Different types of tumor microvessels in stageⅠ-ⅢA squamous cell lung cancer and their clinical significance

BACKGROUND Lung cancer(LC)is the leading cause of morbidity and mortality among malignant neoplasms.Improving the diagnosis and treatment of LC remains an urgent task of modern oncology.Previously,we established that in gastric,breast and cervical cancer,tumor microvessels(MVs)differ in morphology and have different prognostic significance.The connection between different types of tumor MVs and the progression of LC is not well understood.AIM To evaluate the morphological features and clinical significance of tumor MVs in lung squamous cell carcinoma(LUSC).METHODS A single-center retrospective cohort study examined medical records and archival paraffin blocks of 62 and 180 patients with stage I-IIIA LUSC in the training and main cohorts,respectively.All patients underwent radical surgery(R0)at the Orenburg Regional Cancer Clinic from May/20/2009 to December/14/2021.Tumor sections were routinely processed,and routine Mayer's hematoxylin and eosin staining and immunohistochemical staining for cluster of differentiation 34(CD34),podoplanin,Snail and hypoxia-inducible factor-1 alpha were performed.The morphological features of different types of tumor MVs,tumor parenchyma and stroma were studied according to clinicopathological characteristics and LUSC prognosis.Statistical analysis was performed using Statistica 10.0 software.Univariate and multivariate logistic regression analyses were performed to identify potential risk factors for LUSC metastasis to regional lymph nodes(RLNs)and disease recurrence.Receiver operating characteristic curves were constructed to discriminate between patients with and without metastases in RLNs and those with and without disease recurrence.The effectiveness of the predictive models was assessed by the area under the curve.Survival was analyzed using the Kaplan-Meier method.The log-rank test was used to compare survival curves between patient subgroups.A value of P<0.05 was considered to indicate statistical significance.RESULTS Depending on the morphology,we classified tumor vessels into the following types:normal MVs,dilated capillaries(DCs),atypical DCs,DCs with weak expression of CD34,"contact-type"DCs,structures with partial endothelial linings,capillaries in the tumor solid component and lymphatic vessels in lymphoid and polymorphocellular infiltrates.We also evaluated the presence of loose,fine fibrous connective tissue(LFFCT)and retraction clefts in the tumor stroma,tumor spread into the alveolar air spaces(AASs)and fragmentation of the tumor solid component.According to multivariate analysis,the independent predictors of LUSC metastasis in RLNs were central tumor location(P<0.00001),the presence of retraction clefts(P=0.003),capillaries in the tumor solid component(P=0.023)and fragmentation in the tumor solid component(P=0.009),whereas the independent predictors of LUSC recurrence were tumor grade 3(G3)(P=0.001),stage N2(P=0.016),the presence of LFFCT in the tumor stroma(P<0.00001),fragmentation of the tumor solid component(P=0.0001),and the absence of tumor spread through the AASs(P=0.0083).CONCLUSION The results obtained confirm the correctness of our previously proposed classification of different types of tumor vessels and may contribute to improving the diagnosis and treatment of LUSC.

Predictors of disease recurrence after radical resection and adjuvant chemotherapy in patients with stage IIb-IIIa squamous cell lung cancer:A retrospective analysis

BACKGROUND Lung cancer(LC)is a global medical,social and economic problem and is one of the most common cancers and the leading cause of mortality from malignant neoplasms.LC is characterized by an aggressive course,and in the presence of disease recurrence risk factors,patients,even at an early stage,may be indicated for adjuvant therapy to improve survival.However,combined treatment does not always guarantee a favorable prognosis.In this regard,establishing predictors of LC recurrence is highly important both for determining the optimal treatment plan for the patients and for evaluating its effectiveness.AIM To establish predictors of disease recurrence after radical resection and adjuvant chemotherapy in patients with stage IIb-IIIa lung squamous cell carcinoma(LSCC).METHODS A retrospective case-control cohort study included 69 patients with LSCC who underwent radical surgery at the Orenburg Regional Clinical Oncology Center from 2009 to 2018.Postoperatively,all patients received adjuvant chemotherapy.Histological samples of the resected lung were stained with Mayer's hematoxylin and eosin and examined under a light microscope.Univariate and multivariate analyses were used to identify predictors associated with the risk of disease recurrence.Receiver operating characteristic curves were constructed to discriminate between patients with a high risk of disease recurrence and those with a low risk of disease recurrence.Survival was analyzed using the Kaplan-Meier method.The log-rank test was used to compare survival curves between patient subgroups.Differences were considered to be significant at P<0.05.RESULTS The following predictors of a high risk of disease recurrence in patients with stage IIb-IIa LSCC were established:a low degree of tumor differentiation[odds ratio(OR)=7.94,95%CI=1.08-135.81,P=0.049];metastases in regional lymph nodes(OR=5.67,95%CI=1.09-36.54,P=0.048);the presence of loose,fine-fiber connective tissue in the tumor stroma(OR=21.70,95%CI=4.27-110.38,P=0.0002);and fragmentation of the tumor solid component(OR=2.53,95%CI=1.01-12.23,P=0.049).The area under the curve of the predictive model was 0.846(95%CI=0.73-0.96,P<0.0001).The sensitivity,accuracy and specificity of the method were 91.8%,86.9%and 75.0%,respectively.In the group of patients with a low risk of LSCC recurrence,the 1-,2-and 5-year disease-free survival(DFS)rates were 84.2%,84.2%and 75.8%,respectively,while in the group with a high risk of LSCC recurrence the DFS rates were 71.7%,40.1%and 8.2%,respectively(P<0.00001).Accordingly,in the first group of patients,the 1-,2-and 5-year overall survival(OS)rates were 94.7%,82.5%and 82.5%,respectively,while in the second group of patients,the OS rates were 89.8%,80.1%and 10.3%,respectively(P<0.00001).CONCLUSION The developed method allows us to identify a group of patients at high risk of disease recurrence and to adjust to ongoing treatment.

IgG4 Coronary Arteritis Presenting as a Cardiac Pseudo-Tumour

We report on an unusual case presenting with a cardiac pseudo-tumour on echocardiogram, which corresponded to a large soft tissue mural thickening around the mid-right coronary artery. There were similar but not as thick mural lesions around other parts of the coronary arteries. The so-called “pigs-in-a-blanket” sign on computed tomography (CT) scan was pathognomonic of IgG4 coronary arteritis. The IgG4 level was grossly elevated at more than 10 times the upper limit of normal. Positron emission tomography (PET)-CT scans with 18F-fluoro-deoxy-glucose (FDG) and 68Ga-Fibroblast Activation Protein Inhibitor (FAPI) were performed to assess the extent of organ involvement of the IgG4-related disease. The patient was treated with 8 injections of rituximab with good serological response. However, the coronary arteritis findings on CT scan remained unchanged.

Prescription of Cancer Treatment Modalities in Developing Countries:Results from a Multi-Centre Observational Study

Background: Treatment is an important component of a comprehensive cancer control approach and its outcomes strongly depend on infrastructure, equipment, human and financial resources available. Therefore it is imperative to generate evidence-based tools to assist health policy makers from low resourced countries in planning efficient and equitable treatment services for a defined population based on what it is feasible to these settings. Methods: The intended cancer spe-cific treatment planned and written in the patients’ medical record (treatment prescription) of untreated adult cancer cases (≥18 years of age), excluding non-melanoma skin cancer, was recorded in a chronological way from 1 January 2012 onwards in a group of eight comprehensive cancer centres located in middle income countries and offering the main modalities of cancer treatment (surgery, medical oncology and radiotherapy). Results: A total of 17,713 medical records were reviewed, of which 7106 (54.2%) met the eligibility criteria. Prescription of main cancer treatment modalities were distributed as follows: 57.6% for chemotherapy (n = 4093), 56.8% for surgery (n = 4038), and 46.8% for radiotherapy (n = 3327). There was a predominance of plans consisting of combined treatment modalities over monotherapy (55.2% versus 44.8%). At the time of diagnosis 54.3% of the cancer cases had disease that had spread beyond the primary site, 41.2% were considered as having local disease and in 4.5% of the cases the information on disease extension was unknown. Conclusions: The results obtained should be seen as an approximation of cancer treatment service demand based on what it is currently practiced and therefore feasible in developing countries, particularly in middle income countries.

Role of pulmonary perfusion magnetic resonance imaging for the diagnosis of pulmonary hypertension:A review

Among five types of pulmonary hypertension,chronic thromboembolic pulmonary hypertension(CTEPH)is the only curable form,but prompt and accurate diagnosis can be challenging.Computed tomography and nuclear medicine-based techniques are standard imaging modalities to non-invasively diagnose CTEPH,however these are limited by radiation exposure,subjective qualitative bias,and lack of cardiac functional assessment.This review aims to assess the methodology,diagnostic accuracy of pulmonary perfusion imaging in the current literature and discuss its advantages,limitations and future research scope.

己酮可可碱对嘧啶拮抗物细胞毒性的影响

目的:观察己酮可可碱(pentoxifylline,PTX)在体外对嘧啶拮抗物(E)-(2')-脱氧-氟亚甲基胞苷犤(E)-2'-deoxy-2'-(fluoromethylene)cytidine,FMdC犦和5-氟尿嘧啶(5-fluorouracil,5-FU)细胞毒性的影响。方法:用MTT法检测PTX和FMdC或5-FU对人结肠癌细胞系WiDr的细胞毒性。用流式细胞仪检测FMdC和PTX的细胞周期效应。结果:0.25-2.0mmol/LPTX增加FMdC和5-FU的细胞毒性。2mmol/LPTX能使FMdC的半数抑制浓度(IC50)从80nmol/L降到24nmol/L;对5-FU的IC50从10μmol/L降到1.1μmol/L。Isoborogram分析表明,PTX和FMdC或5-FU的细胞毒性作用为相乘作用。在WiDr细胞,20-40nmol/LFMdC引起S期阻滞,并与浓度相关。20nmol/LFMdC时,S期阻滞仅在48h能观察到;30nmol/L和40nmol/LFMdC时,12h开始出现S期阻滞,24h达高峰,48h仍可见明显阻滞。0.5-2.0mmol/LPTX和30nmol/LFMdC共同处理细胞24h,PTX能去除FMdC引起的S期阻滞。0.5mmol/L和1.0mmol/LPTX将S期比例从64.6%分别减少到54.4%和39.3%。结论:PTX能增强体外FMdC和5-FU的细胞毒性,通过PTX去除S期阻滞,为提高嘧啶拮抗物的细胞毒性提供了一种有效途径。

Metastatic gastric cancer treatment: Second line and beyond

Advanced gastric cancer(a GC), not amenable to curative surgery, is still a burdensome illness tormenting afflicted patients and their healthcare providers. Whereas combination chemotherapy has been shown to improve survival and tumor related symptoms in the frontline setting, second-line therapy(SLT) is subject to much debate in the scientific community, mainly because of the debilitating effects of GC, which would impede the administration of cytotoxic therapy. Recent data has provided sufficient evidence for the safe use of SLT in patients with an adequate performance status. Taxanes, Irinotecan and even some Fluoropyrimidine analogs were found to provide a survival advantage in this subset of patients. Most importantly, quality of life measures were also improved through the use of adequate therapy. Even more pertinent were the findings involving antiangiogenic agents, which would add measurable improvements without significantly jeopardizing the patients' well-being. Further lines of therapy are cause for much more debate nowadays, but specific targeted agents have shown considerable promise in this context. We herein review noteworthy published data involving the use of additional lines of the therapy after failure of standard frontline therapies in patients with a GC.

欧洲肿瘤内科协会对非上皮性卵巢癌的诊断、治疗和随访所制定的临床实践指南

非上皮性卵巢癌是一类少见的卵巢癌,因此,其诊断较难建立。然而,通过仔细观察各种肿瘤的标记物[尤其是人绒毛膜促性腺激素β亚单位（β-hCG）、α-甲胎蛋白（α-AFP）和乳酸脱氢酶（LDH）]、临床体征（如妊娠期体征,

How to assess the efficacy or failure of targeted therapy:deciding when to stop sorafenib in hepatocellular carcinoma

Sorafenib is thus far the only systemic treatment for hepatocellular carcinoma(HCC) based on the results of two randomized controlled trials performed in Western and in Eastern countries, despite a poor response rate(from 2% to 3.3%) following conventional evaluation criteria. It is now recognized that the criteria(European Association of the Study of the Liver criteria, modified response evaluation criteria in solid tumors) based on contrast enhanced techniques(computed tomography scan, magnetic resonance imaging) aimed to assess the evolution of the viable part of the tumor(hypervascularized on arterial phase) are of major interest to determine the efficacy of sorafenib and of most antiangiogenic drugs in patients with HCC. The role of alphafetoprotein serum levels remains unclear. In 2016, in accordance with the SHARP and the Asia-Pacific trials, sorafenib must be stopped when tolerance is poor despite dose adaptation or in cases of radiological and symptomatic progression. This approach will be different in cases of available second-line therapy trials. Some recent data(in renal cell carcinoma) revealed that despite progression in patients who received sorafenib, this drug can still decrease tumor progression compared to drug cessation. Then, before deciding to continue sorafenib post-progression or shift to another drug, knowing other parameters of post-progression survival(Child-Pugh class, Barcelona Clinic Liver Cancer, alphafetoprotein, post-progression patterns in particular, the development of extrahepatic metastases and of portal vein thrombosis) will be of major importance.

Outcomes of preoperative chemoradiotherapy followed by surgery in patients with unresectable locally advanced sigmoid colon cancer

Background: Complete resection of locally advanced sigmoid colon cancer(LASCC) is sometimes difficult. Patients with LASCC have a dismal prognosis and poor quality of life, which has encouraged the evaluation of alternative multimodality treatments. This prospective study aimed to assess the feasibility and efficacy of neoadjuvant chemora?diotherapy(neo CRT) followed by surgery as treatment of selected patients with unresectable LASCC.Methods: We studied the patients with unresectable LASCC who received neo CRT followed by surgery between October 2010 and December 2012. The neoadjuvant regimen consisted of external?beam radiotherapy to 50 Gy and capecitabine?based chemotherapy every 3 weeks. Surgery was scheduled 6–8 weeks after radiotherapy.Results: Twenty?one patients were included in this study. The median follow?up was 42 months(range, 17–57 months). All patients completed neo CRT and surgery. Resection with microscopically negative margins(R0 resection) was achieved in 20 patients(95.2%). Pathologic complete response was observed in 8 patients(38.1%). Multivisceral resection was necessary in only 7 patients(33.3%). Two patients(9.5%) experienced grade 2 postopera?tive complications. No patients died within 30 days after surgery. For 18 patients with pathologic M0(yp M0) disease, the cumulative probability of 3?year local recurrence?free survival, disease?free survival and overall survival was 100.0%, 88.9% and 100.0%, respectively. For all 21 patients, the cumulative probability of 3?year overall survival was 95.2% and bladder function was well preserved.Conclusion: For patients with unresectable LASCC, preoperative chemoradiotherapy and surgery can be performed safely and may result in an increased survival rate.

Helical tomotherapy and volumetric modulated arc therapy:New therapeutic arms in the breast cancer radiotherapy

AIM To analyse clinical and dosimetric results of helical tomotherapy(HT) and volumetric modulated arc therapy(VMAT) in complex adjuvant breast and nodes irradiation.METHODS Seventy-three patients were included(31 HT and 42 VMAT). Dose were 63.8 Gy(HT) and 63.2 Gy(VMAT) in the tumour bed, 52.2 Gy in the breast, 50.4 Gy in supraclavicular nodes(SCN) and internal mammary chain(IMC) with HT and 52.2 Gy and 49.3 Gy in IMC and SCN with VMAT in 29 fractions. Margins to particle tracking velocimetry were greater in the VMAT cohort(7 mm vs 5 mm).RESULTS For the HT cohort, the coverage of clinical target volumes was as follows: Tumour bed: 99.4% ± 2.4%; breast: 98.4% ± 4.3%; SCN: 99.5% ± 1.2%; IMC:96.5% ± 13.9%. For the VMAT cohort, the coverage was as follows: Tumour bed: 99.7% ± 0.5%, breast: 99.3% ± 0.7%; SCN: 99.6% ± 1.4%; IMC: 99.3% ± 3%. For ipsilateral lung, Dmean and V20 were 13.6 ± 1.2 Gy, 21.1% ± 5%(HT) and 13.6 ± 1.4 Gy, 20.1% ± 3.2%(VMAT). Dmean and V30 of the heart were 7.4 ± 1.4 Gy, 1% ± 1%(HT) and 10.3 ± 4.2 Gy, 2.5% ± 3.9%(VMAT). For controlateral breast Dmean was 3.6 ± 0.2 Gy(HT) and 4.6 ± 0.9 Gy(VMAT). Acute skin toxicity grade 3 was 5% in the two cohorts.CONCLUSION HT and VMAT in complex adjuvant breast irradiation allow a good coverage of target volumes with an acceptable acute tolerance. A longer follow-up is needed to assess the impact of low doses to healthy tissues.

Postoperative change of anti-Thomsen-Friedenreich and Tn IgG level: The follow-up study of gastrointestinal cancer patients

AIM: To study the influence of tumor removal on the serum level of IgG antibodies to tumor-associated Thomsen-Friedenreich (TF), Tn carbohydrate epitopes and xenogeneic αGal, and to elucidate on the change of the level during the follow-up as well as its association with the stage and morphology of the tumor and the values of blood parameters in gastrointestinal cancer. METHODS: Sixty patients with gastric cancer and 34 patients with colorectal cancer in stages Ⅰ-Ⅳ without distant metastases were subjected to follow- up. The level of antibodies in serum was determined by the enzyme-linked immunosorbent assay (ELISA) using synthetic polyacrylamide (PAA) glycoconjugates. Biochemical and haematological analyses were performed using automated equipment. RESULTS: In gastrointestinal cancer, the TF antibody level was found to have elevated significantly after the removal of G3 tumors as compared with the preoperative level (u = 278.5, P < 0.05). After surgery, the TF and Tn antibody level was elevated in the majority of gastric cancer patients (sign test, 20 vs 8, P < 0.05, and 21 vs 8, P < 0.05, respectively). In gastrointestinal cancer, the elevated postoperative level of TF, Tn and αGal antibodies was noted in most patients with G3 tumors (sign test, 22 vs 5, P < 0.01; 19 vs 6, P < 0.05; 24 vs 8, P < 0.01, respectively), but the elevation was not significant in patients with G1 + G2 resected tumors. The postoperative follow-up showed that the percentage of patients with G3 resected tumors of the digestive tract, who had a mean level of anti-TF IgG above the cut- off value (1.53), was significantly higher than that of patients with G1 + G2 resected tumors (χ2 = 3.89, all patients; χ2 = 5.34, patients without regional lymph node metastases; P < 0.05). The percentage of patients with a tumor in stage I, whose mean anti-TF IgG level remained above the cut-off value (1.26), was significantly higher than that of patients with the cancer in stages Ⅲ-Ⅳ (χ2 = 4.71, gastric cancer; χ2 = 4.11, gastrointestinal cancer; P < 0.05). The correlation was observed to exist between the level of anti-TF IgG and the count of lymphocytes (r = 0.517, P < 0.01), as well as between the level of anti- Tn IgG and that of serum CA 19-9 (r = 0.481, P < 0.05). No positive delayed-type hypersensitivity reaction in skin test challenges with TF-PAA in any of the fifteen patients, including those with a high level of anti-TF IgG, was observed. CONCLUSION: The surgical operation raises the level of anti-carbohydrate IgG in most patients, especially in those with the G3 tumor of the gastrointestinal tract. The follow-up demonstrates that after surgery the low preoperative level of TF antibodies may be considerably increased in patients with the carcinoma in its early stage but remains low in its terminal stages. The stage- and morphology-dependent immunosuppression affects the TF-antibody response and may be one of the reasons for unresponsiveness to the immunization with TF-antigens.

Risk factors and natural history of breast cancer in younger Chinese women

AIM: To investigate the age differences in the risk factors, clinicopathological characteristics and patterns of treatment of female breast cancer patients. METHODS: Seven thousand one hundred and fiftytwo women with primary breast cancer from the Hong Kong Breast Cancer Registry were recruited after receiving patients' consent, they were asked to complete standardized questionnaires which captured their sociodemographic characteristics and risk factors associated with breast cancer development. Among them, clinicopathological data and patterns of treatment were further collected from medical records of 5523 patients with invasive breast cancers. Patients were divided into two groups according to the age at diagnosis: younger(< 40 years old) vs older patients(≥ 40 years old) for subsequent analyses.RESULTS: Analysis on the sociodemographic characteristics and exposure to risk factors were performed on 7152 women with primary breast cancer and the results revealed that younger patients were more likely to have unhealthy lifestyles; these include a lack of exercise(85.4% vs 73.2%, P < 0.001), having high stress in life(46.1% vs 35.5%, P < 0.001), having dairy/meat-rich diets(20.2% vs 12.9%, P < 0.001),having alcohol drinking habit(7.7% vs 5.2%, P = 0.002). Younger patients were also more likely to have hormone-related risk factors including nulliparity(43.3% vs 17.8%, P < 0.001) and an early age at menarche(20.7% vs 13.2%, P < 0.001). Analyses on clinicopathological characteristics and patterns of treatment were performed on 5523 women diagnosed with invasive breast cancer. The invasive tumours in younger patients showed more aggressive pathological features such as having a higher percentage of grade 3 histology(45.7% vs 36.5%, P < 0.001), having a higher proportion of tumours with lymphovascular invasion(39.6% vs 33.2%, P = 0.003), and having multifocal disease(15.7% vs 10.3%, P < 0.001); they received different patterns of treatment than their older counterparts.CONCLUSION: Younger patients in Hong Kong are more likely to encounter risk factors associated with breast cancer development and have more aggressive tumours than their older counterparts.

FOLFIRI plus bevacizumab as a second-line therapy for metastatic intrahepatic cholangiocarcinoma

AIM:To evaluate the efficacy and tolerance of FOLFIRI plus bevacizumab treatment outcome as second-line treatment for metastatic intrahepatic cholangiocarcinoma.METHODS:Thirteen consecutive patients with metastatic intrahepatic cholangiocarcinoma who were refractory tofirst-line therapy consisting of gemcitabine plus oxaliplatinbased first-line chemotherapy given intravenously via intra-arterial infusion were treated with FOLFIRI[irinotecan(180 mg/m2 i.v.over 90 min)concurrently with folinic acid(400 mg/m2 i.v.over 120 min)followed by fluorouracil(400 mg/m2 i.v.bolus)then fluorouracil 2400 mg/m2 intravenous infusion over 46 h]and bevacizumab(5mg/kg)every 2 wk.Tumor response was evaluated by computed tomography scan every 4 cycles.RESULTS:The best tumor responses using response evaluation criteria in solid tumor criteria were:complete response for 1 patient,partial response for 4 patients,and stable disease for 6 patients after 6 mo of follow-up.The response rate was 38.4%(95%CI:12.5-89)and the disease control rate was 84.5%(95%CI:42-100).Seven deaths occurred at the time of analysis,progression free survival was 8 mo(95%CI:7-16),and median overall survival was 20 mo(95%CI:8-48).No grade 4toxic events were observed.Four grade 3 hematological toxicities and one grade 3 digestive toxicity occurred.An adaptive reduction in chemotherapy dosage was required in 2 patients due to hematological toxicity,and a delay in chemotherapy cycles was required for 3 patients.CONCLUSION:FOLFIRI plus bevacizumab combination treatment showed promising efficacy and safety as second-line treatment for metastatic intrahepatic cholangiocarcinoma after failure of the first-line treatment of gemcitabine plus oxaliplatin chemotherapy.

Retrospective evaluation of FOLFIRI3 alone or in combination with bevacizumab or aflibercept in metastatic colorectal cancer

BACKGROUND The treatment of metastatic colorectal cancer(mCRC) relies of chemotherapy. The efficacy of the standard FOLFIRI-therapy could be improved by a modification of the regimen by splitting the dose of irinotecan on day 1 and day 3 in the FOLFIRI3 regimen.AIM To determine safety and efficacy of FOLFIRI3 regimen.METHODS This is a monocentric retrospective study evaluating the efficacy and safety of the FOLFIRI3 regimen given alone or in combination with bevacizumab or aflibercept in patients with previously treated mCRC.RESULTS One hundred and fifty-three consecutive patients were included(18 treated with FOLFIRI3, 99 with FOLFIRI3 plus bevacizumab and 36 with FOLFIRI3 plus aflibercept). The overall response rate(ORR) and disease control rate were 51%and 62%, respectively. Similar ORRs were observed in all 3 cohorts. Median progression-free survival(PFS) and overall survival(OS) were 3.9 mo(95%CI:3.2-4.9) and 9.4 mo(95%CI: 6.6-12), respectively. Median PFS and OS values were improved in the FOLFIRI3 plus aflibercept group. The most common grade 3-4 adverse events were diarrhoea(21.6%) and neutropenia(11.8%), and these toxicities were more frequent in the FOLFIRI3 plus aflibercept group. According to the multivariate Cox proportional model, previous surgery of metastasis andaflibercept were associated with outcomes.CONCLUSION The modification of the FOLFIRI regimen impacted treatment response of mCRC patients. The addition of an antiangiogenic agent, in particular aflibercept,enhanced the clinical benefit and improved survival.

Folfirinox in elderly patients with pancreatic or colorectal cancer-tolerance and efficacy

AIM To study the tolerance and the efficiency of FOLFIRINOX in elderly patients diagnosed with colorectal or pancreatic cancer.METHODS This retrospective study included elderly patients aged over 70 years of age treated at Georges-Francois Leclerc Center by FOLFIRINOX for histological proved colorectal or pancreatic cancer between January 2009 and January 2015. Chemotheapy regimen consisted of oxaliplatin(85 mg/m2 in over 120 min) followed by leucovorin(400 mg/m2 in over 120 min), with the addition, after 30 min of irinotecan(180 mg/m2 in over 90 min) then 5 fluorouracil(5FU)(400 mg/m2 administred intravenous bolus), followed by 5FU(2400 mg/m2 intraveinous infusion over 46 h) repeated every 2 wk. Geriatric parameters were recorded at the beginning. Toxicities were evaluated with the Common Terminology Criteria for Adverse Events 4.03. Tumor response was evaluated by CT scan. Treatment continued until disease progression, unacceptable toxicities or patient refusal.RESULTS Fifty-two patients aged from 70 to 87 years were treated by FOLFIRINOX, 34 had colorectal cancer and 18 had pancreatic cancer. Most of them were in good general condition, 82.7% had a 0-1 performance status and 61.5% had a Charlson Comorbidity Index < 10. The most frequent severe toxicities were neutropenia(17 patients, n = 32.7%) and diarrhea(35 patients n = 67.3%); 10 of the case of neutropenia and 5 of diarrhea registered a grade 4 toxicity. Thirty-nine patients(75%) initially received an adapted dose of chemotherapy. The dosage was adjusted for 26% of patients during the course of treatment. Tumor response evaluated by RECIST criteria showed a controlled disease for 25 patients(48.1%), a stable disease for 13 and a partial response for 12 patients. Time under treatment was higher for colorectal cancer with a median time of 2.44 mo(95%CI: 1.61-3.25). Overall survival was 43.88 mo for colorectal cancer and 12.51 mo for pancreatic cancer. In univariate or multivariate analysis, none of geriatric parameters were linked to overall survival. Only the type of tumor(pancreatic/colorectal) was linked in both analysis.CONCLUSION For people over 70 years old, FOLFIRINOX regimen seems to induce manageable toxicities but similar, even higher, median survival rates compared to younger people.

Systemic chemotherapy for hepatocellular carcinoma in non-cirrhotic liver:A retrospective study

AIM:To investigate the efficacy and toxicity of systemic chemotherapy in a retrospective study of patients with hepatocellular carcinoma(HCC)occurring in normal or fibrotic liver without cirrhosis. METHODS:Twenty-four patients with metastatic or locally advanced HCC in a normal or a fibrotic liver were given systemic chemotherapy(epirubicin,cis- platin and 5-fluorouracil or epirubicin,cisplatin and capecitabine regimens).Tumor response,time to pro- gression,survival,and toxicity were evaluated. RESULTS:There were 7 women and 17 men,mean age 54±10 years;18 patients had a normal liver and 6 had a fibrotic liver(F1/F2 on biopsy).Mean tumor size was 14 cm,5 patients had portal vein thrombosis and 7 had metastasis.Patients received a median of 4 chemotherapy sessions.Overall tolerance was good. There were 5 partial responses(objective response rate =22%),and tumor control rate was 52%.Second line surgical resection was possible in two patients.Median survival was 11 mo,and 1-and 2-year overall survival rates were 50%±10%and 32%±11%,respectively. CONCLUSION:In patients with HCC in a non-cirrhotic liver,chemotherapy was well tolerated and associated with an objective response rate of 22%,including two patients who underwent secondary surgical resection.

Potential of mRNA vaccines to become versatile cancer vaccines

For centuries,therapeutic cancer vaccines have been developed and tried clinically.Way back in the late 19th century,the Father of Immunotherapy,William Coley had discovered that bacterial toxins were effective for inoperable sarcomas.In the 1970s,the Bacillus Calmette-Guérin(BCG)vaccine was repurposed,e.g.,for advanced melanomas.Then,therapeutic cancer vaccines based on tumorassociated antigens(found on the surfaces of cancer cells)were tried clinically but apparently have not made a really significant clinical impact.For repurposed pathogen vaccines,only the BCG vaccine was approved in 1989 for local application to treat nonmuscle-invading bladder cancers.Although the mildly toxic vaccine adjuvants deliberately added to conventional pathogen vaccines are appropriate for seasonal applications,when repurposed for continual oncology usage,toxicity may be problematic.In 2010,even with the approval of sipuleucel-T as the very first cancer vaccine(dendritic cell)developed for designated prostate cancers,it has also not made a really significant clinical impact.Perhaps more"user friendly"cancer vaccines should be explored.As from approximately 30 years ago,the safety and effectiveness of mRNA vaccination for oncology had already been studied,the current coronavirus disease 2019 pandemic,though disastrous,has given such progressively advancing technology a kickstart.For oncology,other virtues of mRNA vaccines seem advantageous,e.g.,rapid and versatile development,convenient modular design,and entirely cell-free synthesis,are being progressively recognized.Moreover,mRNAs encoding various oncology antigens for vaccination may also be tested with the combination of relatively non-toxic modalities of oncology treatments,e.g.,metformin or metronomic(low-dose,prolonged administration)chemotherapy.Admittedly,robust clinical data obtained through good quality clinical trials are mandatory.

Prognostic value of chemotherapy-induced hematological toxicity in metastatic colorectal cancer patients

AIM: To establish whether chemotherapy-induced neutropenia is predictive of better outcome in patients with metastatic colorectal cancer (mCRC).

Intensity-modulated radiotherapy for breast cancer:a systematic review

Objective:The aim of this study was to assess the long-term effect of breast conservation with breast intensitymodulated radiotherapy (IMRT) for early-stage breast cancers.Methods:Pub Med,EMBASE,Cochrane Library,Chinese Biomedical Literature Database were searched to identify relevant original published trails,and the references of eligible studies were manually screened.Randomized controlled trails reported in any language,comparing breast IMRT with conventional radiotherapy (RT) in patients with early-stage breast cancer were eligible for inclusion.Two investigators independently assessed the quality of included trials and extracted data.The RevMan 5.0 software was used for statistical analysis.Results:Four trials involving 1440 patients were included.The results showed that in the IMRT group,the occurrence of acute moist dermatitis,the edema of the mammary gland and the occurrence of hyperpigmentation were lower than those of RT group,the pooled risk ratio value and 95% confidence interval were 0.28 (0.17-0.48),0.03 (0.00-0.21) and 0.06 (0.02-0.15) respectively.The use of IMRT did not correlate with pain and quality of life,but the presence of moist desquamation did significantly correlate with pain and reduced quality of life.Conclusion:The currently available evidence showed that IMRT significantly reduces the occurrence of moist acute dermatitis anywhere in the breast and alleviates the suffering of patients and improves the quality of life of patients.Future large-scale,high-quality,double-blind trials are needed.