Predictors of post-treatment stenosis in cervical esophageal cancer undergoing high-dose radiotherapy

AIM To evaluate toxicity and treatment outcome of highdose radiotherapy(RT) for cervical esophageal cancer(CEC).METHODS We reviewed a total of 62 consecutive patients who received definitive RT for stage Ⅰ to Ⅲ cervical esophageal cancer between 2001 and 2015. Patients who received < 45 Gy, treated for lesions below sternal notch, treated with palliative aim, treated with subsequent surgical resection, or diagnosed with synchronous hypopharyngeal cancer were excluded. Treatment failures were divided into local(occurring within the RT field), outfield-esophageal, and regional [occurring in regional lymph node(s)] failures. Factors predictive of esophageal stenosis requiring endoscopic dilation were analyzed.RESULTS Grade 1, 2, and 3 esophagitis occurred in 19(30.6%), 39(62.9%), and 4 patients(6.5%), respectively, without grade ≥ 4 toxicities. Sixteen patients(25.8%) developed post-RT stenosis, of which 7 cases(43.8%) were malignant. Four patients(6.5%) developed tracheoesophageal fistula(TEF), of which 3(75%) cases were malignant. Factors significantly correlated with post-RT stenosis were stage T3/4(P = 0.001), complete circumference involvement(P < 0.0001), stenosis at diagnosis(P = 0.024), and endoscopic complete response(P = 0.017) in univariate analysis, while complete circumference involvement was significant in multivariate analysis(P = 0.003). A higher dose(≥ 60 Gy) was not associated with occurrence of postRT stenosis or TEF. With a median follow-up of 24.3(range, 3.4-152) mo, the 2 y local control, outfield esophageal control, progression-free survival, and overall survival(OS) rates were 78.9%, 90.2%, 49.6%, and 57.3%, respectively. Factors significantly correlated with OS were complete circumference involvement(P = 0.023), stenosis at diagnosis(P < 0.0001), and occurrence of post-RT stenosis or TEF(P < 0.001) in univariate analysis, while stenosis at diagnosis(P = 0.004) and occurrence of post-RT stenosis or TEF(P = 0.023) were significant in multivariate analysis. CONCLUSION Chemoradiation for CEC was well tolerated, and a higher dose was not associated with stenosis. Patients with complete circumferential involvement require close follow-up.

Predictability and Management of OARs Toxicity in Patients with Prostate Cancer Treated with High-Dose Radiotherapy

Aim: To evaluate the predictability of toxicity analyzing the dose-volume histograms (DVHs) and to verify the effectiveness of preventive measures limiting side toxicity considering the evolution of the radiation techniques for prostate cancer treatment. Materials and Methods: 208 patients with localized prostate cancer were treated with exclusive radiotherapy until 73.8 Gy (group A) or 79.2 Gy (group B) with the dose escalation technique. Preventive measures to minimize the side effects were recommended in group B. Results: The assessment of genitourinary toxicity was similar while gastrointestinal toxicity was better in group B. Valuating the treatment plans, we found that most of the patients developing toxicity had “borderline” DVHs. Conclusion: Our analysis led to the establishment of a protocol for the management of patients with “border-line” DVH.

Effects of high-dose glucose-insulin-potassium on acute coronary syndrome patients receiving reperfusion therapy:a meta-analysis

BACKGROUND:This meta-analysis aimed to assess the efficacy of high-dose glucose-insulinpotassium(GIK) therapy on clinical outcomes in acute coronary syndrome(ACS) patients receiving reperfusion therapy.METHODS:We searched the PubMed,Web of Science,MEDLINE,Embase,and Cochrane Library databases from inception to April 26,2022,for randomized controlled trials(RCTs) that compared high-dose GIK and placebos in ACS patients receiving reperfusion therapy.The primary endpoint was major adverse cardiovascular events(MACEs).RESULTS:Eleven RCTs with 884 patients were ultimately included.Compared with placebos,high-dose GIK markedly reduced MACEs(risk ratio [RR] 0.57,95% confidence interval [95% CI]:0.35 to 0.94,P=0.03) and the risk of heart failure(RR 0.48,95% CI:0.25 to 0.95,P=0.04) and improved the left ventricular ejection fraction(LVEF)(mean difference [MD] 2.12,95% CI:0.40 to 3.92,P=0.02) at 6 months.However,no difference was observed in all-cause mortality at 30 d or 1 year.Additionally,high-dose GIK was significantly associated with increased incidences of phlebitis(RR 4.78,95% CI:1.36 to 16.76,P=0.01),hyperglycemia(RR 9.06,95% CI:1.74 to 47.29,P=0.009) and hypoglycemia(RR 6.50,95% CI:1.28 to 33.01,P=0.02) but not reinfarction,hyperkalemia or secondary reperfusion.In terms of oxidative stress-lowering function,high-dose GIK markedly reduced superoxide dismutase(SOD) activity but not glutathione peroxidase(GSH-Px) or catalase(CAT) activity.CONCLUSION:Patients with ACS receiving reperfusion therapy exhibited a reduction in MACEs and good oxidative stress-lowering eflcacy in response to high-dose GIK.Moreover,with a higher incidence of complications such as phlebitis,hyperglycemia,and hypoglycemia.Furthermore,there were no observed survival benefits associated with high-dose GIK.More trials with long-term follow-up are still needed.

High-dose methotrexate and zanubrutinib combination therapy for primary central nervous system lymphoma

In this editorial I comment on the article,published in the current issue of the World Journal of Clinical Oncology.Primary central nervous system lymphoma(PCNSL)is a disease of elderly and immunocompromised patients.The authors reported clinical results of 19 patients with PCNSL treated with zanubrutinib/high dose methotrexate(HD-MTX)until disease progression.They demonstrated that the combination of zanubrutinib with HD-MTX led to a marked clinical response and tolerability among these patients.They also observed that cerebrospinal fluid liquid biopsy to detect circulating tumor DNA may be a good option for evaluating treatment response and tumor burden in patients with PCNSL.PCNSL is a challenging disease for treatment as these patients present with different neurological states and comorbidities.Treatment has evolved over the years from whole brain radiotherapy to HD-MTX followed by autologous stem cell transplant.Gradually,treatment of patients with PCNSL is going to become individualized.

Stereotactic body radiotherapy in pancreatic adenocarcinoma

Background:Stereotactic body radiotherapy(SBRT)in pancreatic cancer allows high delivery of radiation doses on tumors without affecting surrounding tissue.This review aimed at the SBRT application in the treatment of pancreatic cancer.Data sources:We retrieved articles published in MEDLINE/PubMed from January 2017 to December 2022.Keywords used in the search included:“pancreatic adenocarcinoma”OR“pancreatic cancer”AND“stereotactic ablative radiotherapy(SABR)”OR“stereotactic body radiotherapy(SBRT)”OR“chemoradiotherapy(CRT)”.English language articles with information on technical characteristics,doses and fractionation,indications,recurrence patterns,local control and toxicities of SBRT in pancreatic tumors were included.All articles were assessed for validity and relevant content.Results:Optimal doses and fractionation have not yet been defined.However,SBRT could be the standard treatment in patients with pancreatic adenocarcinoma in addition to CRT.Furthermore,the combination of SBRT with chemotherapy may have additive or synergic effect on pancreatic adenocarcinoma.Conclusions:SBRT is an effective modality for patients with pancreatic cancer,supported by clinical practice guidelines as it has demonstrated good tolerance and good disease control.SBRT opens a possibility of improving outcomes for these patients,both in neoadjuvant treatment and with radical intent.

Hemostatic radiotherapy for bleeding gastrointestinal

Hemostatic radiotherapy is a non-invasive treatment for bleeding gastrointestinal(GI)tumors,promoting tumor shrinkage,blood supply reduction,and fibrotic tissue formation.It is effective in cases where traditional interventions are insufficient or contraindicated and can prevent recurrent bleeding in patients with GI bleeding histories.Hypofractionation schedules are also effective for tumor control and patient compliance.

Signal intensity changes of dentate nucleus on plain MR T1WI innasopharyngeal carcinoma patients after radiotherapy andmultiple injections of gadolinium-base contrast agent

Objective To observe changes of plain MR T1WI signal intensity of dentate nucleus in nasopharyngeal carcinoma patients after radiotherapy and multiple times of intravenous injection of gadolinium-based contrast agent(GBCA).Methods Fifty patients with pathologically confirmed nasopharyngeal carcinoma and received intensity-modulated radiotherapy were retrospectively enrolled as the nasopharyngeal carcinoma group,and 50 patients with other malignant tumors and without history of brain radiotherapy were retrospectively enrolled as the control group.All patients received yearly GBCA enhanced MR examinations for the nasopharynx or the head.T1WI signal intensities of the dentate nucleus and the pons on same plane were measured based on images in the year of confirmed diagnosis(recorded as the first year)and in the second to the fifth years.T1WI signal intensity ratio of year i(ranging from 1 to 5)was calculated with values of dentate nucleus divided by values of the pons(ΔSI i),while the percentage of relative changes of year j(ranging from 2 to 5)was calculated withΔSI j compared toΔSI 1(Rchange j).The values of these two parameters were compared,and the correlation ofΔSI and GBCA injection year-time was evaluated within each group.Results No significant difference of gender,age norΔSI 1 was found between groups(all P>0.05).The second to the fifth yearΔSI and Rchange in nasopharyngeal carcinoma group were all higher than those in control group(all P<0.05).Within both groups,ΔSI was positively correlated with GBCA injection year-time(both P<0.05).Conclusion Patients with nasopharyngeal carcinoma who underwent radiotherapy and multiple times of intravenous injection of GBCA tended to be found with gradually worsening GBCA deposition in dentate nucleus,for which radiotherapy might be a risk factor.

Present situation and prospect of immunotherapy for unresectable locally advanced esophageal cancer during peri-radiotherapy

Four major studies(Checkmate577,Keynote-590,Checkmate649 and Attraction-4)of locally advanced esophageal cancer published in 2020 have established the importance of immunotherapy,represented by anti-programmed death protein(PD)-1 in postoperative adjuvant treatment and advanced first-line treatment of locally advanced or advanced esophageal cancer and esophagogastric junction cancer,from the aspects of proof of concept,long-term survival,overall survival rate and progression-free survival.For unresectable or inoperable nonmetastatic esophageal cancer,concurrent radiotherapy and chemotherapy is the standard treatment recommended by various guidelines.Because its curative effect is still not ideal,it is necessary to explore radical radiotherapy and chemotherapy in the future,and it is considered to be promising to combine them with immunotherapeutic drugs such as anti-PD-1.This paper mainly discusses how to combine radical concurrent radiotherapy and chemotherapy with immunotherapy for unresectable local advanced esophageal cancer.

Targeting the organelle for radiosensitization in cancer radiotherapy

Radiotherapy is a well-established cytotoxic therapy for local solid cancers, utilizing high-energy ionizing radiation to destroy cancer cells. However, this method has several limitations, including low radiation energy deposition, severe damage to surrounding normal cells, and high tumor resistance to radiation. Among various radiotherapy methods, boron neutron capture therapy (BNCT) has emerged as a principal approach to improve the therapeutic ratio of malignancies and reduce lethality to surrounding normal tissue, but it remains deficient in terms of insufficient boron accumulation as well as short retention time, which limits the curative effect. Recently, a series of radiosensitizers that can selectively accumulate in specific organelles of cancer cells have been developed to precisely target radiotherapy, thereby reducing side effects of normal tissue damage, overcoming radioresistance, and improving radiosensitivity. In this review, we mainly focus on the field of nanomedicine-based cancer radiotherapy and discuss the organelle-targeted radiosensitizers, specifically including nucleus, mitochondria, endoplasmic reticulum and lysosomes. Furthermore, the organelle-targeted boron carriers used in BNCT are particularly presented. Through demonstrating recent developments in organelle-targeted radiosensitization, we hope to provide insight into the design of organelle-targeted radiosensitizers for clinical cancer treatment.

Preliminary Result of Hyperfractionated High-Dose Proton Beam Radiotherapy for Pediatric Skull Base Chordomas

Objective: Proton beam therapy (PBT) may provide good local control for skull base chordoma and reduced toxicities, especially for pediatric patients. Methods: We evaluated the efficacy and safety of hyperfractionated high-dose PBT in6 pediatric patients with newly-diagnosed skull basechordoma who were treated with PBT at our institute from 2011 to 2015. The patients were 5 males and one female, and the median age was 9 years old (range: 5 - 13). All patients received surgery before PBT. The median period between surgery and PBT was 57 days (range: 34 - 129 days). The treatment dose was 78.4 GyE in 56 fractions (twice per day). Results: All patients received PBT without severe acute toxicity. The median follow-up period was 27 months (range: 21 - 71 months). At the last follow-up, all patients were alive and all tumors were well controlled. Acute and late toxicities were generally acceptable, with only grade 1 and 2 events. Late toxicities included growth hormone abnormality and cortical hormone abnormality. One patient needed growth hormone and cortical hormone replacement therapy. Conclusion: Although the number of pediatric patients was small, our overall findings in the 6 cases indicate that hyperfractionated high-dose PBT is safe and effective for pediatric patients with skull base chordoma.

Enhancing Precision in Radiotherapy Delivery: Validating Monte Carlo Simulation Models for 6 MV Elekta Synergy Agility LINAC Photon Beam Using Two Models of the GAMOS Code

The most crucial requirement in radiation therapy treatment planning is a fast and accurate treatment planning system that minimizes damage to healthy tissues surrounding cancer cells. The use of Monte Carlo toolkits has become indispensable for research aimed at precisely determining the dose in radiotherapy. Among the numerous algorithms developed in recent years, the GAMOS code, which utilizes the Geant4 toolkit for Monte Carlo simula-tions, incorporates various electromagnetic physics models and multiple scattering models for simulating particle interactions with matter. This makes it a valuable tool for dose calculations in medical applications and throughout the patient’s volume. The aim of this present work aims to vali-date the GAMOS code for the simulation of a 6 MV photon-beam output from the Elekta Synergy Agility linear accelerator. The simulation involves mod-eling the major components of the accelerator head and the interactions of the radiation beam with a homogeneous water phantom and particle information was collected following the modeling of the phase space. This space was po-sitioned under the X and Y jaws, utilizing three electromagnetic physics mod-els of the GAMOS code: Standard, Penelope, and Low-Energy, along with three multiple scattering models: Goudsmit-Saunderson, Urban, and Wentzel-VI. The obtained phase space file was used as a particle source to simulate dose distributions (depth-dose and dose profile) for field sizes of 5 × 5 cm2 and 10 × 10 cm2 at depths of 10 cm and 20 cm in a water phantom, with a source-surface distance (SSD) of 90 cm from the target. We compared the three electromagnetic physics models and the three multiple scattering mod-els of the GAMOS code to experimental results. Validation of our results was performed using the gamma index, with an acceptability criterion of 3% for the dose difference (DD) and 3 mm for the distance-to-agreement (DTA). We achieved agreements of 94% and 96%, respectively, between simulation and experimentation for the three electromagnetic physics models and three mul-tiple scattering models, for field sizes of 5 × 5 cm2 and 10 × 10 cm2 for depth-dose curves. For dose profile curves, a good agreement of 100% was found between simulation and experimentation for the three electromagnetic physics models, as well as for the three multiple scattering models for a field size of 5 × 5 cm2 at 10 cm and 20 cm depths. For a field size of 10 × 10 cm2, the Penelope model dominated with 98% for 10 cm, along with the three multiple scattering models. The Penelope model and the Standard model, along with the three multiple scattering models, dominated with 100% for 20 cm. Our study, which compared these different GAMOS code models, can be crucial for enhancing the accuracy and quality of radiotherapy, contributing to more effective patient treatment. Our research compares various electro-magnetic physics models and multiple scattering models with experimental measurements, enabling us to choose the models that produce the most reli-able results, thereby directly impacting the quality of simulations. This en-hances confidence in using these models for treatment planning. Our re-search consistently contributes to the progress of Monte Carlo simulation techniques in radiation therapy, enriching the scientific literature.

Radiotherapy for hyoid bone metastasis from lung adenocarcinoma:A case report

BACKGROUND Metastasis to the hyoid bone is an exceptionally rare occurrence,with documented cases limited to breast,liver,colon,skin,lung,and prostate cancers.This report highlights an unusual case involving the metastasis of lung adenocarcinoma to the hyoid bone,accompanied by a distinctive headache.Previous documentation involved surgical resection of the hyoid mass.We present a case displaying the benefits of palliative radiotherapy.CASE SUMMARY A 72-year-old non-smoking,non-alcoholic woman,initially under investigation for a year-long elevation in absolute lymphocyte count,presented with a monthlong history of intermittent throat pain.Despite negative findings in gastroenterological and otolaryngologic examinations,a contrast-enhanced chest computed tomography scan revealed a mediastinal mass and questionable soft tissue thickening in her left anterolateral neck.Subsequent imaging and biopsies confirmed the presence of lung adenocarcinoma metastasis to the hyoid bone.The patient was treated with platinum-based chemo-immunotherapy along with pembrolizumab.Ultimately,the lung cancer was unresponsive.Our patient opted for palliative radiation therapy instead of surgical resection to address her throat pain.As a result,her throat pain was alleviated,and it also incidentally resolved her chronic headaches.This is the second documented case of lung adenocarcinoma metastasizing to the hyoid bone.CONCLUSION Palliative radiotherapy may add to the quality of life in symptomatic patients with cancer metastatic to the hyoid bone.

Chemotherapy and radiotherapy:Could they contribute to the development of new tumors and metastases?

Objective: Both chemotherapy and radiotherapy have demonstrated high effectiveness as the best mechanisms in the fight against cancer;however, various studies seem to confirm that they could also favor the development of other unwanted effects of great importance for the patient. The main objective of this study is to find out the possible existence of this type of links. Method: This is a systematic literature review that seeks to find out which and how long cases of late interactions related to chemotherapy and radiotherapy treatments have been known. The bibliographic review was carried out based on references published in the last five years. Results: Various studies confirm the possible relationship between chemotherapy and radiotherapy treatments with the development of new undesirable side effects, especially as a consequence of the hepatotoxicity generated in the case of chemotherapy and radiation in radiotherapy. However, in this last type of treatment, the problems raised are really few. Conclusions: The existence of a risk of suffering new unwanted side effects after different types of treatment seems to have been demonstrated, especially in the case of chemotherapy. In the case of radiotherapy, adverse effects are practically non-existent, although they are no less important.

Changes in acute and late toxicity and patient-reported health-related quality of life following radiotherapy in women with breast cancer:A 1-year longitudinal study

Objective:The objective of this study was to investigate the frequency of acute and late toxicities,as well as changes in the quality of life(QOL)for breast cancer patients following radiotherapy(RT).Materials and Methods:A total of 108 breast cancer women were recruited for this prospective study.Data were collected at various intervals;prior to,and 1,3,6 months,and 1 year after radiation therapy.The primary outcomes were toxicity radiation therapy oncology group/European Organization for Research and Treatment of Cancer(EORTC)criteria.Our secondary outcome was QOL,measured using EORTC QLQ-C30 and Edmonton Symptom Assessment Scale.We employed Friedman’s two-way analysis to evaluate the changes in QOL over the course of 1 year.Results:The early toxicities that are most commonly experienced include pharyngeal,skin,and mucous membrane toxicity.Late toxicities frequently involve skin and submucosal toxicity.To measure patient functionality,all functional subscale scores except for the patient’s emotional state increased over time compared to pre-RT.Symptoms of the patients,which were included in the QOL symptom scale,decreased during the follow-up period,except for fatigue;however,changes in pain,insomnia,and loss of appetite did not significantly change.We identified the analogous symptom profiles in Edmonton.Although patients’overall health scores declined in the 1st and 3rd months after radiotherapy(RT),they rebounded at 6 and 12 months.Conclusion:For breast cancer patients,RT did not adversely affect functional capacity or exacerbate symptoms,but persistent fatigue did increase during the observation period.Health-care professionals ought to devise strategies to assist patients with skin toxicity and fatigue.

Assessment of Occupational Radiation Exposure for Radiotherapy Healthcare Workers at Kenyatta National Hospital Using Thermoluminescence Dosimeter LiF:Mg,Ti

Kenyatta National Hospital (KNH) is the largest public referral hospital with a comprehensive cancer treatment facility in East and Central Africa. Occupational radiation monitoring is a significant technique for demonstrating compliance of radiation regulatory limits. The objective of the study was to carry out assessment of occupational radiation exposure among radiotherapy personnel at KNH using thermoluminescence dosimeter, TLD. KNH staff were monitored using dosimeter type TLD-100 made of LiF:Mg,Ti, on monthly basis. The reader system used for analysis was Harshaw 8800. The measurement established the average monthly accumulated occupational personnel dose for KNH to be 0.21 mSv and 0.29 mSv for Hp (10) and Hp (0.07) respectively. The accumulated dose results were within the maximum acceptable dose of 1.67 mSv/month and 41.6 mSv/month for Hp (10) and Hp (0.07) respectively. The investigation results were higher than the acceptable public limit of 0.08 mSv/month. Moreover, incidences were noted where the fetus dose limit 0.42 was also exceeded. Evaluation of statistical dose exposure among doctors, nurses and radiographers’ measurement results were within ±0.02 mSv. The study established the average KNH occupational radiation exposure levels for both Hp (10) and Hp (0.07) were within the ICRU recommendation, validating radiation protection safe practice. Data analysis of healthcare workers did not indicate exposure trend biased to any healthcare profession. Hence radiation risk cut across all professional categories. It is recommended that Radiation Monitoring program be reviewed to include non-clinical staff who access the facility. Radiation reporting should not be limited to one facility, but reflect cases where workers are involved in multiple multiple jobs.

Study on the Impact of Post-Mastectomy Radiotherapy on Immediate Breast Reconstruction and Complications: A Meta-Analysis

Background and objective:Immediate breast reconstruction not only reduces the number of surgeries for patients after mastectomy but also decreases psychological and physical trauma,making it increasingly popular.However,there is currently no consensus on the integration of post-mastectomy radiotherapy(PMRT)with reconstruction techniques.This review evaluates the impact of PMRT on complications following immediate breast reconstruction,providing guidance for clinical treatment decisions.Methods:PubMed,Web of Science,Embase,and other databases were searched for studies published in the past 15 years on outcomes of implant-based breast reconstruction in the context of radiotherapy to identify articles for analysis.RevMan 5.4 software was used to analyze the risks of seroma,infection,wound dehiscence,flap necrosis,implant exposure,capsule contracture,and reconstruction failure.Results:A total of 1l relevant studies were included,comprising 6323 cases of immediate breast reconstruction.It was found that breasts receiving postoperative irradiation had a significantly increased risk of complications,with statistically significant differences in seroma(P=0.004),infection(P<0.00001),wound dehiscence(P=0.04),implant exposure(P<0.00001),capsule contracture(P<0.00001),and reconstruction failure(P<0.00001).There was no statistically significant difference in flap necrosis(P=0.88).Conclusion:The results indicate that postoperative radiotherapy significantly increases the risk of complications for patients undergoing immediate implant-based reconstruction.Preventive measures may be taken in advance with the assistance of healthcare providers if necessary.

High-dose vs low-dose proton pump inhibitors for upper gastrointestinal bleeding:A meta-analysis

AIM:To evaluate the efficacy of high-dose proton pump inhibitors(PPIs)vs low-dose PPIs for patients with upper gastrointestinal bleeding.METHODS:PubMed,Embase,the Cochrane Library,and Web of Science were searched to identify relevant randomized controlled trials(RCTs).Eligible trials were RCTs that compared high-dose PPI with low-dose PPI following endoscopic hemostasis.The primary endpoint was rebleeding;secondary endpoints were patient numbers that needed surgery,and mortality.The meta-analysis was performed with a fixed effects model or random effects model.RESULTS:Nine eligible RCTs including 1342 patients were retrieved.The results showed that high-dose intravenous PPI was not superior to low-dose intra-venous PPI in reducing rebleeding[odds ratio(OR)= 1.091,95%confidential interval(CI):0.777-1.532],need for surgery(OR=1.522,95%CI:0.643-3.605) and mortality(OR=1.022,95%CI:0.476-2.196).Subgroup analysis according to different region revealed no difference in rebleeding rate between Asian patients(OR=0.831,95%CI,0.467-1.480)and European patients(OR=1.263,95%CI:0.827-1.929).CONCLUSION:Low-dose intravenous PPI can achieve the same efficacy as high-dose PPI following endoscopic hemostasis.

Establishment of a prediction model for severe acute radiation enteritis associated with cervical cancer radiotherapy

BACKGROUND Cervical cancer is one of the most common gynecological malignant tumors.Radiation enteritis(RE)leads to radiotherapy intolerance or termination of radiotherapy,which negatively impacts the therapeutic effect and seriously affects the quality of life of patients.If the incidence of RE in patients can be predicted in advance,and targeted clinical preventive treatment can be carried out,the side effects of radiotherapy in cervical cancer patients can be significantly reduced.Furthermore,accurate prediction of RE is essential for the selection of individualized radiation dose and the optimization of the radiotherapy plan.AIM To analyze the relationships between severe acute RE(SARE)of cervical cancer radiotherapy and clinical factors and dose-volume parameters retrospectively.METHODS We included 50 cervical cancer patients who received volumetric modulated arc therapy(VMAT)from September 2017 to June 2018 in the Department of Radiotherapy at The First Affiliated Hospital Soochow University.Clinical and dose-volume histogram factors of patients were collected.Logistic regression analysis was used to evaluate the predictive value of each factor for SARE.A nomogram to predict SARE was developed(SARE scoring system≥3 points)based on the multiple regression coefficients;validity was verified by an internal verification method.RESULTS Gastrointestinal and hematological toxicity of cervical cancer VMAT gradually increased with radiotherapy and reached the peak at the end of radiotherapy.The main adverse reactions were diarrhea,abdominal pain,colitis,anal swelling,and blood in the stool.There was no significant difference in the incidence of gastrointestinal toxicity between the radical and postoperative adjuvant radiotherapy groups(P>0.05).There were significant differences in the small intestine V_(20),V_(30),V_(40),and rectal V40 between adjuvant radiotherapy and radical radiotherapy after surgery(P<0.05).Univariate and multivariate analyses revealed anal bulge rating(OR:14.779,95%CI:1.281-170.547,P=0.031)and disease activity index(DAI)score(OR:53.928,95%CI:3.822-760.948,P=0.003)as independent predictors of SARE.CONCLUSION Anal bulge rating(>0.500 grade)and DAI score(>2.165 points)can predict SARE.The nomogram shows potential value in clinical practice.

Dose-volume parameters and clinical outcome of CT-guided free-hand high-dose-rate interstitial brachytherapy for cervical cancer

Currently, image-based 3-dimentional (3D) planning brachytherapy allows for a better assessment of gross tumor volume (GTV) and the definition and delineation of target volume in cervix cancer. In this study, we investigated the feasibility of our novel computed tomography (CT)-guided free-hand high-dose- rate interstitial brachytherapy (HDRISBT) technique for cervical cancer by evaluating the dosimetry and preliminary clinical outcome of this approach. Dose-volume histogram (DVH) parameters were analyzed according to the Gynecological GEC-ESTRO Working Group recommendations for image-based 3D treatment in cervical cancer. Twenty cervical cancer patients who underwent CT-guided free-hand HDRISBT between March 2009 and June 2010 were studied. With a median of 5 (range, 4-7) implanted needles for each patient, the median dose of brachytherapy alone delivered to 90% of the target volume (D90 ) was 45 (range, 33-54) Gyα/β10 for high-risk clinical target volume (HR-CTV) and 30 (range, 20-36) Gyα/β10 for intermediate-risk clinical target volume (IR-CTV). The percentage of the CTV covered by the prescribed dose (V100 ) of HR-CTV with brachytherapy alone was 81.9%-99.2% (median, 96.7%). With an additional dose of external beam radiotherapy (EBRT), the median D90 was 94 (range, 83-104) Gyα/β10 for HR-CTV and 77 (range, 70 -87) Gyα/β10 for IR-CTV; the median dose delivered to 100% of the target volume (D100 ) was 75 (range, 66-84) Gyα/β10 for HR-CTV and 65 (range, 57-73) Gyα/β10 for IR-CTV. The minimum dose to the most irradiated 2 cc volume (D2cc ) was 73-96 (median, 83) Gyα/β3 for the bladder, 64-98 (median, 73) Gyα/β3 for the rectum, and 52-69 (median, 61) Gyα/β3 for the sigmoid colon. After a median follow-up of 15 months (range, 3 -24 months), two patients experienced local failure, and 1 showed internal iliac nodal metastasis. Despite the relatively small number of needles used, CT-guided HDRISBT for cervical cancer showed favorable DVH parameters and clinical outcome.

Implications of recent neoadjuvant clinical trials on the future practice of radiotherapy in locally advanced rectal cancer

Over the last two decades, the standard treatment for locally advanced rectal cancer(LARC) has been neoadjuvant chemoradiotherapy plus total mesorectal excision followed by adjuvant chemotherapy. Total neoadjuvant treatment(TNT) and immunotherapy are two major issues in the treatment of LARC. In the two latest phase Ⅲ randomized controlled trials(RAPIDO and PRODIGE23), the TNT approach achieved higher rates of pathologic complete response and distant metastasis-free survival than conventional chemoradiotherapy. Phase I/II clinical trials have reported promising response rates to neoadjuvant(chemo)-radiotherapy combined with immunotherapy. Accordingly, the treatment paradigm for LARC is shifting toward methods that increase the oncologic outcomes and organ preservation rate. However, despite the progress of these combined modality treatment strategies for LARC, the radiotherapy details in clinical trials have not changed significantly. To guide future radiotherapy for LARC with clinical and radiobiological evidence, this study reviewed recent neoadjuvant clinical trials evaluating TNT and immunotherapy from a radiation oncologist’s perspective.