Emerging melanoma vaccines

No satisfactory treatment currently exists for melanoma once it has spread beyond its original site. At present, the only FDA-approved treatment for advanced melanoma is IFN-α_2b. Vaccines are an experimental therapy intended to stimulate the immune system to react more strongly against patients’ own melanoma cells, thereby destroying the tumour or slowing its progression. Unfortunately, the exact tumour antigens that can stimulate an effective tumour-protective response in humans remain unknown. The approach that is increasingly followed to circumvent this problem is to prepare polyvalent vaccines containing a variety of melanoma antigens, as the greater the number of antigens in a vaccine, the greater the chance it will contain the correct antigen(s) to stimulate an antitumour response. Two recent randomised trials suggest that this approach results in vaccines that can be clinically effective. One is a double-blind, placebo-controlled trial of a polyvalent, shed antigen melanoma vaccine developed by Bystryn and licenced to NeoVac; the other is a larger randomised trial of Melacine^® (Corixa Corp.), a vaccine prepared from the lysate of two melanoma cell lines adjuvanted with Detox?, which was developed by Mitchell and commercialised by Corixa. In both cases, tumour progression was delayed in the vaccine-treated patients, although in the latter trial, this was only observed in patients with certain human leukocyte antigen phenotypes. Several other vaccines are currently in Phase III trials, but the results of these trials are still pending. The major issues that need to be addressed are designing more effective melanoma vaccines with a mix of melanoma-associated antigens that can stimulate clinically beneficial antitumour immune responses, and finding an adjuvant that can safely, easily and powerfully boost the frequency and magnitude of these responses.     

Chemotherapy causes cancer! A case report of therapy related acute myeloid leukaemia in early stage breast cancer.

Use of chemotherapy and radiotherapy in the adjuvant setting has improved survival for many patients with malignancy. Unfortunately multimodality treatment can come at a price, in particular therapy-related malignancies. This has importance in that patients must be made aware of this potential detriment from therapy and doctors must consider this diagnosis in those patients who are cancer survivors and presenting with health problems. We present a case report and brief overview of the literature regarding chemotherapy-induced acute myeloid leukaemia (AML) following therapy for early stage breast cancer.     

Efficacy of extended adjuvant therapy with aromatase inhibitors in early breast cancer among common clinicopathologically-defined subgroups: A systematic review and meta-analysis

BackgroundRandomized controlled trials (RCTs) have shown improvements in breast cancer outcomes from extending treatment with aromatase inhibitors (AIs) beyond the initial 5 years after diagnosis. Consistency of this effect in common clinicopathologically defined subgroups was not been reported systematically.MethodsWe identified RCTs comparing extended AIs to placebo or no treatment using a systematic search of MEDLINE and a review of abstracts from key conferences between 2013 and 2016. Hazard ratios (HRs) and 95% confidence intervals (CI) for disease-free survival (DFS) were included in a meta-analysis using generic inverse variance and random effects modelling. Pre-specified subgroups included: age (<60 ± 5 years versus ≥60 ± 5 years), tumor size (>2 cm versus ≤2 cm), nodal status (positive versus negative), hormone receptor status (double versus single receptor expression) and receipt of adjuvant chemotherapy (yes versus no).ResultsSeven trials comprising 16,349 patients were analyzed. Overall, the effect of extended AIs was similar in all subgroups. Non-significantly greater effect sizes were seen in patients with larger tumors (HR for DFS 0.77 versus 0.88, p for difference = 0.44), nodal involvement (HR = 0.72 versus 0.83, p for difference = 0.22), double hormone receptor expression (HR = 0.68 versus 1.01, p for difference = 0.31) and receipt of adjuvant chemotherapy (HR = 0.71 versus 0.80, p for difference = 0.51).ConclusionsExtended treatment with AIs is associated with similar relative improvements in DFS in all subgroups analyzed. The combination of greater effect size and higher absolute risk of recurrence in node positive and larger tumors will likely translate to higher absolute benefits from extended AIs in these groups.     

Granulocyte‐macrophage colony‐stimulating factor,a potent adjuvant for polarization to Th‐17 pattern: an experience on HIV‐1 vaccine model

Cytokines are mediators for polarization of immune response in vaccines. Studies show that co‐immunization of DNA vaccines with granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) can increase immune responses. Here, experimental mice were immunized with HIV‐1_{tat/pol/gag/env} DNA vaccine with GM‐CSF and boosted with recombinant vaccine. Lymphocyte proliferation with Brdu and CTL activity, IL‐4, IFN‐γ, IL‐17 cytokines, total antibody, and IgG1 and IgG2a isotypes were assessed with ELISA. Results show that GM‐CSF as adjuvant in DNA immunization significantly increased lymphocyte proliferation and IFN‐γ cytokines, but CTL response was tiny increased. Also GM‐CSF as adjuvant decreased IL‐4 cytokine vs mere vaccine group. IL‐17 in the group that immunized with mixture of DNA vaccine/GM‐CSF was significantly increased vs DNA vaccine group. Result of total antibody shows that GM‐CSF increased antibody response in which both IgG1 and IgG2a increased. Overall, results confirmed the beneficial effect of GM‐CSF as adjuvant to increase vaccine immunogenicity. The hallmark result of this study was to increase IL‐17 cytokine with DNA vaccine/GM‐CSF immunized group. This study for the first time provides the evidence of the potency of GM‐CSF in the induction of IL‐17 in response to a vaccine, which is important for control of infection such as HIV‐1.     

膀胱部分切除加髂内动脉化疗治疗老年人浸润性膀胱癌远期随访

目的探讨动脉化疗在老年人浸润性膀胱癌行保留膀胱术后应用的可行性。方法对52例浸润性膀胱癌患者行膀胱部分切除术保留膀胱,同时髂内动脉置化疗泵,术后定期注射化疗药物顺铂（PDD）50 mg及氨甲喋呤（MTX）40 mg,每2周1次,共6次,以后每1个月1次至1年,每3个月1次至3年。结果52例获得6～60个月随访,平均36个月。无复发者36例,有效率69.2%。术后1、2、3、4、5年内分别有4、3、3、2、1例发生局部复发,3例于术后2、3、4年远处转移而死亡。化疗副作用较静脉用药及膀胱腔内灌注明显减轻。结论动脉化疗可以作为老年人浸润性膀胱癌膀胱部分切除术后的辅助治疗,且能保留膀胱功能。     

益气散结法联合 mFOLFOX6术后辅助化疗治疗Ⅲ期结肠癌的临床研究

目的：观察益气散结法联合 mFOLFOX6术后辅助化疗对Ⅲ期结肠癌的治疗作用。方法将80例病理分期为Ⅲ期的结肠癌术后患者随机分为对照组与治疗组,每组40例。对照组单纯行 mFOLFOX6术后辅助化疗,治疗组口服散结益气法中药联合化疗治疗。观察两组病例的1年后生活质量评分、3年无病生存率（DFS）、5年生存时间及化疗毒副作用的发生率。结果1年后两组生存质量评分治疗组高于对照组（P ﹤0.05）。两组3年 DFS 与5年平均生存时间比较,治疗组均较对照组延长,但差异无统计学意义（P ﹥0.05）。治疗过程中治疗组的白细胞减少、胃肠道反应和周围神经毒性反应发生率明显低于对照组（P ﹤0.05）。结论益气散结法联合化疗治疗结肠癌能部分减低化疗药物的不良反应,对提高患者生存质量和生存时间具有一定意义。     

B超在小儿肠套叠诊断和临床辅助治疗中的应用价值分析

目的 探讨分析B超在小儿肠套叠诊断和临床辅助治疗中的应用价值分析.方法 将2009年4月1日至2013年4月1日我院收治的160例小儿肠套叠患儿按照抛硬币的方式随机分为两组,观察组和对照组,每组患儿80例.观察组采取B超对患儿进行小儿肠套叠诊断及临床辅助治疗,对照组采取腹部平片对患儿进行小儿肠套叠诊断及临床辅助治疗.比较两组患者的检出率和复位成功率.结果 通过两组比较,观察组的检出率(97.50％)显著高于对照组的检出率(57.50％),观察组的复位成功率(95.00％)显著高于对照组的复位成功率(62.50％),差异具有统计学意义(P＜0.05).结论 B超具有安全、精确等特点,在小儿肠套叠诊断及临床辅助治疗中具有很大的应用价值,深受临床的支持与关注,值得在临床上推广应用.     

The prognostic value of inflammation markers in postoperative gliomas with or without adjuvant treatments

Recent studies have shown that some inflammatory markers are associated with the prognosis of solid tumors. This study aims to evaluate the prognosis of glioma patients with or without adjuvant treatment using the systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR).All patients who were diagnosed with gliomas at the first and second affiliated hospital of Guangxi Medical University between 2011 and 2020 were included in this study. The optimal cutoff value of SII, NLR, and PLR was determined by X-tile software program. We stratified patients into several groups and evaluated the progression-free survival (PFS) and overall survival (OS) of SII, NLR, and PLR during the period of pre-surgical, con-chemoradiotherapy, and post-treatments. Multivariate Cox regression analyses were performed to detect the relationships between OS, PFS, and prognostic variables.A total of 67 gliomas patients were enrolled in the study. The cutoff values of SII, NLR, and PLR were 781.5 × 10⁹/L, 2.9 × 10⁹/L, and 123.2 × 10⁹/L, respectively. Patients who are pre-SII < 781.5 × 10⁹/L had better PFS (P = .027), but no difference in OS. In addition, patients who had low pre-NLR (<2.9 × 10⁹/L) meant better OS and PFS. PLR after adjuvant treatments (post-PLR) was significantly higher than pre-PLR (P = .035). Multivariate analyses revealed that pre-SII, pre-NLR were independent prognostic factors for OS (pre-SII: HR 1.002, 95% CI: 1.000–1.005, P = .030 and pre-PLR: HR 0.983, 95% CI: 0.973–0.994, P = .001), while pre-PLR was an independent factor for PFS (HR 0.989, 95% CI: 0.979–1.000, P = .041).High pre-SII or high pre-NLR could be prognostic markers to identify glioma patients who had a poor prognosis.     

Pharmacotherapy of head and neck cancer

Introduction: There are over 55,000 new cases of head and neck cancer diagnosed annually in the United States. Historically surgical resection was the standard of care, but due to vital structures in the head and neck region this led to severe morbidity. The integration of pharmacotherapy has rapidly expanded over the years into a multimodality treatment paradigm for locally advanced head and neck cancer, allowing organ-sparing treatment approaches. Here we discuss the various approaches and settings in which chemotherapy can be incorporated into the management of head and neck squamous cell carcinoma (HNSCC).

Areas covered: Chemotherapy in HNSCC can be administered in several different treatment circumstances: in the metastatic setting for palliation of symptoms and prolongation of survival, before definitive local treatment (induction), as part of definitive treatment simultaneously with radiation (concurrent) or after definitive local therapy (adjuvant).

Expert opinion: The incorporation of chemotherapy into the management of patients with head and neck cancer has allowed organ preservation approaches and improved survival. Because of the toxicities of chemotherapy, it is imperative that chemotherapy is only administered to the appropriate patient population who are more likely to benefit. Cisplatin 100 mg/m² given in combination with radiation in the non-metastatic setting is the most widely tested regimen and remains the reference regimen. Cetuximab is also an alternative, but there is no data to support the use of cetuximab in a laryngeal preservation approach or in the postoperative setting.