Primary Treatment for Clinically Early Cervical Cancer with Lymph Node Metastasis:Radical Surgery or Radiation?

Objective To compare survival outcomes between primary radical surgery and primary radiation in early cervical cancer.Methods Patient information was extracted from the Surveillance,Epidemiology,and Results database.Patients diagnosed with early cervical cancer of stage T1a,T1b,and T2a(American Joint Committee on Cancer,7th edition)from 1998 to 2015 were included in this study after propensity score matching.Overall survival(OS)was analyzed using the Kaplan-Meier method.Results Among the 4964 patients included in the study,1080 patients were identified as having positive lymph nodes(N1),and 3884 patients were identified as having negative lymph nodes(N0).Patients with primary surgery had significantly longer 5-year OS than those with primary radiotherapy in both the N1 group(P<0.001)and N0 group(P<0.001).In the subgroup analysis,similar results were found in patients with positive lymph nodes of stage T1a(100.0%vs.61.1%),T1b(84.1%vs.64.3%),and T2a(74.4%vs.63.8%).In patients with T1b1 and T2a1,primary surgery resulted in longer OS than primary radiation,but not in patients with T1b2 and T2a2.In multivariate analysis,the primary treatment was identified as an independent prognostic factor in both N1 and N0 patients(HR_(N1)=2.522,95%CI=1.919–3.054,PN1<0.001;HR_(N0)=1.895,95%CI=1.689–2.126,PN0<0.001).Conclusion In early cervical cancer stage T1a,T1b1,and T2a1,primary surgery may result in longer OS than primary radiation for patients with and without lymph node metastasis.

Spinal cord biological safety of image-guided radiation therapy versus conventional radiation therapy

Tumor models were simulated in purebred Beagles at the T9-10 levels of the spinal cord and treated with spinal image-guided radiation therapy or conventional radiation therapy with 50 or 70 Gy total radiation. Three months after radiation, neuronal injury at the T9-10 levels was observed, including reversible injury induced by spinal image-guided radiation therapy and apoptosis induced by conventional radiation therapy. The number of apoptotic cells and expression of the proapoptotic protein Fas were significantly reduced, but expression of the anti-apoptotic protein heat shock protein 70 was significantly increased after image-guided radiation therapy compared with the conventional method of the same radiation dose. Moreover, the spinal cord cell apoptotic index positively correlated with the ratio of Fas/heat shock protein 70. These findings indicate that 3 months of radiation therapy can induce a late response in the spinal cord to radiation therapy; image-guided radiation therapy is safer and results in less neuronal injury compared with conventional radiation therapy.

Gastrointestinal radiation injury:Prevention and treatment

With the recent advances in detection and treatment of cancer,there is an increasing emphasis on the efficacy and safety aspects of cancer therapy.Radiation therapy is a common treatment for a wide variety of cancers,either alone or in combination with other treatments.Ionising radiation injury to the gastrointestinal tract is a frequent side effect of radiation therapy and a considerable proportion of patients suffer acute or chronic gastrointestinal symptoms as a result.These side effects often cause morbidity and may in some cases lower the efficacy of radiotherapy treatment.Radiation injury to the gastrointestinal tract can be minimised by either of two strategies:technical strategies which aim to physically shift radiation dose away from the normal intestinal tissues,and biological strategies which aim to modulate the normal tissue response to ionising radiation or to increase its resistance to it.Although considerable improvement in the safety of radiotherapy treatment has been achieved through the use of modern optimised planning and delivery techniques,biological techniques may offer additional further promise.Different agents have been used to prevent or minimize the severity of gastrointestinal injury induced by ionising radiation exposure,including biological,chemical and pharmacological agents.In this review we aim to discuss various technical strategies to prevent gastrointestinal injury during cancer radiotherapy,examine the different therapeutic options for acute and chronic gastrointestinal radiation injury and outline some examples of research directions and considerations for prevention at a pre-clinical level.

Endoscopic treatments for chronic radiation proctitis

Chronic radiation proctitis is a complication that occurs in patients who receive radiation therapy for pelvic malignancies. The common presentation is with rectal bleeding, but also rectal pain, diarrhea, tenesmus and even passage of mucus can occur. The optimal treatment of bleeding due to radiation proctitis remains unclear. Among various therapeutic options, medical management is generally ineffective and surgical intervention has a high incidence of morbidity. Promising advances have been made in endoscopic therapy, including argon plasma coagulation (APC), formalin application as well as new techniques such as radio-frequency ablation and cryoablation. APC is a safe, highly effective and long-lasting therapy in patients with rectal bleeding associated with radiation proctitis. It has been shown that several sessions of APC reduce the rate of bleeding and therefore the blood transfusion requirements. Moreover, the effect of treatment is long lasting. However, best results are achieved in patients with mild to moderate radiation proctitis, leaving space for alternative treatments for patients with more severe disease. In patients with severe or refractoryradiation proctitis intra rectal formalin application is an appropriate treatment option. Radiofrequency ablation and cryoablation have shown efficacy as alternative methods in a limited number of patients with refractory chronic radiation proctitis.

Chronic radiation proctopathy: A practical review of endoscopic treatment

Chronic radiation proctopathy(CRP) is a troublesome complication of pelvic radiotherapy. The most common presentation is rectal bleeding. CRP symptoms interfere with daily activities and decrease quality of life. Rectal bleeding management in patients with CRP represents a conundrum for practitioners. Medical therapy is ineffective in general and surgical approach has a high morbidmortality. Endoscopy has a role in the diagnosis,staging and treatment of this disease. Currently available endoscopic modalities are formalin,potassium titanyl phosphate laser,neodymium:yttrium-aluminum-garnet laser,argon laser,bipolar electrocoagulation(BiCAP),heater probe,band ligation,cryotherapy,radiofrequency ablation and argon plasma coagulation(APC). Among these options,APC is the most promising.

Review of treatment assessment using DCE-MRI in breast cancer radiation therapy

As a noninvasive functional imaging technique, dynamic contrast-enhanced magnetic resonance imaging(DCEMRI) is being used in oncology to measure properties of tumor microvascular structure and permeability. Studies have shown that parameters derived from certain pharmacokinetic models can be used as imaging biomarkers for tumor treatment response. The use of DCE-MRI for quantitative and objective assessment of radiation therapy has been explored in a variety of methods and tumor types. However, due to the complexity in imaging technology and divergent outcomes from different pharmacokinetic approaches, the method of using DCE-MRI in treatment assessment has yet to be standardized, especially for breast cancer. This article reviews the basic principles of breast DCE-MRI and recent studies using DCE-MRI in treatment assessment. Technical and clinical considerations are emphasized with specific attention to assessment of radiation treatment response.

Application of positron emission tomography/computed tomography in radiation treatment planning for head and neck cancers

18-fluorodeoxygluocose positron emission tomography/computed tomography(18FDG-PET/CT) provides significant information in multiple settings in the management of head and neck cancers(HNC). This article seeks to define the additional benefit of PET/CT as related to radiation treatment planning for squamous cell carcinomas(SCCs) of the head and neck through a review of relevant literature. By helping further define both primary and nodal volumes, radiation treatment planning can be improved using PET/CT. Special attention is paid to the independent benefit of PET/CT in targeting mucosal primaries as well as in detecting nodal metastases. The utility of PET/CT is also explored for treatment planning in the setting of SCC of unknown primary as PET/CT may help define a mucosal target volume by guiding biopsies for examination under anesthesia thus changing the treatment paradigm and limiting the extent of therapy. Implications of the use of PET/CT for proper target delineation in patients with artifact from dental procedures are discussed and the impact of dental artifact on CT-based PET attenuation correction is assessed. Finally, comment is made upon the role of PET/CT in the high-risk post-operative setting, particularly in the context of radiation dose escalation. Real case examples are used in these settings to elucidate the practical benefits of PET/CT as related to radiation treatment planning in HNCs.

CT image fusion in the evaluation of radiation treatment planning for non-small cell lung cancer

Objective: We studied the application of CT image fusion in the evaluation of radiation treatment planning for non-small cell lung cancer (NSCLC). Methods: Eleven patients with NSCLC, who were treated with three-dimensional con-formal radiation therapy, were studied. Each patient underwent twice sequential planning CT scan, i.e., at pre-treatment, and at mid-treatment for field reduction planning. Three treatment plans were established in each patient: treatment plan A was based on the pre-treatment planning CT scans for the first course of treatment, plan B on the mid-treatment planning CT scans for the second course of treatment, and treatment plan F on the fused images for the whole treatment. The irradiation doses received by organs at risk in the whole treatment with treatment A and B plans were estimated by the plus of the parameters in treatment plan A and B, assuming that the parameters involve the different tissues (i.e. V20=AV20+BV20), or the same tissues within an organ (i.e. Dmax=ADmax+BDmax). The assessment parameters in the treatment plan F were calculated on the basis of the DVH of the whole treatment. Then the above assessment results were compared. Results: There were marked differ-ences between the assessment results derived from the plus of assessment parameters in treatment plan A and B, and the ones derived from treatment plan F. Conclusion: When a treatment plan is altered during the course of radiation treatment, image fusion technique should be performed in the establishment of a new one. The estimation of the assessment parameters for the whole treatment with treatment plan A and B by simple plus, is inaccurate.

Qing Dai, a traditional Chinese medicine for the treatment of chronic hemorrhagic radiation proctitis

Objective： To evaluate the efficacy and safety of Qing Dai （indigo naturalis）, a traditional Chinese medicine, in the treatment for chronic hemorrhagic radiation proctitis. Methods： Ten patients with chronic hemorrhagic radiation proctitis between January 2005 to January 2008 were treated with Qing Dai. Qing Dai was administered orally at a dose of 1.5 g, bid for 5 consecutive days, every 2 weeks for two courses. Patients were followed up every 3 months. The clinical response and side-effects were evaluated. Results： Six patients showed improvement of rectal bleeding to grade 0-1 after 1 course of Qing Dai therapy. Four patients had reduced rectal bleeding to grade 0-1 after 2 courses of the therapy. The median follow-up time was 10 months （range： 6-24）. During the follow-up period, 1 patient experienced recurrent rectal bleeding and was managed with topical formalin dabbing, which controlled the symptom. No treatment toxicity was observed. Conclusion： Qing Dai may be a safe and effective treatment for chronic hemorrhagic radiation proctitis.

Treatment outcomes for different subgroups of nasopharyngeal carcinoma patients treated with intensity-modulated radiation therapy

Although many studies have investigated intensity-modulated radiation therapy (IMRT) for nasopharyngeal carcinoma (NPC),sample sizes in the reported studies are usually small and different in outcomes in different T and N subgroups are seldom analyzed.Herein,we evaluated the outcomes of NPC patients treated with IMRT and further explored treatment strategy to improve such outcome.We collected clinical data of 865 NPC patients treated with IMRT alone or in combination with chemotherapy,and classified all cases into the following prognostic categories according to different TNM stages:early stage group (T1-2N0-1M0),advanced local disease group (T3-4N0-1M0),advanced nodal disease group (T1-2N2-3M0),and advanced locoregional disease group (T3-4N2-3M0).The 5-year overall survival (OS),local relapse-free survival (LRFS),and distant metastases-free survival (DMFS) were 83.0%,90.4%,and 84.0%,respectively.The early disease group had the lowest treatment failure rate,with a 5-year OS of 95.6%.The advanced local disease group and advanced nodal disease group had similar failure pattern and treatment outcomes as well as similar hazard ratios for death (4.230 and 4.625,respectively).The advanced locoregional disease group had the highest incidence of relapse and death,with a 5-year DMFS and OS of 62.3% and 62.2%,respectively,and a hazard ratio for death of 10.402.Comparing with IMRT alone,IMRT in combination with chemotherapy provided no significant benefit to locoregionally advanced NPC.Our results suggest that the decision of treatment strategy for NPC patients should consider combinations of T and N stages,and that IMRT alone for early stage NPC patients can produce satisfactory results.However,for advanced local,nodal,and locoregional disease groups,a combination of chemotherapy and radiotherapy is recommended.

Evaluation of 3D-CRT and VMAT Radiotherapy Plans for Left Breast Cancer with Regional Lymph Nodes Irradiation

Introduction: Radiation therapy after breast surgery is an integral part of the treatment of early breast cancer. The goal of radiation therapy is to achieve the best possible coverage of the planning target volume (PTV), while reducing the dose to organs at risk (OARs) which are normal tissues whose sensitivity to irradiation could cause damage that can lead to modification of the treatment plan. In the last decade, radiation oncologist started to use the Intensity Modulated Radiotherapy (IMRT) and Volumetric Modulated Arc Therapy (VMAT) for irradiating the breast, in order to achieve better dose distribution and target dose to the PTV and OAR. The aim of this study is to compare 2 external radiotherapy techniques (VMAT vs 3D) for patients with node-positive left breast cancer. Patients and Methods: We randomly selected 10 cases of postoperative radiotherapy for breast cancer in our hospital. The patients are all female, the average age was 45.4 years old, and the primary lesions are left breast. The ANOVA test was used to compare the mean difference between subgroups, and the p value Results: Dose volume histogram (DVH) was used to analyze each evaluation dose of clinical target volume (CTV) and organs at risk (OARs). Compared to 3DCRT plans, VMAT provided more uniform coverage to the breast and regional lymph nodes. The max point dose for tVMAT was lower on average (106.4% for VMAT versus 109% for 3DCRT). OAR sparing was improved with tVMAT, with a lower average V17Gy for the left lung (27.91% for VMAT versus 30.04% for 3DCRT, p and lower for V28Gy (13.75% for VMAT versus 22.34% for 3DCRT, p = 0.01). We also found a lower V35Gy for the heart on VMAT plan (p = 0.02). On the contrary, dose of contralateral breast was lower in 3DCRT than VMAT (0.59 Gy vs 3.65 Gy, p = 0.00). Conclusion: The both types of plans can meet the clinical dosimetry demands of postoperative radiotherapy for left breast cancer. The VMAT plan has a better conformity, but 3CDRT can provide a lower dose to the contralateral organs (breast and lung) to avoid the risk of secondary cancers.

The Impact of Small Field’s Off-Set on Output Factor in Intensity Modulated Radiation Treatment

In intensity modulated radiation treatment (IMRT) planning, the use of asymmetrically collimated fields that are placed on central axis or its off-set is mostly required. Output is the main topic discussed today for extremely small and/or severe irregularly shaped fields. The air scatter data are involved directly or indirectly in obtaining the output. Despite the fact that extensive data have been published in many studies to provide a guide on the magnitude of output factor for clinical accelerators, there are very few data reviewed about output factor in-air or phantom for off-set fields. This study was aimed to investigate the impact of these conditions for small fields. This study was conducted in Elekta Synergy linear accelerator which produces 6 MV X-ray energy. The in-air output factor (Sc) has been measured by CC04 ion chamber with brass-alloy “build-up” cap and Dose-1 electrometer, and the total output (Scp) measurements were carried on at dose maximum depth in phantom by the same chamber and Thermoluminescence dosimeter (TLD) for 1 - 10 cm2 fields. The all measurements at center of isocenter and off-set fields at three directions (X2, Y1, Diagonal) were done. By decreasing field size from 10 to 2 cm2 at isocenter, the Sc value using CC04 was decreased to 5.4% and Scp using CC04 and TLD to 14.5% and 11% respectively. By increasing off-set value, the Sc and Scp values were increased in all directions comparing to central fields. The maximum increase was obtained in Y1 direction for Sc and Scp. TLD results for Scp is slightly higher than CC04. The dosimetric properties of small fields and their off-set should be evaluated and modelled appropriately in the treatment planning system to ensure accurate dose calculation in Intensity Modulated Radiation Treatment.

Clinical Application and Prospect of New Radiotherapy Technology in Cancer Treatment

Objective: Carbon ion therapy, a new radiotherapy technology, has shown its remarkable efficacy and potential in cancer treatment, especially in the treatment of refractory tumors. Methods: This paper clarifies the physical basis, technological change, and clinical practice effect of carbon ion therapy, comprehensively discusses the future prospects, and evaluates the clinical application effect. Results: The technology has significantly improved the treatment effectiveness and received a positive response from patients. Conclusion: Carbon ion therapy technology has become a major innovation in the field of cancer treatment. It not only has a profound impact on many current cancer therapy methods but also indicates the application blueprint for a wider range of cancer types in the future, showing a new chapter of medical technology advancement.

"External main and internal auxiliary" treatment on refractory radiation proctitis

Radiotherapy is an essential method in the comprehensive treatment of malignant tumors.However,radiation proctitis(RP)is a common complication of pelvic tumors after radiotherapy.Due to RP's various etiology and complex pathogenesis,it is currently no standard for traditional Chinese medicine(TCM)treatment.Professor Yuan-hong Zhao believes that refractory RP,which is named chronic hemorrhagic radiation proctitis(CHRP),should be classified as"Intestinal Wind Bleeding"(Bleeding like a note before defecation,bright red blood,no swelling and pain in the anus)and"Intestinal Afflux"(Refers to the symptoms of pus and blood in the lower mucus,similar to ulcerative colitis,peptic ulcer and other diseases in modern medicine.)in TCM.The critical pathogenesis of CHRP lies in local stasis and collaterals injury of intestinal collaterals.In general,it is a syndrome of excess and scarcity.External treatment with TCM is the preferred treatment strategy for CHRP,and the primary way is to disperse blood stasis and detoxify and nourish the intestinal collaterals.

Professor Renting Li's Combination of Internal and External Treatment of Traditional Chinese Medicine in Treating Radiation Enteritis

Radiotherapy is a common treatment for abdominal and pelvic malignancies with bone metastases.However,some patients develop radiation enteritis(RE)during the treatment or 2 months or more after the treatment,which seriously affects their quality of life.At present,the curative effect of western medicine is poor.Professor Renting Li believes that radiation kills tumor cells but at the same time,it damages the healthy Qi of the human body.Radiation causes heat and poison to accumulate in the intestinal tract,consumes and hurts Yin fluid,bums the vein,leads to deficiency of healthy Qi and poor detoxification,as well as cause blood stasis after a period of time.All these result in the combination of heat,blood stasis,and poison,manifesting as abdominal pain,diarrhea,mucus in stools,purulent and bloody stools,etc.Therefore,Professor Renting Li proposed the use of traditional Chinese medicine retention enema combined with oral traditional Chinese medicine to reduce symptoms,remove toxins,and improve the quality of life of patients.

Role of radiation therapy in neoadjuvant era in patients with locally advanced rectal cancer

Surgery remains the primary determinant of cure in patients with localized rectal cancer, and total mesorectal excision is now widely accepted as standard of care. The widespread implementation of neoadjuvant shortcourse radiotherapy (RT) or long-course chemoradiotherapy (CRT) has reduced local recurrence rates from 25% to 40% to less than 10%; Preoperative RT in resectable rectal cancer has a number of potential advantages, most importantly reducing local recurrence, and down-staging effect. In this article making a comprehensive literature review searching the reliable medical data bases of PubMed and Cochrane we present all available information on the role of radiation therapy alone or in combination with chemotherapy in preoperative setting of rectal cancer. Data reported show that in locally advanced rectal cancer the addition of radiation therapy or CRT pre surgically has significantly improved sphincter prevention surgery. Moreover, the addition of chemotherapy to radiation therapy in preoperative setting has significantly improved pathologic complete response rate and loco-regional control rate without improvement in sphincter preserving surgery. Finally, the results of recently published randomized trials have shown a significant improvement of prevs postoperative CRT on local control; however, there was no effect on overall survival.

Endoscopic and non-endoscopic approaches for the management of radiation-induced rectal bleeding

Pelvic radiation is a commonly utilized treatment for malignancy of the genitourinary and lower gastrointestinal tract. Radiation proctitis and the resultant clinical picture varies from asymptomatic to potentially life threatening. Similarly, treatment options also vary greatly, from medical therapy to surgical intervention. Commonly utilized medical therapy includes sucralfate enemas, antibiotics, 5-aminosalicylic acid derivatives, probiotics, antioxidants, short-chain fatty acids, formalin instillation and fractionated hyperbaric oxygen. More invasive treatments include endoscopic-based, focally ablative interventions such as dilation, heater and bipolar cautery, neodymium/yttrium aluminum garnet argon laser, radiofrequency ablation or argon plasma coagulation. Despite its relatively common frequency, there is a dearth of existing literature reporting headto-head comparisons of the various treatment options via a randomized controlled approach. The purpose of our review was to present the reader a consolidation of the existing evidence-based literature with the goal of highlighting the comparative effectiveness and risks of the various treatment approaches. Finally, we outline a pragmatic approach to the treatment of radiation proctitis. In light of the lack of randomized data, our goal is to pursue as least invasive an approach as possible, with escalation of care tailored to the severity of the patient's symptoms. For those cases that are clinicallyasymptomatic or only mildly symptomatic, observation or medical management can be considered. Once a patient fails such management or symptoms become more severe, invasive procedures such as endoscopically based focal ablation or surgical intervention can be considered. Although not all recommendations are supported by level I evidence, reported case series and single-institutional studies in the literature suggest that successful treatment with cessation of symptoms can be obtained in the majority of cases.

Subcurative radiation significantly increases cell proliferation, invasion, and migration of primary glioblastoma multiforme in vivo

Tumor cell proliferation, infiltration, migration, and neovascularization are known causes of treatment resistance in glioblastoma multiforme(GBM). The purpose of this study was to determine the effect of radiation on the growth characteristics of primary human GBM developed in a nude rat. Primary GBM cells grown from explanted GBM tissues were implanted orthotopically in nude rats. Tumor growth was confirmed by magnetic resonance imaging on day 77(baseline) after implantation. The rats underwent irradiation to a dose of 50 Gy delivered subcuratively on day 84 postimplantation(n = 8), or underwent no radiation(n = 8). Brain tissues were obtained on day 112(nonirradiated) or day 133(irradiated). Immunohistochemistry was performed to determine tumor cell proliferation(Ki-67) and to assess the expression of infiltration marker(matrix metalloproteinase-2, MMP-2) and cell migration marker(CD44). Tumor neovascularization was assessed by microvessel density using von-Willebrand factor(vWF) staining. Magnetic resonance imaging showed well-developed, infiltrative tumors in 11 weeks postimplantation. The proportion of Ki-67-positive cells in tumors undergoing radiation was(71 ± 15)% compared with(25 ± 12)% in the nonirradiated group(P = 0.02). The number of MMP-2-positive areas and proportion of CD44-positive cells were also high in tumors receiving radiation, indicating great invasion and infiltration. Microvessel density analysis did not show a significant difference between nonirradiated and irradiated tumors. Taken together, we found that subcurative radiation significantly increased proliferation, invasion, and migration of primary GBM. Our study provides insights into possible mechanisms of treatment resistance following radiation therapy for GBM.

Estimation of Hourly and Daily Global Solar Radiation at Clear Days Using an Approach Based on Modified Version of Gaussian Distribution

The performance of two models,Jam and Baig,based on the modified version of Gaussian distribution function in estimating the daily total of global solar radiation and its distribution through the hours of the day from sunrise to sunset al any clear day is evaluated with our own measured data in the period from June 1992 to May 1993 in Qena Egypt The results show a high relative deviation of calculated values from measured ones,especially for Jain model,in the most hours of the day,except for those near to local noon.This misfit behavior is quite obvious in the early morning and late afternoon A new approach has been proposed in this paper to estimate the daily and hourly global solar radiation This model performs with very high accuracy on the recorded data in our region.The validity of this approach was verified with new measurements in some clear days in June and August 1994.The resultant very low relative deviation of the calculated values of global solar radiation from the measured ones confirms the high performance of the approach proposed in this work