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.

Dosimetric Comparative Analysis of Volumetric Modulated Arc Therapy and Intensity-Modulated Radiation Therapy in Cervical Cancer

Objective:To carry out dosimetric comparison between volumetric modulated arc therapy(VMAT)and intensity-modulated radiation therapy(IMRT)in cervical cancer.Methods:50 postoperative cervical cancer patients were included in this study.The patients were admitted for treatment from January 2021 to January 2022.VMAT and IMRT plans were designed for each patient to analyze the dose distribution in the target area of the two treatment techniques.Results:Comparing the monitor unit for single treatment(638.21±116.21 MU)and time of single treatment(143.21±23.14 s)in the observation group and the monitor unit for single treatment(932.14±74.11 MU)and time of single treatment(223.14±17.26 s)in the control group,there was significant difference(P<0.05);there was also significant difference(P<0.05)between the normal tissue(bladder and rectum)of the observation group and that(bladder and rectum)of the control group.Conclusion:VMAT is more effective in cervical cancer,and it has a certain protective effect on normal tissues in patients and can reduce the radiation dose.

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.

Effect of external beam radiotherapy on patency of uncovered metallic stents in patients with inoperable bile duct cancer

BACKGROUND： Although biliary decompression with metallic stenting is the preferred treatment for inoperable bile duct cancer（BDC）, maintenance of patency is still unsatisfactory.We tried to assess the effectiveness and safety of external beam radiotherapy（EBRT） for prolonging stent patency in patients having uncovered metallic stents.METHOD： We retrospectively reviewed 50 patients who received endoscopic stenting, of whom 18 received EBRT（RT group） and 32 did not（non-RT group）.RESULTS： No difference was found in baseline characteristics between the two groups. Although stent patency was longer in the RT group than that in the non-RT group（140.7±51.3 vs136.4±34.9 days, P=0.94）, the difference was not statistically significant. There were a lower rate of stent occlusion（27.8% vs50.0% of patients, P=0.12） and a longer overall survival（420.1 ±73.2 vs 269.1±41.7 days, P=0.11） in the RT group than in the non-RT group, and the difference again was not statistically significant. The development of adverse reactions did not differ（55.6% vs 53.1% of patients, P=0.91）. There was no serious adverse reaction in both groups（P=0.99）.CONCLUSIONS： EBRT did not significantly improve stent patency in patients with inoperable BDC having uncovered metallic stents. However, EBRT was safe. Future trials withrefined protocols for better efficacy are expected.

Enhancement of radiosensitization by metal-based nanoparticles in cancer radiation therapy

Radiation therapy performs an important function in cancer treatment. However, resistance of tumor cells to radiation therapy still remains a serious concern, so the study of radiosensitizers has emerged as a persistent hotspot in radiation oncology. Along with the rapid advancement of nanotechnology in recent years, the potential value of nanoparticles as novel radiosensitizers has been discovered. This review summarizes the latest experimental findings both in vitro and in vivo and attempts to highlight the underlying mechanisms of response in nanoparticle radiosensitization.

Effects of postmastectomy radiotherapy on prognosis in different tumor stages of breast cancer patients with positive axillary lymph nodes

Objective: To explore the effects of postmastectomy radiotherapy(PMRT) on the locoregional failure-free survival(LRFFS) and overall survival(OS) of breast cancer patients under different tumor stages and with one to three positive axillary lymph nodes(ALNs). Methods: We conducted a retrospective review of 527 patients with one to three positive lymph nodes who underwent modified radical or partial mastectomy and axillary dissection from January 2000 to December 2002. The patients were divided into the T1-T2 N1 and T3-T4 N1 groups. The effects of PMRT on the LRFFS and OS of these two patient groups were analyzed using SPSS 19.0, Pearson's χ2-test, Kaplan-Meier method, and Cox proportional hazard model. Results: For T1-T2 N1 patients, no statistical significance was observed in the effects of PMRT on LRFFS [hazard ratio(HR)=0.726; 95% confidence interval(CI): 0.233-2.265; P=0.582] and OS(HR=0.914; 95% CI: 0.478-1.745; P=0.784) of the general patients. Extracapsular extension(ECE) and high histological grade were the risk factors for LRFFS and OS with statistical significance in multivariate analysis. Stratification analysis showed that PMRT statistically improved the clinical outcomes in high-risk patients [ECE(+), LRFFS: P=0.026, OS: P=0.007; histological grade III, LRFFS: P<0.001, OS: P=0.007] but not in low-risk patients [ECE(–), LRFFS: P=0.987, OS: P=0.502; histological grade I-II, LRFFS: P=0.816, OS: P=0.296]. For T3-T4 N1 patients, PMRT effectively improved the local control(HR=0.089; 95% CI: 0.210-0.378; P=0.001) of the general patients, whereas no statistical effect was observed on OS(HR=1.251; 95% CI: 0.597-2.622; P=0.552). Absence of estrogen receptors and progesterone receptors(ER/PR)(–) was an independent risk factor. Further stratification analysis indicated a statistical difference in LRFFS and OS between the high-risk patients with ER/PR(–) receiving PMRT and not receiving PMRT [ER/PR(–), LRFFS: P=0.046, OS: P=0.039]. However, PMRT had a beneficial effect on the reduction of locoregional recurrence(LRR) but not in total mortality [ER/PR(+), LRFFS: P<0.001, OS: P= 0.695] in T3-T4 N1 patients with ER/PR(+) who received endocrine therapy. Conclusion: PMRT could reduce ECE(+), histological grade III-related LRR, and total mortality of T1-T2 N1 patients. T3-T4 N1 patients with ER/PR(–) could benefit from PMRT by improving LRFFS and OS. However, PMRT could only reduce LRR but failed to improve OS for T3-T4 N1 patients with ER/PR(+) who received endocrine therapy.

Role of taxanes in pancreatic cancer

Pancreatic cancer is one of the most deadly cancers and is characterized by a poor prognosis. Single agent gemcitabine, despite its limited activity and modest impact on disease outcome, is considered as the standard therapy in pancreatic cancer. Most of the combination regimens used in the treatment of this disease, also including the targeted agents, did not improve the outcome of patients. Also, taxanes have been tested as single agent and in combination chemotherapy, both in first line and as salvage chemotherapy, as another possible option for treating pancreatic cancer. The inclusion of taxanes in combination with gemcitabine as upfront therapy obtained promising results. Accordingly, taxanes, and above all, new generation taxanes, appear to be suitable candidates for further testing to assess their role against pancreatic cancer in various clinical settings.

Experience with intraoperative radiotherapy for breast cancer: the Geneva University Hospital's experience

Background Breast conserving surgery along with adjuvant radiotherapy is effective in terms of local control and survival for early- stage breast cancer （1）. External beam radiotherapy （EBRT） following breast conserving surgery has been shown to improve survival by preventing local recurrence, in the Early Breast Cancer Trialists＇ Collaborative Group meta-analysis （2）. Standard radiotherapy typically requires numerous fractions over a 3-5 week period and is performed weeks or months after surgery or chemotherapy.

The Impact of Risk-Based Cancer Care Planning on the Complications and Self-Care Ability of Cervical Cancer Patients Undergoing Radiotherapy

Objective:To explore the impact of the application and implementation of risk-based cancer care planning in patients with cervical cancer radiotherapy on the complications and self-care ability of patients.Method:This study recruited selected patients who came for cervical cancer radiotherapy in a tertiary hospital in Xianyang City,Shaanxi Province from November 2020 to November 2021.One hundred patients were recruited.Nursing management was carried out,and cancer care planning under the concept of conventional care and risk were applied.The effects of different nursing methods on patients were compared and analyzed.Results:The patients in the experimental group had higher scores of self-care ability and lower complication rate.All data were significantly different from those of the control group(P<0.05),and the nursing effect on the experimental group was better.Conclusion:The application and implementation of the risk-based cancer care planning in patients who received cervical cancer radiotherapy has significant clinical effects,which is beneficial to reduce the incidence of patients’adverse reactions and promote patient recovery.

RADIOTHERAPEUTIC TOLERANCE OF THE RECONS-TRUCTIVE FLAPS FOLLOWING RADICAL EXCISION OF ORO-MAXILLOFACIAL CANCERS

Objectire To evaluate the radiation tolerance of the reconstructive flaPs used following radicalexcision of oro - maxillofacial tumors. methods The survival and radiation response of 88 flaps (preoperative 14and postoperative 74) in 82 patients were reviewed. Results The survival rate of 14 flaps done on preradiatedareas was 85.7% (12/14), markedly inferior to that of the flaps receiving postoperative radiation (98.6%, 73/74). Therate of radiation response of the flaps (35.1%) was signofcantly lower than that of the normal oral mucosasurrounding the flap (83.8%, P<0.01). Conclusion The good radiation tolerability of the transplants followingtumors excision pointed to the salety of its postoperative radiotherapy.

Effect of Compound Zhuye Shigao Granule(复方竹叶石膏颗粒)on Acute Radiation-Induced Esophagitis in Cancer Patients:A Randomized Controlled Trial

Objective： To observe the efficacy and safety of the Chinese medicine（CM） Compound Zhuye Shigao Granule（复方竹叶石膏颗粒, CZSG） on acute radiation-induced esophagitis（ARIE） in cancer patients. Methods： In a blinded, randomized, Kangfuxin Solution（康复新液, KFX）-controlled, single-centre clinical trial, 120 patients with lung, esophagus or mediastinal cancer were prospectively enrolled and assigned to the treatment group（60 cases） and control group（60 cases） by the random number table method. All patients received concurrent or sequential radiotherapy（2 Gy per day, 5 times per week, for 4 weeks） and were treated for 4 weeks since the radiation therapy. Patients in the treatment group were given 12 mg CZSG orally, thrice daily, while patients in the control group were given 10 m L KFX orally, thrice daily. The major indicators were observed, including the incidence and grade of esophagitis, time of occurrence and duration. Minor indicators were changes of CM symptoms, weight and Karnofsky Performance Status（KPS） Scale during 4 weeks from the beginning, recorded once a week. Blood routine examination and hepatorenal function were detected at the 2nd and 4th weeks. Results： The incidence and grade of ARIE were significantly decreased in the treatment group compared with the control group（P〈0.05）. CZSG appeared to significantly delay the time of ARIE occurrence and reduce the duration compared with KFX（P〈0.05）. The scores of CM symptoms, KPS and weight were improved significantly in the treatment group compared with the control group（P〈0.05）. There were no blood routine and hepatorenal function abnormal or obvious side-effects in both groups. Hemoglobin was improved and neutrophil and interleukin 6 were decreased in both groups after 4-week treatment compared with before treatment（P〈0.05）, and there was no significant difference between the two groups（P〉0.05）. Conclusions： CZSG can decrease the incidence and grade of ARIE, delay the time of occurrence, reduce duration and alleviate the damage of ARIE. It is safe and effective in the prevention and cure of ARIE.

Nanoparticles for targeted cancer radiotherapy

Radiotherapy,where ionizing radiation is locally delivered either through an external beam or by surgically implanting radionuclide-based seeds in the tumor,is one of the gold standard treatments for cancer.Due to the non-selective nature of radiation,healthy tissue surrounding the cancerous region is usually affected by the treatment.Hence,new strategies,including targeted alpha therapy,are being studied to improve the selectivity of the treatment and minimize side effects.Several challenges,however,limit the current development of targeted radiotherapy,such as the functionalization of the therapeutic agent with targeting vectors and controlling the release of recoiling daughters.Nanoparticles offer unique opportunities as drug delivery vehicles,since they are biocompatible,enhance the cellular uptake of drugs,and are easily functionalized with targeting molecules.In this review,we examine how nanoparticles can be used for targeted radiotherapy,either as sensitizers of external beams or as delivery vehicles for therapeutic radionuclides.We describe the clinical relevance of different types of nanoparticles,followed by an analysis of how these nanoconstructs can solve some of the main limitations of conventional radiotherapy.Finally,we critically discuss the current situation of nanoparticle-based radiotherapy in clinical settings and challenges that need to be overcome in the future for further development of the field.

Selectively enhancing radiosensitivity of cancer cells via in situ enzyme-instructed peptide self-assembly

The radiotherapy modulators used in clinic have disadvantages of high toxicity and low selectivity.For the first time,we used the in situ enzyme-instructed self-assembly(EISA)of a peptide derivative(Nap-GDFDFpYSV)to selectively enhance the sensitivity of cancer cells with high alkaline phosphatase(ALP)expression to ionizing radiation(IR).Compared with the in vitro pre-assembled control formed by the same molecule,assemblies formed by in situ EISA in cells greatly sensitized the ALPhigh-expressing cancer cells to y-rays,with a remarkable sensitizer enhancement ratio.Our results indicated that the enhancement was a result of fixing DNA damage,arresting cell cycles and inducing cell apoptosis.Interestingly,in vitro pre-formed assemblies mainly localized in the lysosomes after incubating with cells,while the assemblies formed via in situ EISA scattered in the cell cytosol.The accumulation of these molecules in cells could not be inhibited by endocytosis inhibitors.We believed that this molecule entered cancer cells by diffusion and then in situ self-assembled to form nanofibers under the catalysis of endogenous ALP.This study provides a successful example to utilize intracellular in situ EISA of small molecules to develop selective tumor radiosensitizers.