, which emulates clinically relevant intestinal radiation-induced injury, can be used to assess radioprotectors prior to testing in the clinic. Cancer Res; 77(4); 908-17. ©2016 AACR ., (©2016 American Association for Cancer Research.)

We investigate the difference between surface matching and target matching for pelvic radiation image guidance. The uniqueness of our study is that all patients have multiple CT-on-rails (CTOR) scans to compare to corresponding AlignRT images. Ten patients receiving pelvic radiation were enrolled in this study. Two simulation CT scans were performed in supine and prone positions for each patient. Body surface contours were generated in treatment planning system and exported to AlignRT to serve as reference images. During treatment day, the patient was aligned to treatment isocenter with room lasers, and then scanned with both CTOR and AlignRT. Image-guidance shifts were calculated for both modalities by com-parison to the simulation CT and the differences between them were analyzed for both supine and prone positions, respectively. These procedures were performed for each patient once per week for five weeks. The difference of patient displace-ment between AlignRT and CTOR was analyzed. For supine position, five patients had an average difference of displacement between AlignRT and CTOR along any direction (vertical, longitudinal, and lateral) greater than 0.5 cm, and one patient greater than 1 cm. Four patients had a maximum difference greater than 1 cm. For prone position, seven patients had an average difference greater than 0.5 cm, and three patients greater than 1 cm. Nine patients had a maximum difference greater than 1 cm. The difference of displacement between AlignRT and CTOR was greater for the prone position than for the supine position. For the patients studied here, surface matching does not appear to be an advisable image-guidance approach for pelvic radiation therapy for patients with either supine or prone position. There appears to be a potential for large alignment discrepancies (up to 2.25 cm) between surface matching and target matching.

Background: Palliative radiotherapy (PRT) can significantly improve quality of life for patients dying of cancer with bone metastases. However, an aggressive cancer treatment near end of life is an indicator of poor-quality care. But the optimal rate of overall palliative RT use near the end of life is still unknown. We sought to determine the patterns of palliative radiation therapy (RT) utilization in patients with bone metastases towards their end of life in a population-based, publicly funded health care system., Methods: All consecutive patients with bone metastases treated with RT between 2007 and 2011 were identified in a provincial Canadian cancer registry database. Patients were categorized as receiving RT in the last 2 weeks, 2-4 weeks, or >4 weeks before their death. Associations between RT fractionation utilization by these categories, and patient and provider characteristics were assessed through logistic regression., Results: Of the 16,898 courses 1734 (10.3) and 709 (4.2%) were prescribed to patients in the last 2-4 weeks and <2 weeks of their life, respectively. Primary lung (8%) and gastrointestinal (6.9%) cancers received palliative RT more commonly in the last 2 weeks of life (OR 3.72 [2.86-4.84] & 3.33 [2.42-4.58] respectively, p <0.001). Among the 709 patients who received RT in the last 2 weeks of life, 350 (49), 167 (24), and 127 (18%) were for spine, pelvis, and extremity metastases, respectively. RT was prescribed most frequently to spine (5%) and extremity (4%) metastases p <0.001 in the last two weeks of life, though only varied between 1% (sternum) and 5% (spine) by site of metastases. Single fraction RT was prescribed more commonly in the last 2 weeks of life (64.2%), compared to individuals who received RT 2-4 weeks (54.5), and >4 weeks (47.9%) before death (p <0.001)., Conclusions: This population-based analysis found that only 4% of patients with bone metastases received radiation therapy during the last 2 weeks of their life in our population-based, publicly funded program, though it was significantly higher in patients with lung cancer and those with metastases to the spine or extremity. Appropriately, use of multiple fractions palliative RT was less common in patients closer to death.

The aim of this research is to determine the characteristics of endothelial factors and the hemostatic system conditions with malignant neoplasms patients, which were exposed to ionizing radiation. Total number of examined people is 223, 153 of them are patients with gastrointestinal tract oncopathology. The article presents the results of the analysis of numerical indicators of endothelial condition and platelet hemostasis of patients, who had cancer. They lived in the regions of Kazakhstan, subjected to contamination of radionuclides as a result of nuclear weapons tests, which took place in this region from 1949 to 1989. These results then were compared to cancer patients and healthy individuals with no radiation risk. The study revealed the presence of higher levels of endothelial dysfunction and following trigger of the hemostatic system in patients with malignant tumors of the gastrointestinal tract. In particular, the defined high degree of endothelial dysfunction include endothelium- dependent vasodilation, content desquamated endothelial cells in peripheral blood and von Willebrand factor. These indicators have a clear correlation with the degree of disorder of studied parameters of the hemostasis, which can cause the development of thrombotic complications.

Background: The kidneys are a principal dose-limiting organ in radiotherapy for upper abdominal cancers. The current understanding of kidney radiation dose response is rudimentary. More precise dose-volume response models that allow direct correlation of delivered radiation dose with spatio-temporal changes in kidney function may improve radiotherapy treatment planning for upper-abdominal tumours., Methods/design: The Radiotherapy of Abdomen with Precise Renal Assessment with SPECT/CT Imaging (RAPRASI) is an observational clinical research study with participating sites at Sir Charles Gairdner Hospital (SCGH) in Perth, Australia and the Peter MacCallum Cancer Centre (PMCC) in Melbourne, Australia. Eligible patients are those with upper gastrointestinal cancer, without metastatic disease, undergoing conformal radiotherapy that will involve incidental radiation to one or both kidneys. For each patient, total kidney function is being assessed before commencement of radiotherapy treatment and then at 4, 12, 26, 52 and 78 weeks after the first radiotherapy fraction, using two procedures: a Glomerular Filtration Rate (GFR) measurement using the 51Cr-ethylenediamine tetra-acetic acid (EDTA) clearance; and a regional kidney perfusion measurement assessing renal uptake of 99mTc-dimercaptosuccinic acid (DMSA), imaged with a Single Photon Emission Computed Tomography / Computed Tomography (SPECT/CT) system. The CT component of the SPECT/CT provides the anatomical reference of the kidney's position. The data is intended to reveal changes in regional kidney function over the study period after the radiotherapy. These SPECT/CT scans, co-registered with the radiotherapy treatment plan, will provide spatial correlation between the radiation dose and regional renal function as assessed by SPECT/CT. From this correlation, renal response patterns will likely be identified with the purpose of developing a predictive model., Trial Registration: Australian New Zealand Clinical Trials Registry: ACTRN12609000322235.

Background: Due to low tolerance to chemotherapy, the maximum number of cycles of postoperative adjuvant chemotherapy is 4 in adjuvant gastric clinical trials. The aim of this study is to retrospectively evaluate the safety and efficacy of adjuvant epirubicin-based triplet chemotherapy and radiotherapy in the treatment of resected locally advanced stomach or gastroesophageal junction adenocarcinoma., Methodology/principal Findings: From January 2004 to July 2008, ninety-seven consecutive gastric or gastroesophageal junction adenocarcinoma patients in stages T3-4/N+ were treated with postoperative radiotherapy and chemotherapy. The recommended treatment plan was radical resection followed by 1-2 cycles of adjuvant chemotherapy (ACT), postoperative chemoradiotherapy (CRT), and, finally, 4-5 cycles of ACT. The patients were classified into two groups depending on the number of cycles of ACT: group 1 received 4-6 cycles (n = 59), and group 2 received 0-3 cycles (n = 38). The detailed grouping is as follows: RT alone, 2; RT and CT, 18; concurrent RTCT and CT, 41; and CRT, 36. Of the 97 patients, 77 patients received concurrent therapy (CRT, (5-fluorouracil or capecitabine), and 20 received radiotherapy alone because of patient refusal (n = 15) or treatment toxicity (n = 5). After a median follow-up of 44 months, the 3-year disease free survival(DFS) and overall survival (OS) were 66.5% and 69.5% for group 1 and 45.5% and 50% for group 2, respectively (p = 0.005 and p = 0.024). Multivariate analysis revealed that 4-6 cycles of ACT, lymphovascular invasion, or peritoneal metastasis were independent prognostic factors for disease-free survival or overall survival (p<0.05)., Conclusions/significance: This study demonstrates that concurrent chemoradiation with adjuvant epirubicin-based triplet chemotherapy is feasible and tolerable for gastric or gastroesophageal junction carcinoma patients. Patients can benefit from more cycles of ACT.

Background: The increased risk of gastrointestinal (GI) cancers after Hodgkin's lymphoma (HL) is well established. However, no large population-based study has described the actuarial survival after subsequent GI cancers in HL survivors (HL-GI)., Patients and Methods: For 209 patients with HL-GI cancers (105 colon, 35 stomach, 30 pancreas, 21 rectum, and 18 esophagus) and 484 165 patients with first primary GI cancers (GI-1), actuarial survival was compared, accounting for age, gender, race, GI cancer stage, radiation for HL, and other variables., Results: Though survival of HL patients who developed localized stage colon cancer was similar to that of the GI-1 group, overall survival (OS) of HL patients with regional or distant stage colon cancer was reduced [hazard ratio, (HR)=1.46, P=0.01]. The HL survivors with regional or distant stage colon cancer in the transverse segment had an especially high risk of mortality (HR: 2.7, P=0.001 for OS). For localized stomach cancer, OS was inferior among HL survivors (HR=3.46, P=0.006)., Conclusions: The HL patients who develop GI cancer experience significantly reduced survival compared with patients with a first primary GI cancer. Further research is needed to explain the inferior survival of HL patients and to define selection criteria for cancer screening in HL survivors.

The management of neuroendocrine tumours is challenging when curative surgery is ruled out because of distant metastases. We report a case of gastrointestinal carcinoid with bilateral ovarian metastases in a 50-year-old female who received octreotide therapy followed by peptide receptor radionuclide therapy and surgery thereafter. Somatostatin receptor expression on neuroendocrine tumours has implications in diagnosis and therapy. (68)Ga-DOTA-NOC PET is a recent advancement in the field of somatostatin receptor imaging. The lesions which demonstrate tracer uptake on positron emission tomographic studies can be further planned for treatment with octreotide and (177)Lu-DOTA-TATE. The case in discussion responded well to non-invasive treatment options before proceeding to definitive surgical management.

There is broad consensus on surgical resection being the backbone of curative therapy of gastric- and gastroesophageal junction carcinoma. Nevertheless, details on therapeutic approaches in addition to surgery, such as chemotherapy, radiotherapy or radiochemotherapy are discussed controversially; especially whether external beam radiotherapy should be applied in addition to chemotherapy and surgery is debated in both entities and differs widely between regions and centers. Early landmark trials such as the Intergroup-0116 and the MAGIC trial must be interpreted in the context of potentially insufficient lymph node resection. Despite shortcomings of both trials, benefits on overall survival by radiochemotherapy and adjuvant chemotherapy were confirmed in populations of D2-resected gastric cancer patients by Asian trials.Recent results on junctional carcinoma patients strongly suggest a survival benefit of neoadjuvant radiochemotherapy in curatively resectable patients. An effect of chemotherapy in the perioperative setting as given in the MAGIC study has been confirmed by the ACCORD07 trial for junctional carcinomas; however both the studies by Stahl et al. and the excellent outcome in the CROSS trial as compared to all other therapeutic approaches indicate a superiority of neoadjuvant radiochemotherapy as compared to perioperative chemotherapy in junctional carcinoma patients. Surgery alone without neoadjuvant or perioperative therapy is considered suboptimal in patients with locally advanced disease.In gastric carcinoma patients, perioperative chemotherapy has not been compared to adjuvant radiochemotherapy in a randomized setting. Nevertheless, the results of the recently published ARTIST trial and the Chinese data by Zhu and coworkers, indicate a superiority of adjuvant radiochemotherapy as compared to adjuvant chemotherapy in terms of disease free survival in Asian patients with advanced gastric carcinoma. The ongoing CRITICS trial is supposed to provide reliable conclusions about which therapy should be preferred in Western patients with gastric carcinoma. If radiotherapy is performed, modern approaches such as intensity-modulated radiotherapy and image guidance should be applied, as these methods reduce dose to organs at risk and provide a more homogenous coverage of planning target volumes.

Nuclear medicine plays a pivotal role in the imaging and treatment of neuroendocrine tumours (NETs). Somatostatin receptor scintigraphy (SRS) with [(111)In-DTPA(0)]octreotide has proven its role in the diagnosis and staging of gastroenteropancreatic NETs (GEP-NETs). New techniques in somatostatin receptor imaging include the use of different radiolabelled somatostatin analogues with higher affinity and different affinity profiles to the somatostatin receptor subtypes. Most of these analogues can also be labelled with positron-emitting radionuclides that are being used in positron emission tomography imaging. The latter imaging modality, especially in the combination with computed tomography, is of interest because of encouraging results in terms of improved imaging quality and detection capabilities. Considerable advances have been made in the imaging of NETs, but to find the ideal imaging method with increased sensitivity and better topographic localisation of the primary and metastatic disease remains the ultimate goal of research. This review provides an overview of the currently used imaging modalities and ongoing developments in the imaging of NETs, with the emphasis on nuclear medicine and puts them in perspective of clinical practice. The advantage of SRS over other imaging modalities in GEP-NETs is that it can be used to select patients with sufficient uptake for treatment with radiolabelled somatostatin analogues. Peptide receptor radionuclide therapy (PRRT) is a promising new tool in the management of patients with inoperable or metastasised NETs as it can induce symptomatic improvement with all Indium-111, Yttrium-90 or Lutetium-177-labelled somatostatin analogues. The results that were obtained with [(90)Y-DOTA(0),Tyr(3)]octreotide and [(177)Lu-DOTA(0),Tyr(3)]octreotate are even more encouraging in terms of objective tumour responses with tumour regression and documented prolonged time to progression. In the largest group of patients receiving PRRT, treated with [(177)Lu-DOTA(0),Tyr(3)]octreotate, a survival benefit of several years compared with historical controls has been reported.

In this retrospective study medical records of 11 cats with gastrointestinal lymphoma were evaluated to determine the efficacy of radiation therapy when used in a rescue therapy setting. All cats had relapsed or resistant lymphoma. Two fractions of radiation were delivered over 2 days for a total of 800cGy. Acute effects of radiation were not noted, except one cat that had a self-limiting loss of appetite. Response was noted in 10/11 cats. Median survival post-radiation therapy was 214 days and the overall median survival in this study was 355 days. This study suggests that abdominal irradiation for feline gastrointestinal lymphoma was well tolerated and may contribute to a positive clinical response., (Copyright © 2010 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.)

High dose rate (HDR) brachytherapy is one of the accepted treatment modalities in gastro-intestinal tract and bladder carcinomas. Considering the shortcoming of contact brachytherapy routinely used in gastrointestinal tract in treatment of big tumors or invasive method of bladder treatment, an intraluminal applicator with the capability of insertion into the tumor depth seems to be useful. This study presents some dosimetric evaluations to introduce this applicator to the clinical use. The radiation attenuation characteristics of the applicator were evaluated by means of two dosimetric methods including well-type chamber and radiochromic film. The proposed 110 cm long applicator has a flexible structure made of stainless steel for easy passage through lumens and a needle tip to drill into big tumors. The 2mm diameter of the applicator is thick enough for source transition, while easy passage through any narrow lumen such as endoscope or cystoscope working channel is ensured. Well-chamber results showed an acceptably low attenuation of this steel springy applicator. Performing absolute dosimetry resulted in a correlation coefficient of R = 0.9916 (p-value ≈ 10-7) between standard interstitial applicator and the one proposed in this article. This study not only introduces a novel applicator with acceptable attenuation but also proves the response independency of the GAFCHROMIC EBT films to energy. By applying the dose response of the applicator in the treatment planning software, it can be used as a new intraluminal / interstitial applicator.

Background: Intrahepatic cholangiocarcinoma (ICC) is the second most common type of primary liver cancer. Only few studies have focused on palliative radiotherapy used for patients who weren't suitable for resection by surgery. This study was conducted to investigate the effect of external beam radiotherapy (EBRT) for patients with unresectable ICC., Methods: We identified 84 patients with ICC from December 1998 through December 2008 for retrospective analysis. Thirty-five of 84 patients received EBRT therapy five times a week (median dose, 50 Gy; dose range, 30-60 Gy, in fractions of 1.8-2.0 Gy daily; EBRT group); the remaining 49 patients comprised the non-EBRT group. Tumor response, jaundice relief, and survival rates were compared by Kaplan-Meier analysis. Patient records were reviewed and compared using Cox proportional hazard analysis to determine factors that affect survival time in ICC., Results: After EBRT, complete response (CR) and partial response (PR) of primary tumors were observed in 8.6% and 28.5% of patients, respectively, and CR and PR of lymph node metastases were observed in 20% and 40% of patients. In 19 patients with jaundice, complete and partial relief was observed in 36.8% and 31.6% of patients, respectively. Median survival times were 5.1 months for the non-EBRT group and 9.5 months for the EBRT group (P = 0.003). One-and two-year survival rates for EBRT versus non-EBRT group were 38.5% versus 16.4%, and 9.6% versus 4.9%, respectively. Multivariate analysis revealed that clinical symptoms, larger tumor size, no EBRT, multiple nodules and synchronous lymph node metastases were associated with poorer prognosis., Conclusions: EBRT as palliative care appears to improve prognosis and relieve the symptom of jaundice in patients with unresectable ICC.

Introduction: Retrospective analyses were performed on the patients with primary or metastatic lung cancer, who were treated with hypofractionated stereotactic radiation therapy (HSRT)., Methods: HSRT was applied to 43 patients since 2001 till 2007: 16 patients were with stage I primary lung cancer and 27 were with metastasis. Radiation was delivered in five consecutive daily fractions. The total doses were 50 Gy to 8 patients and 60 Gy to 35 patients. The median follow-up period was 21 months (range, 3-87 months). The effects of tumor size (<2.5 cm versus >or=2.5 cm) and radiation dose (50 Gy/5 fractions versus 60 Gy/5 fractions) on local tumor control were evaluated., Results: Local tumor progression occurred in three patients (6.9%). The 5-year local progression-free survival and cancer-specific survival rate were 89.4 and 53.3%, respectively. Tumors <2.5 cm resulted in higher crude local tumor control rate than tumors more than or equal to 2.5 cm (100.0% versus 82.3%, p = 0.05). In tumors more than or equal to 2.5 cm, the local tumor control rate was 66.7% with 50 Gy/5 fractions and 85.7% with 60 Gy/5 fractions (p = 0.46)., Conclusions: In HSRT for primary or metastatic lung cancers, smaller tumor size was significant prognostic factor for higher local control. Higher radiation dose than 50 Gy/5 fractions was needed in tumors more than or equal to 2.5 cm for local tumor control.

Background: Reirradiation to the abdomen could potentially play a role in palliation of symptoms or local control in patients with gastrointestinal malignancies. Our goal was to retrospectively determine rates of toxicity, freedom from local progression and overall survival in gastrointestinal cancer patients treated with reirradiation to the abdomen., Methods: Between November 2002 and September 2008, 13 patients with a prior history of abdominal radiotherapy (median dose 45 Gy) were treated with reirradiation for recurrent or metastatic gastrointestinal malignancies. The median interval between the two courses of radiotherapy was 26 months. Patients were treated with a hyperfractionated accelerated regimen, using 1.5 Gy fractions twice daily, with a median dose of 30 Gy (range 24-48 Gy). Concurrent chemotherapy was administered to 8 (62%) patients., Results: The 1-year rate of freedom from local progression was 50%, and the median duration of freedom from local progression was 14 months. The 1-year rate of overall survival was 62%, and the median duration of overall survival was 14 months. One patient developed grade 3 acute toxicity (abdominal pain and gastrointestinal bleeding), requiring hospitalization during radiotherapy; subsequently, that patient experienced a grade 4 late toxicity (gastrointestinal bleeding). No other patients developed grade 3-4 acute or late toxicity or required hospitalization during radiotherapy., Conclusion: Hyperfractionated accelerated reirradiation to the abdomen was well-tolerated with low rates of acute and late toxicity. Reirradiation could play a role in providing a limited duration of local control in gastrointestinal cancer patients with a history of prior abdominal radiotherapy.

Purpose: In preclinical models, radioimmunotherapy with (131)I-A5B7 anti-carcinoembryonic antigen (CEA) antibody ((131)I-A5B7) combined with the vascular disruptive agent combretastatin-A4-phosphate (CA4P) produced cures unlike either agent alone. We conducted a phase I trial determining the dose-limiting toxicity (DLT), maximum tolerated dose, efficacy, and mechanism of this combination in patients with gastrointestinal adenocarcinomas., Experimental Design: Patients had CEA of 10 to 1,000 microg/L, QTc < or =450 ms, no cardiac arrhythmia/ischaemia, and adequate hematology/biochemistry. Tumor was suitable for blood flow analysis by dynamic contrast enhanced-magnetic resonance imaging (MRI). The starting dose was 1,800 MBq/m(2) of (131)I-A5B7 on day 1 and 45 mg/m(2) CA4P given 48 and 72 hours post-(131)I-A5B7, then weekly for up to seven weeks., Results: Twelve patients were treated, with mean age of 63 years (range, 32-77). Two of six patients at the first dose level had DLTs (grade 4 neutropenia). The dose was reduced to 1,600 MBq/m(2), and CA4P escalated to 54 mg/m(2). Again, two of six patients had DLTs (neutropenia). Of ten assessable patients, three had stable disease and seven had progressive disease. Single-photon emission computed tomography confirmed tumor antibody uptake in all 10 patients. DCE-MRI confirmed falls in kinetic parameters (K(trans)/IAUGC(60)) in 9 of 12 patients. The change of both pharmacokinetic parameters reached a level expected to produce efficacy in one patient who had a minor response on computed tomography and a reduced serum tumor marker level., Conclusions: This is believed to be the first trial reporting the combination of radioimmunotherapy and vascular disruptive agent; each component was shown to function, and myelosuppression was dose-limiting. Optimal dose and timing of CA4P, and moderate improvements in the performance of radioimmunotherapy seem necessary for efficacy.

Objective: The objective of this retrospective study was to report the clinicopathological data and the treatment outcomes in patients with primary gastrointestinal non-Hodgkin's lymphoma., Patients and Methods: We carried out a retrospective analysis of 41 patients (22 females, 18 males, median age 58 and range 18-90 years) who presented to our department with histopathological diagnosis of primary gastrointestinal non-Hodgkin's lymphoma between 1995 and 2004., Results: The stomach was the most common extranodal site and was seen in 25 of 41 (61%) patients. At presentation 28 (68.3%) patients had gastrointestinal symptoms while 27 (65.9%) had B symptoms. The range of follow-up was 2-84 months with a median of 9 months. The overall survival rate was 3 years for 25 (61.2%) patients. The 3-year overall survival rate was better in patients with early-stage disease (stages I and II(1)) who were treated with surgery plus chemotherapy and/or radiation therapy than in those treated with chemotherapy alone (91.6 vs. 50%, p < 0.05). The disease had a significant impact on both the progression-free survival and overall survival rates., Conclusion: Our data showed that surgical resection prior to postoperative chemotherapy was a better option for patients with early-stage disease with better patient survival., (Copyright 2009 S. Karger AG, Basel.)

A 45-year-old white male presented to our department with postoperative recurrence of gastrointestinal poorly differentiated neuroendocrine carcinoma manifesting as lymph node dissemination and a solitary implantation metastasis in the rectovesical pouch. Following disease progression on chemotherapy, the patient was treated with radiotherapy using either a conventional daily treatment or an accelerated hyperfractionated protocol to separate sites of disease progression. Using serial CT scan assessment, changes in cross-sectional area of the separately treated metastatic lesions were evaluated for determination of therapy response. The accelerated hyperfractionated radiotherapy appeared to limit the rate of tumor growth to a greater degree than the conventional fractionation schedule. Of uttermost importance, in this palliative setting, the patient completed the intensified radiotherapy regimens with acceptable acute toxicity. Given the proliferative capacity of poorly differentiated neuroendocrine carcinomas of the gastrointestinal tract, radiotherapy may be a therapeutic supplement to chemotherapy, which represents the main treatment option in this tumor entity. Importantly, tumors with a capacity for rapid proliferation and regeneration may be particularly sensitive to the use of intensified fractionation protocols in clinical radiotherapy.

Background: Reliable, non-invasive biological markers of the severity of radiotherapy-induced damage to the gastrointestinal tract are not available. Clinicians continue to use symptom scores as surrogate indicators of toxicity., Aim: To determine whether levels of potential biochemical markers of mucosal toxicity change during pelvic radiotherapy., Methods: Fifty-nine patients (30:29 males:females) with mixed pelvic malignancies, receiving 45-70 Gy were recruited. At baseline and weeks 4 or 5 of radiotherapy, blood samples for citrulline, C-reactive protein, eosinophil cationic protein and stool samples for faecal calprotectin were obtained. Symptoms were measured using the Inflammatory Bowel Disease Questionnaire - Bowel Subset, Radiation Therapy Oncology Group and Vaizey Incontinence Questionnaires. Paired t-tests of change in marker values were calculated., Results: Citrulline (P = 0.02) and faecal calprotectin (P = 0.01) values changed significantly between baseline and 4/5 weeks. Inflammatory Bowel Disease Questionnaire - Bowel Subset fell significantly (mean fall = 10 points, s.d.: 8.9). Changes in markers did not correlate with symptoms., Conclusions: Some biochemical markers of mucosal toxicity change significantly during treatment. Further studies must investigate the timing of changes of these biochemical markers, their relationship to gastrointestinal physiological change and the radiotherapy dose delivered to the gastrointestinal tract and whether changes in markers acutely can predict the degree of long-term gastrointestinal dysfunction.

Objective: Malnutrition occurs frequently in cancer patients and is multifactorial and can lead to negative outcomes. So we studied the effect of radiotherapy on nutritional status, weight changes, dietary intake, serum zinc and copper levels., Methods: During the period of October to March 2005, 45 cancer patients who referred to the Radiotherapy Center, Imam Khomeini Hospital, Iran were recruited. We assessed the nutritional status of patients using Patient-Generated Subjective Global Assessment (PG-SGA) questionnaire. Patients on the basis of location of radiotherapy classified to mediastinum, head and neck and pelvic groups. Changes in dietary intake (using 24-hour recall method) and body weight were evaluated prior to and during radiotherapy. At the onset and the end of radiotherapy, serum levels of zinc, copper and albumin were determined., Results: After treatment malnutrition increased significantly in all patients (p=0.01) and in head and neck (p=0.007) and pelvic groups (p=0.04). The decreased body weight of patients was significant in the head and neck (p=0.02), and pelvic groups (p=0.005). The mean daily energy and protein intake of head and neck and pelvic groups decreased during radiotherapy while energy intake increased significantly in mediastinum group (p=0.01). After treatment, significant decreases also observed in mean serum zinc, copper and albumin levels (p<0.05)., Conclusion: Because of the negative effect of radiotherapy on oral feeding, nutritional assessment and intervention should be an integral part of treatment. Also, it would be worthwhile studying the effect of zinc supplementation on dietary intake and nutritional status of patients.

We retrospectively evaluated acute toxicity in 88 patients that were treated with capecitabine and concurrent radiotherapy to the upper abdomen. These patients included 28 (32%) with pancreatic adenocarcinoma, 18 (20%) with cholangiocarcinoma, 11 (13%) with ampullary carcinoma, 11 (13%) with other primary tumors, 14 (16%) with liver metastases, and 6 (7%) with metastases at other sites. The median dose of radiotherapy was 45 Gy (range 30-72 Gy). The median dose of capecitabine was 850 mg/m(2) twice daily, with 77% receiving 800-900 mg/m(2) twice daily. The highest grade of acute toxicity was Common Terminology Criteria (CTC) grade 0 in 5 (6%), grade 1 in 60 (68%), grade 2 in 18 (20%), and grade 3 in 5 (6%) patients. No patient had CTC grade 4 toxicity. The most common grade 2 toxicities were nausea, hand-foot syndrome, fatigue, anorexia and diarrhea. The grade 3 toxicities included nausea, vomiting and fatigue. Three patients (3%) required hospitalization due to grade 3 acute toxicity. Capecitabine was interrupted, discontinued or given at an adjusted dose in 13 (15%) patients because of acute toxicity. Therefore, capecitabine and concurrent radiotherapy to the upper abdomen appears to be well tolerated. Capecitabine may serve as an alternative to bolus or infusional 5-FU during chemoradiation for upper gastrointestinal malignancies.

Context: Daily setup errors and changes in body habitus during external beam radiotherapy can result in interfraction variation, contributing to uncertainties in treatment delivery. The conventional method of patient positioning using external skin markings is inadequate in reducing these interfraction variations., Objective: To evaluate use of on-board imaging with daily kV-kV image matching to reduce interfraction variation in patients with primary gastrointestinal cancer., Patients: To evaluate interfraction variation, 13 patients underwent radiotherapy for primary non-metastatic gastrointestinal cancer as did 1 patient with renal liposarcoma., Interventions: After conventional external setup, kV-kV image matching was performed using bony landmarks or radiopaque surgical clips with a Varian on-board imager. The degree of shift between the real-time patient position and the planning position were recorded in three planes, and appropriate corrections were made for treatment., Main Outcome Measures: Degree of shift, acute toxicity and local response were assessed., Results: For 276 daily on-board imaging sessions, average shift was 0.30+/-0.42 cm (vertical), 0.33+/-0.34 cm (longitudinal), and 0.35+/-0.39 cm (lateral); average 3-D vector shift was 0.71+/-0.52 cm. Percentage of shift greater than or equal to 0.5 cm was 25% (vertical), 28% (longitudinal), and 30% (lateral); percentage of total vector shift greater than or equal to 0.5 cm was 64%. The pattern of shifts showed a random distribution over time. At median 6-month follow-up, 3 (21%) patients had radiographic local disease regression, ten (71%) had local disease stabilization, and 1 (7%) had local progression., Conclusion: Use of daily on-board imaging kV-kV matching reduced uncertainty in amount of dose delivered, potentially resulting in improvement in local control and reduction in treatment toxicity.

A 68-year-old woman presented with an extremely rare intracranial metastasis from a gastrointestinal stromal tumor (GIST) manifesting as left hemiparesis 2 years after resection of a sacral tumor adjacent to the coccygeal bone. Magnetic resonance imaging revealed an intracranial tumor in the right parietal lobe. Craniotomy was performed to completely remove the tumor. Although the tumor was located extra-axially, only internal carotid angiography showed mass staining. Seven months after surgery, the tumor recurred. Repeat craniotomy was performed to remove the recurrent tumor. Immunohistochemical analysis showed that the tumor cells were positive for c-kit and CD34, and the tumors were identified as intracranial metastasis of GIST. Following the second intracranial surgery, the patient developed severe lower back pain caused by metastatic tumor invading the lumbar spine and ureter. To avoid surgical complications and to reduce tumor volume, imatinib mesylate (Gleevec) was administered. The severe pain was relieved, although the tumor was not reduced. In this case, the extra-axial tumor was fed only by the internal carotid artery.

Unlabelled: Peptide receptor scintigraphy in combination with anatomic imaging methods such as CT can be regarded as molecular imaging. It offers insight into the variability of somatostatin receptor expression in neuroendocrine tumor lesions within a patient. The somatostatin receptor status of all tumors in a patient is an important issue, because receptor-negative lesions may be poorly differentiated and characterized by aggressive growth and poor prognosis, with consequences for the choice of therapy., Methods: Follow-up studies of 3 patients with gastroenteropancreatic neuroendocrine tumors who had been previously treated with peptide receptor radionuclide therapy (PRRT) are presented., Results: Patient 1 had a mixed response after treatment with (90)Y-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid(0) (DOTA),Tyr(3)-octreotide. The response included fibrosis and a low rate of mitosis in receptor-positive lesions that had decreased in volume after treatment and vital tumor cells and a high rate of mitosis in receptor-negative lesions that had grown since the start of treatment. Patient 2 had a good clinical and biochemical response after PRRT with [(177)Lu-DOTA(0),Tyr(3)]octreotate ((177)Lu-DOTATATE), with disappearance of (111)In-pentetreotide uptake on follow-up scans, whereas on CT the size of the lesions remained unchanged, possibly indicating tumor necrosis. Patient 3 had a complete remission after PRRT with (177)Lu-DOTATATE but subsequently relapsed with many receptor-negative metastases, requiring intensive chemotherapy., Conclusion: Although biopsy is required for initial diagnosis and treatment planning, noninvasive molecular imaging may evolve into in vivo molecular pathology in selected groups of patients, especially in treatment follow-up.

Unlabelled: Nephrotoxicity is the major limiting factor during therapy with the radiolabeled somatostatin analog (90)Y-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA)-d-Phe(1)-Tyr(3)-octreotide (DOTATOC). Pretherapeutic assessment of kidney absorbed dose could help to minimize the risk of renal toxicity. The aim of this study was to evaluate the contribution of patient-specific adjustments to the standard dosimetric models, such as the renal volume and dose rate, for estimating renal absorbed dose during therapy with (90)Y-DOTATOC. In particular, we investigated the correlation between dose estimates and effect on renal function after therapy., Methods: Eighteen patients with neuroendocrine tumors (9 men and 9 women; median age, 59 y) underwent treatment with (90)Y-DOTATOC (8.1-22.9 GBq) after pretherapeutic biodistribution study with (86)Y-DOTATOC. Kidney uptake and residence times were measured and the absorbed dose (KAD) was computed using either the MIRDOSE3.1 software assuming a standard kidney volume (KAD(StdVol)) or the MIRD Pamphlet 19 values and the actual kidney cortex volume determined by pretherapeutic CT (KAD(CTVol)). For each patient, the biologic effective dose (BED) was calculated according to the linear quadratic model to take into account the effect of dose rate and fractionation. Renal function was evaluated every 6 mo by serum creatinine and creatinine clearance (CLR) during a median follow-up of 35.5 mo (range, 18-65 mo). The individual rate of decline of renal function was expressed as CLR loss per year., Results: KAD(CTVol) ranged between 19.4 and 39.6 Gy (mean, 28.9 +/- 5.34 Gy). BED, obtained from KAD(CTVol), ranged between 27.7 and 59.3 Gy (mean, 40.4 +/- 10.6 Gy). The CLR loss per year ranged from 0% to 56.4%. In 12 of 18 patients, CLR loss per year was <20%. No correlation was observed between CLR loss per year and the KAD(StdVol) or the KAD(CTVol). In contrast, BED strongly correlated with CLR loss per year (r = 0.93; P < 0.0001). All 5 patients with CLR loss per year >20% received a BED >45 Gy. Patients who were treated with low fractionation were those with the highest rate of renal function impairment., Conclusion: Radiation nephrotoxicity after (90)Y-DOTATOC therapy is dose dependent. Individual renal volume, dose rate, and fractionation play important roles in an accurate dosimetry estimation that enables prediction of risk of renal function impairment.