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.

Hypofractionated and intensity-modulated radiotherapy combined with systemic therapy in metastatic hepatocellular carcinoma:A case report

BACKGROUND Liver cancer treatment is characterized by multidisciplinary participation and coexistence of multiple treatment methods.Hypofractionated and intensity-modulated radiotherapy is a new precise radiotherapy technique applied to the treatment of systemic malignant tumors.There is a lack of understanding of hypofractionated and intensity-modulated radiotherapy combined with systemic therapy in metastatic hepatocellular carcinoma(HCC).CASE SUMMARY We report a case of metastatic HCC treated with hypofractionated and intensity-modulated radiotherapy combined with systemic therapy.A 41-year-old man was diagnosed with metastatic HCC(T3N1M1 stage IVB).Because it was found to be in the late stage of cancer and had already metastasized,it was impossible to undergo surgical treatment.In addition to aggressive comprehensive treatment for the primary lesion,local treatment for metastatic cancer can improve the patient's survival potential.Hypofractionated and intensity-modulated radiotherapy can provide a larger single treatment dose within a shorter overall treatment time,and improve the local control rate of the tumor.Follow-up examination demonstrated that the tumor and metastatic lesions had shrunk after therapy.The treatment has showed good efficacy.The patient survived for 18 months without disease progression and stable disease persisted for>38 months.CONCLUSION Targeted therapy and immunotherapy followed by hypofractionated and intensity-modulated radiotherapy are also effective for advanced metastatic HCC.

Hypofractionated radiotherapy in the treatment of early breast cancer

Radiotherapy(RT) after tumorectomy in early breast cancer patients is an established treatment modality which conventionally takes 6-7 wk to complete.Shorter RT schedules have been tested in large multicentre randomized trials and have shown equivalent results to that of standard RT(50 Gy in 25 fractions) in terms of local tumor control,patient survival and late post-radiation effects.Some of those trials have now completed 10 years of follow-up with encouraging results for treatments of 3-4 wk and a total RT dose to the breast of 40-42.5 Gy with or without boost.A reduction of 50% in treatment time makes those RT schedules attractive for both patients and health care providers and would have a significant impact on daily RT practice around the world,as it would accelerate patient turnover and save health care resources.However,in hypofractionated RT,a higher(than the conventional 1.8-2 Gy) dose per fraction is given and should be managed with caution as it could result in a higher rate of late postradiation effects in breast,heart,lungs and the brachial plexus.It is therefore advisable that both possible dose inhomogeneity and normal tissue protection should be taken into account and the appropriate technology such as three-dimensional/intensity modulated radiation therapy employed in clinical practice,when hypofractionation is used.

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.

Concurrent use of aromatase inhibitors and hypofractionated radiation therapy

AIM: To retrospectively assess the acute and long-term toxicity using aromatase inhibitors (AI) therapy concurrently with hypofractionated radiotherapy (HFRT) in breast cancer patients. METHODS: From November 1999 to October 2007, 66 patients were treated with breast HFRT and concurrent AI. In 63 patients (95.5%), HFRT delivered a total dose of 32.5 Gy to the whole breast within 5 wk (five fractions, one fraction per week). Other fractionations were chosen in three patients for the patients' personal convenience. A subsequent boost to the tumor bed was delivered in 35 patients (53.0%). Acute toxicities were scored according to the Common Toxicity Criteria for Adverse Events v3. Late toxicity was defined as any toxicity occurring more than 6 mo after completion of HFRT and was scored according to the Late Effects Normal Tissue Task Force-Subjective, Objective, Management and Analytic scale. RESULTS: At the end of the HFRT course, 19 patients (28.8%) had no irradiation-related toxicity. Acute grade 1-2 epithelitis was observed in 46 patients (69.7%). One grade 3 toxicity (1.5%) was observed. With a median follow-up of 34 mo (range: 12-94 mo), 31 patients (47%) had no toxicity, and 35 patients (53%) presented with grade 1-2 fibrosis. No grade 3 or greater delayed toxicity was observed. CONCLUSION: We found that AI was well tolerated when given concurrently with HFRT. All toxicities were mild to moderate, and no treatment disruption was necessary. Further prospective assessment is warranted.

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.

Adjuvant chemotherapy and acute toxicity in hypofractionated radiotherapy for early breast cancer

AIM: To evaluate the effect of chemotherapy to the acute toxicity of a hypofractionated radiotherapy(HFRT) schedule for breast cancer. METHODS: We retrospectively analyzed 116 breast cancer patients with T1, 2N0 Mx. The patients received3-D conformal radiotherapy with a total physical dose of 50.54 Gy or 53.2 Gy in 19 or 20 fractions according to stage, over 23-24 d. The last three to four fractions were delivered as a sequential tumor boost. All patients were monitored for acute skin toxicity according to the European Organization for Research and Treatment of Cancer/Radiation Therapy Oncology Group criteria. The maximum monitored value was taken as the final grading score. Multivariate analysis was performed for the contribution of age, chemotherapy and 19 vs 20 fractions to the radiation acute skin toxicity.RESULTS: The acute radiation induced skin toxicity was as following: grade Ⅰ 27.6%, grade Ⅱ 7.8% and grade Ⅲ 2.6%. No significant correlation was noted between toxicity grading and chemotherapy(P = 0.154, χ2 test). The mean values of acute toxicity score in terms of chemotherapy or not, were 0.64 and 0.46 respectively(P = 0.109, Mann Whitney test). No significant correlation was also noted between acute skin toxicity and radiotherapy fractions(P = 0.47, χ2test). According to univariate analysis, only chemotherapy contributed significantly to the development of acute skin toxicity but with a critical value of P = 0.05. However, in multivariate analysis, chemotherapy lost its statistical significance. None of the patients during the 2-years of follow-up presented any locoregional relapse.CONCLUSION: There is no clear evidence that chemotherapy has an impact to acute skin toxicity after an HFRT schedule. A randomized trial is needed for definite conclusions.

The Effect of Hypofractionated Radiotherapy on Tumor Control and Survival in Patients with High-Risk Breast Cancer

BACKGROUND Adjuvant radiotherapy is given following surgery in breast cancer patients. Hypofractonated radiotherapy can significantly reduce the waiting time for radiotherapy, working load on machines, patient visits to radiotherapy departments and medical costs. Material and Methods 244 patients with high-risk breast cancer (stage IIB, stage III and stage IA with any of the following criteria: lymphovascular invasion, hormonal receptor negative, young age) who underwent Breast conservative surgery (BCS) or Modified radical mastectomy (MRM) were enrolled in this study. All patients received adjuvant radiotherapy with different hypofractionation schedules either 3900 cGY/13 fractions or 4240 cGY/16 fractions or 4005 cGY/15 fractions using linear accelerator with 6 MV photon beam. Lateral/Medial tangential and Ipsilateral supraclavicular fields were employed and the ipsilateral axilla was also irradiated if required to the same dose with posteroanterior field. Patients were followed every 3 mons for the first 2 years and every 6 mons thereafter. Outcomes were analyzed in terms of tumor control and survival. Results 244 patients with high-risk breast cancer requiring postoperative radiotherapy to the intact breast or chest wall were treated. The mean age was 48 years (range 28 - 69 years). The 5-year locoregional free survival of all patients was 93.8% the local relapse reported in 15 patients (6.2%) 7 patients at site of operated scar & 8 patients at the regional lymph nodes. The median follow up period was 75 months ranged from 49 to 102 months. Distant metastasis free survival was 92.2%, the distant metastasis reported in 19 patients which represent (7.8%) of all patients, median survival is 75 months ranged from 49 to 102 months and overall survival was 88.6%. Conclusion It is concluded that hypofractionated radiotherapy is a simple and effective protocol in patients with high-risk breast cancer regarding tumor control and survival.

Intensity Modulated Radiotherapy (IMRT) in the Planning of Hypofractionated Treatment in Head and Neck Tumors

Head and neck cancer (HNCC) is the sixth most common cancer with an incidence of approximately 600,000 cases per year and 300,000 annual deaths worldwide1y2. In Cuba, cancer of the larynx is the fourth cause in incidence, being the fourth cause of cancer death in men. Radiotherapy constitutes an important modality in the control of these tumors and the Intensity Modulated Radiotherapy (IMRT) is a new advance in this field. With it, it is possible to improve dose distribution, decreasing the dose in adjacent healthy tissues and escalating dose in tumor. In this work we present 33 patients of National Institute of Oncology and Radiobiology in Cuba (INOR), in whom the IMRT was used as a treatment technique with a hypofractionation of the dose. Their response was observed at the end of the treatment and one month later. 56% (19) of the patients had a complete response to treatment at the primary site of the tumor and neck. 10% (3) had no response, progressed. 11 of the patients had no response at the lymph node site at the end of treatment, 8 of these 11 had complete remission one month after radiotherapy ended.

Application of biological optimization of hypofractionated radiotherapy post conservative surgery for breast cancer

Objective The aim of the study was to discuss the application of biological optimization and its difference from physical optimization in hypofractionated radiotherapy for breast cancer after conservative surgery.Methods This retrospective study enrolled 15 randomly chosen patients with left-sided breast cancer who received radiotherapy.The volumetric arc therapy(VMAT)technique was used to redesign treatment plans with physical functions(PF)group,biological-physical functions combined(BF+PF and PF+BF)groups,and biological functions(BF)group.The dosimetric differences based on the above four optimization methods were assessed by calculating and analyzing the corresponding dose-volume parameters.Results The target parameters of the four groups differed significantly(P<0.05)except for the conformity index(CI).The tumor control probability(TCP)values in the BF and BF+PF groups were higher than those in the PF and PF+BF groups.Moreover,the dose-volume parameters of the ipsilateral lung in the BF group were less than those of three other groups,while the monitor unit(MU)in the BF group was approximately 16%lower than those of the PF and PF+BF groups.Conclusion Biological functions were useful to increase the equivalent uniform dose(EUD)and TCP values of the target,decrease the dose-volume parameters of the organs-at-risk(OARs),and improve treatment efficiency.

Assessment of contralateral mammary gland dose in the treatment of breast cancer using accelerated hypofractionated radiotherapy

AIM:To measure the dose distribution,related to the treatment planning calculations,in the contralateral mammary gland of breast cancer patients treated with accelerated hypofractionated 3-dimensional conformal radiotherapy.METHODS:Thirty-four prospectively selected female patients with right breast cancer (pN0,negative surgical margins) were treated with breast-conserving surgery.A total dose of 42.5 Gy (2.66 Gy/fraction) was prescribed;it was requested that planning target volumes be covered by the 95% isodose line.The contralateral mam-mary gland was defined on CT simulation.The dose received was evaluated by dose volume histograms.RESULTS:The measured contralateral breast doses were:(1) Dose maximum:290-448 cGy [Equivalent (Eq) 337-522 cGy];(2) Mean dose:45-70 cGy (Eq 524815 cGy);and (3) Median dose:29-47 cGy (337-547 cGy) for total primary breast dose of 42.5 Gy in 16 equal fractions.The spearman rho correlation showed statistical significance between the contralateral breast volume and maximum dose (P=0.0292),as well as mean dose (P=0.0025) and median dose (P=0.046) to the breast.CONCLUSION:Minimizing the dose to the contralateral breast has to be one of the priorities of the radiation oncologist when using short schedules because of the radiosensitivity of this organ at risk.Further study is necessary to assess the long-term clinical impact of this schedule.

Hypofractionated versus Conventionally Fractionated Radiotherapy in Post-Mastectomy Breast Cancer Patients

Background & Objective: Hypofractionation has been used in curative setting in breast conservative surgery, but still no adequate information about its application in the adjuvant setting after mastectomy in breast cancer patients. The aim of this trial was to assess the efficacy and toxicity of hypofractionation radiotherapy (40 Gy in 15 fractions) in post mastectomy breast cancer patients and to compare these results with those of post mastectomy patients treated retrospectively by conventional radiotherapy (50 Gy in 25 fractions) as regard overall survival (OS), disease free survival (DFS), locoregional disease free survival (LDFS), and toxicities. Patients & Methods: One hundred post mastectomy breast cancer patients were included into this study, they were divided into 2 groups, the 1st included 50 patients treated prospectively with hypofractionated radiotherapy regimen (40 Gy in 15 fractions), and the 2nd (control group) included 50 patients treated retrospectively with conventionally fractionated radiotherapy regimen (50 Gy in 25 fractions). Results: The 2 year overall survival were 96% & 94% respectively (p = 0.7), while the disease free survival were 91% & 89.8%, respectively (p = 0.9), and the LDFS were 95.8% & 93.3%, respectively (p = 0.9), G1 acute dermatitis was observed in 22 (44%) & 25 (50%) patients in group I & II respectively, G2 in 8 (16%) & 10 (20%) patients respectively, no G4 skin toxicity was detected. Radiation pneumonitis was observed in 2 patients (4%) only in group II. Conclusion: post-mastectomy hypofractionated radiation therapy achieved comparable survival and toxicity to the conventionally fractionated radiotherapy with the advantage of reducing overall treatment time, treatment burden & cost.

Estimation of the effect of target and normal tissue sparing based on equivalent uniform dose-based optimization in hypofractionated radiotherapy for lung cancer

Objective This study aims to investigate the dosimetric differences among four planning methods of physical and biological optimization in hypofractionated radiation therapy for non-small cell lung cancer(NSCLC).Methods Ten NSCLC patients receiving radiation therapy were chosen for this retrospective study.Volumetric modulated arc treatment plans for each patient were remade with dose-volume(DV)functions,biological-physical functions,and biological functions,using the same constraint parameters during optimization.The dosimetric differences between the four types of plans were calculated and analyzed.Results For the target,equivalent uniform dose(EUD)of the EUD and EUD+DV groups was approximately 2.8%–3.6%and 3.2%–3.7%higher than those of the DV and DV+EUD groups,respectively.The average tumor control probability(TCP)of the EUD and EUD+DV groups was also significantly higher than those of the other two groups(P<0.05).The difference in heterogeneity index(HI)among the four groups was also statistically significant(P<0.05),while the difference of conformity index(CI)was not significant(P>0.05).For the organs at risk,the differences of EUD,V5,V10,V20,V30 of normal lung tissues were not statistically significant(P>0.05);however,the mean lung dose of the EUD and EUD+DV groups was slightly lower than those of the other two groups.Conclusion The biological optimization method has obvious advantages of improving EUD and TCP of the target,while decreasing the exposed dose of normal lung.This result is meaningful in choosing plan optimization methods in routine work.

Hypofractionated Radiotherapy for Stage I Non-small Cell Lung Carcinoma in Patients Aged 75 Years and Older

Purpose: We report our single-institution experience using hypofractionated radiotherapy in a patient population 75 years and older diagnosed with stage IA or IB (T1/T2 N0) Non-Small Cell Lung Carcinoma. Materials and methods: This is a single-institution, retrospective analysis examining disease free and overall survival and toxicity after hypofractionated radiation therapy in a patient population 75 years and older diagnosed with stage IA or IB (T1/T2 N0) NSCLC. Between 1991 and 2005, a total of 33 such patients were identified with a median age of 79 years. Patients were treated with a median total dose of 7000 cGy using median daily dose fractions of 250 cGy. Analysis of competing risks (local failure, distal failure or death as the first event) was performed and cumulative incidence functions (CIF) were estimated. Results: The median length of follow-up was 19.8 months (range: 4.3 - 103.8 months). Of the 33 patients treated, 21 (63.6% of total) had no evidence of disease recurrence on follow-up imaging over the course of the study. Of the 12 patients with disease recurrence, 6 (18.2% of total) had local failure as the first event and 6 (18.2% of total) had distant metastasis as the first event. Analysis of competing risks showed that at 5 years, the probability of local failure as the first detected event was 19.5% (95%CI: 7.6%, 35.6%);the probability of distal failure as the first detected event was 21.5% (95%CI: 7.9%,39.4%);and the probability of death without recording a failure was 44.1% (95%CI: 26.1%, 60.7%). There were no treatment related deaths reported. Conclusions: Elderly patients diagnosed with stage I non-small cell lung cancer may safely be offered hypofractionated radiotherapy as an effective option with curative intent.

Toxicity of Hypofractionated Radiotherapy Following Breast Conservative Surgery in Breast Cancer

Background:Adjuvant radiotherapy has increased disease-free and overall survival rates in breast cancer. Conventionally fractionated radiotherapy delivers 50 Gy over 5 weeks which is the standard approach. A shorter duration of hypofractionated radiotherapy (HFRT) will be more convenient for patients and treatment providers if found safe and equally effective. Material and Methods: Fifty-four breast cancer patients who underwent breast conservative surgery (BCS) were enrolled in this study. The patients received 4005 cGy/15 fractions. A boost to the tumor bed was administered in all patients. In this study, radiotherapy induced toxicity was evaluated. Results: In this study, the median age of our patients was 48 years with age ranged from 28 to 69 years. Acute skin toxicity was assessed, and it was noted that grade 2 skin toxicity was shown in only 6 patients (11.1%) at the end of radiotherapy and disappeared after 6 weeks of treatment. Late skin toxicity (telangectasia, hyperpigmentation, and subcutaneous fibrosis) was assessed and showed that most patients had grade 0 toxicity with no grade 3 toxicity at all. Regarding pulmonary toxicity, 5 patients (9.3%) developed acute pneumonitis and as regards chronic lung toxicity, it was evident in only 3 patients, 2 patients (3.7%) were grade 1 and 1 patient (1.9%) was grade 2. Cardiac toxicity was evident in 2 patients (7.1%) of the left breast cancer patients. Regarding lymphoedema, most patients that showed lymphoedema were grade 1. Conclusion: The results confirm the safety and feasibility of adjuvant hypofractionated whole breast radiotherapy in breast cancer patients in terms of acute and late toxicity.

High-dose interferon-α2b induction therapy in combination with ribavirin for treatment of chronic hepatitis C in patients with non-response or relapse after interferon-a monotherapy

AIM： To evaluate the daily high-dose induction therapy with interferon-α2b （IFN-α2b） in combination with ribavirin for the treatment of patients who failed with interferon monotherapy and had a relapse, based on the assumption that the viral burden would decline faster, thus increasing the likelihood of higher response rates in this difficult-totreat patient group. METHODS： Seventy patients were enrolled in this study. Treatment was started with 10 NU IFN-α2b daily for 3 wk, followed by IFN-α2b 5 NU/TIW in combination with ribavirin （1 000-1 200 mg/d） for 21 wk. In case of a negative HCV RNA PCR, treatment was continued until wk 48 （IFN-α2b 3MU/TIW＋1000-1200 mg ribavirin/daily）. RESULTS： The dose of IFN-α2b or ribavirin was reduced in 16% of patients because of hematologic side effects, and treatment was discontinued in 7% of patients. An early viral response （EVR） was achieved in 60% of patients. Fifty percent of all patients achieved an end-oftreatment response （EOT） and d0% obtained a sustained viral response （SVR）. Patients with no response had a significantly lower response rate than those with a former relapse （SVR 30% vs 53%; P=0.049）. Furthermore, lower response rates were observed in patients infected with genotype la/b than in patients with non-1-genotype （SVR 28% vs7d%; P=0.001）. As a significant predictive factor for a sustained response, a rapid initial decline of HCV RNA could be identified. No patient achieving a negative HCV-RNA PCR at wk 18 or later eventually eliminated the virus. CONCLUSION： Daily high-dose induction therapy with interferon-α2b is well tolerated and effective for the treatment of non-responders and relapsers, when interferon monotherapy fails. A fast decline of viral load during the first 12 wk is strongly associated with a sustained viral response.

Dose-individualization Efficiently Maintains Sufficient Exposure to Methotrexate without Additional Toxicity in High-dose Methotrexate Regimens for Pediatric Acute Lymphoblastic Leukemia

Objective:Methotrexate(MTX)can be safely administered to most patients but may cause severe toxicity in others.This study aimed to summarize the characteristics of high-dose methotrexate(HD-MTX)chemotherapy and to evaluate whether the modified dose-adjustment program was able to improve the maintenance of sufficient MTX exposure levels while minimizing toxicities.Methods:We evaluated 1172 cycles of high-dose MTX chemotherapy from 294 patients who were treated according to the CCCG-ALL-2015 protocol(clinical trial number:ChiCTR-IPR-14005706)and analyzed the data of actual MTX dosage,MTX concentration,toxicity,and prognosis.We compared data between the dose-adjustment Program 1(fixed 20%reduction in dose)and the dose-adjustment Program 2(dose-individualization based on reassessment of the creatine clearance rate and the MTX concentration-monitoring point at 16 h),which were applied if the MTX clearance was delayed in the previous cycle.Results:The patients who used Program 2 had higher actual MTX infusion doses and infusion rates and were able to better maintain the MTX concentration at 44 h at the established target value than those on Program 1(P<0.001).No significant differences in toxicities were found between these two programs except that abnormal serum potassium levels and prolonged myelosuppression in intermediate-risk/high-risk patients were more frequently observed in patients using Program 2(P<0.001).No significant correlations were observed between the MTX dose,dose-adjustment programs,or MTX concentrations and relapse-free survival.Conclusion:Adjusting the MTX dose using Program 2 is more efficient for maintaining sufficient MTX exposure without significantly increasing the toxicity.

Advanced gastric cancer achieving major pathologic regression after chemoimmunotherapy combined with hypofractionated radiotherapy: A case report

BACKGROUND Currently,chemotherapy combined with immunotherapy is the established firstline standard treatment for advanced gastric cancer(GC).In addition,the combination of radiotherapy and immunotherapy is considered a promising treatment strategy.CASE SUMMARY In this report,we present a case of achieving nearly complete remission of highly advanced GC with comprehensive therapies.A 67-year-old male patient was referred to the hospital because he presented with dyspepsia and melena for several days.Based on fluorodeoxyglucose positron emission tomography/computed tomography(FDG PET/CT),endoscopic examination and abdominal CT,he was diagnosed with GC with a massive lesion and two distant metastatic lesions.The patient received mFOLFOX6 regimen chemotherapy,nivolumab and a short course of hypofractionated radiotherapy(4 Gy×6 fractions)targeting the primary lesion.After the completion of these therapies,the tumor and the metastatic lesions showed a partial response.After having this case discussed by a multidisciplinary team,the patient underwent surgery,including total gastrectomy and D2 lymph node dissection.Postoperative pathology showed that major pathological regression of the primary lesion was achieved.Chemoimmuno therapy started four weeks after surgery,and examination was performed every three months.Since surgery,the patient has been stable and healthy with no evidence of recurrence.CONCLUSION The combination of radiotherapy and immunotherapy for GC is worthy of further exploration.

Hypofractionated Radiation Therapy for the Treatment of Breast Cancer: Experience of National Institute of Oncology, Rabat, Morocco

Hypofractionated radiation therapy has proven effective on locoregional control and tolerance in the adjuvant treatment of breast cancer. The aim of this study is to compare the results of hypofractionated radiation therapy versus conventional radiation therapy in terms of local control and tolerance. It was a retrospective study of patients observations collected from January 2007 to December 2008 in Department of Radiation Therapy in Institut National d’Oncologie de Rabat. The treatment results were evaluated by the rate of locoregional recurrence, distant recurrence and research of late toxicities. Radiotherapy was delivered using the same technique in both groups, by gamma photons of cobalt 60 with an energy of 1.25 MeV. They were 2 groups: the first group treated with standard dose rate and the second group treated by hypofractionated radiation therapy. The mean age of the patients was 42.8 ± 6.9 years old in the standard group and 43.22 ± 7.2 years old in the hypofractionation group. We noted a predominance of infiltrating ductal carcinoma. The majority of patients were pT2, pN0 and pN1. The majority of patients had radical surgery and chemotherapy with anthracyclines in both groups. We noted a statistically significant difference in the irradiation of chest wall between the standard (89.2%) and hypofractionated group (70.3%), with p = 0.043. The median duration of radiation therapy was statistically different in both groups: 39 days in the standard and 23 days in the hypofractionated group (p 0.001). The local recurrences were statistically identical to 12 and 24 months (p = 0.999). Concerning toxicities, the frequency of adverse event was similar in both groups. Hypofractionated radiation therapy with a total dose of 42 Gy at 2.8 Gy per fraction in 5 fractions weekly is comparable to standard radiotherapy in terms of local control and tolerance and is therefore a very good alternative to standard treatment.

A Comparative Study of the Recurrence Rate in Hypofractionated versus Conventional Postmastectomy Radiation in Breast Cancer

Background: Treatment options available for breast cancer are Surgery [Breast conservation surgery (BCS) or Modified radical mastectomy (MRM)];Radiation treatment [Conventional radiation treatment or CRT and Hypofractionated radiation treatment or HRT] and Chemotherapy. In the postmastectomy or post lumpectomy setting, radiotherapy (RT) improves loco-regional control. CRT for breast includes 50 Gy in 25 fractions (2 Gy per fraction) and HRT includes 42.5 Gy in 16 fractions (2.7 Gy per fraction) or extreme hypofractionation like 26 Gy in 5 fractions. Alpha/beta value for breast is less, so HRT is ideal for breast. So, there will be good loco-regional control, without increased normal tissue damage. This study aims to identify recurrence rate and toxicity in breast cancer patients treated using conventional and hypofractionated postmastectomy radiotherapy among Indian population. Primary objective: To assess recurrence rate of disease in breast cancer patients treated using hypofractionated postmastectomy radiation and to compare it with breast cancer patients treated using conventional postmastectomy radiation. Secondary objective: To assess the toxicity in hypofractionation and conventional fractionation arm. Methods: This is a prospective observational study conducted in Department of Radiation Oncology from December 2017 to June 2019. Radically treated breast cancer patients who received radiation treatment either conventional or hypofractionated as one of the treatment modalities were included in the study. Data were collected using a structured proforma, history and physical examination, master file of the patients, lab results and the imaging reports, written informed consent form, ECOG performance status scale (Eastern Cooperative Oncology Group), RTOG (Radiation Therapy Oncology Group) Acute Radiation Morbidity Scoring Schema. Patients were monitored for 18 months to identify recurrence rate and toxicity in each arm. Results and discussion: A total of 241 patients were enrolled into this study, among them 175 patients (73%) were given hypofractionation radiotherapy and 66 patients (27%) were given conventional radiotherapy. In hypofractionation arm, recurrence was found in 14 patients (8%), of which, 3 were local recurrences [chest wall] and 11 were systemic recurrences, while in conventional arm, recurrence was found in 4 patients (6%) and all of them were systemic recurrences. Recurrence rate in hypofractionation arm was 8% and in conventional arm was 6.10%. The Kaplan Meier curve shows no significant difference between the two arms with p value = 0.76. Acute toxicities assessed were dermatitis, esophagitis and pneumonitis. Among acute dermatitis, 4 patients had grade 3 and 2 patients had grade 4 in hypofractionation arm, while in conventional arm, 7 patients had grade 3 and 1 patient had grade 4. Grade 1 and 2 together versus grade 3 and 4 acute dermatitis showed a statistically significant difference between the two arms, with more acute toxicity in the conventional arm. Among acute esophagitis, 1 patient had grade 3 and no patients had grade 4 in hypofractionation arm;while in conventional arm, no grade 3 and grade 4 acute esophagitis were found. Among acute pneumonitis, 2 patients had grade 3 and 1 patient had grade 4 in hypofractionation arm, while in conventional arm, 1 patient had grade 3 and no patients with grade 4 were found. Grade 2 and grade 3 acute lung toxicities were found in patients with central lung distance more than 1.5 cm. Conclusion: It was found that the recurrence rate of hypofractionation radiotherapy was comparable to conventional fractionation radiotherapy. With respect to acute dermatitis, grade 1 and grade 2 were significantly more in conventional than hypofractionation arm. Hypofractionated radiotherapy is an equally effective option to conventional radiotherapy and should be encouraged, especially for developing countries like India where the resource is limited, and the incidence of tumour is high.