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  • ORIGINAL ARTICLE
    Haomeng Zhang, Yunkai Xie, Shuning Chen, Chunjie Piao, Chu Zhang, Weimin Kong
    Malignancy Spectrum, 2024, 1(3): 175-188. https://doi.org/10.1002/msp2.28

    Background: Cervical cancer is a highly aggressive cancer that seriously affects the physical and mental health and quality of life of women, especially for women in developing countries. Therefore, cervical cancer has always been the focus of research, and in recent years, various studies on cervical cancer have emerged one after another.

    Methods: Our study aimed to illustrate the development trends in cervical cancer research in China from 2013 to 2022 and compare the findings with studies in other parts of the world during the same period by using bibliometric analysis and the Science Citation Index Expanded. Literature data were analyzed and visualized by using CiteSpace and VOSviewer.

    Results: The results show that the number of articles on cervical cancer has increased in recent years, among which articles on the pathogenesis and epidemiological characteristics of cervical cancer account for the majority. The research in China has developed rapidly in recent years, but there is still a certain gap compared with other developed countries.

    Conclusion: Bibliometric and visualization analyses offer a unique and objective perspective in the field of cervical cancer and may assist scholars in identifying new research directions.

  • ORIGINAL ARTICLE
    Yubing Shen, Ruiying Fu, Xiaofeng Wang, Xinyu Zhang, Ying Zhou, Yiheng Zhou, Jue Liu, Dan Mei, Bingfeng Han, Li Li, Shaoming Wang, Ru Chen, Kexin Sun, Hong Lin, Huijuan Mu, Ke Sun, Hongmei Zeng, Wenqiang Wei
    Malignancy Spectrum, 2024, 1(3): 205-216. https://doi.org/10.1002/msp2.43

    Background: Population-based cancer survival is a key metric in evaluating the overall effectiveness of health services and cancer control activities. Advancement in information technology enables accurate vital status tracking through multi-source data linkage. However, its reliability for survival estimates in China is unclear.

    Methods: We analyzed data from Dalian Cancer Registry to evaluate the reliability of multi-source data linkage for population-based cancer survival estimates in China. Newly diagnosed cancer patients in 2015 were included and followed until June 2021. We conducted single-source data linkage by linking patients to Dalian Vital Statistics System, and multi-source data linkage by further linking to Dalian Household Registration System and the hospital medical records. Patient vital status was subsequently determined through active follow-up via telephone calls, referred to as comprehensive follow-up, which served as the gold standard. Using the cohort method, we calculated 5-year observed survival and age-standardized relative survival for 20 cancer types and all cancers combined.

    Results: Compared to comprehensive follow-up, single-source data link-age overestimated 5-year observed survival by 3.2% for all cancers combined, ranging from 0.1% to 8.6% across 20 cancer types. Multi-source data linkage provided a relatively complete patient vital status, with an observed survival estimate of only 0.3% higher for all cancers, ranging from 0% to 1.5% across 20 cancer types.

    Conclusion: Multi-source data linkage contributes to reliable population-based cancer survival estimates in China. Linkage of multiple databases might be of great value in improving the efficiency of follow-up and the quality of survival data for cancer patients in developing countries.

  • ORIGINAL ARTICLE
    Wei Li, Zhaoxin Chen, Mingjun Lu, Zhendong Lu, Siyun Fu, Yuhua Wu, Hong Tao, Liang Shi, Teng Ma, Jinghui Wang
    Malignancy Spectrum, 2024, 1(3): 162-174. https://doi.org/10.1002/msp2.41

    Background: Immunotherapy combined with chemotherapy has been approved as first-line therapy for small cell lung cancer (SCLC) due to the survival benefit in randomized controlled trials. However, predicting its efficacy remains a challenge in the absence of currently available biomarkers.

    Methods: A total of 140 individuals with SCLC who received immunotherapy were evaluated retrospectively. These patients were split into two distinct cohorts, the discovery cohort (80% of the total, n = 112) and the validation cohort (20% of the total, n = 28). The objective response rate (ORR), disease control rate (DCR), and responder (progression-free survival [PFS] > 6 months) were all predicted using neural networks.

    Results: We developed predictive models for three clinical outcomes. ORR scored 0.8964 area under the receiver operating characteristic curve (AUC) in the discovery cohort and 0.8421 AUC in the validation cohort. DCR model had AUC of 0.8618 in the discovery cohort and AUC of 0.7396 in the validation cohort. The responder model had AUC of 0.8116 in the discovery cohort and AUC of 0.7041 in the validation cohort. The models were then compressed into a doctor-friendly tool.

    Conclusion: These neural network-based models, which are based on routine clinical characteristics, accurately predict the efficacy of immunotherapy in patients with SCLC, particularly in terms of ORR.

  • ORIGINAL ARTICLE
    Zhenjie Dai, Jing Chen, Yong Wang
    Malignancy Spectrum, 2024, 1(3): 197-204. https://doi.org/10.1002/msp2.40

    Background: The effects of programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) immune checkpoint inhibitors (ICIs) in patients with squamous and nonsquamous non-small cell lung cancer (NSCLC) remain controversial. We conducted a meta-analysis to summarize the existing evidence on this topic.

    Methods: We searched PubMed, Medline, and Embase for studies published before December 1, 2022, comparing PD-1/PD-L1 ICIs with docetaxel in squamous and nonsquamous NSCLC patients in any language. The different hazard ratio (HR) values for overall survival (OS) and progression-free survival (PFS) were calculated in this study.

    Results: A total of seven studies were identified. In a summary analysis of all studies, the HR values of OS in patients with nonsquamous and squamous NSCLC were 0.73, 95% confidence interval (CI): 0.67–0.79 and 0.70, 95% CI: 0.62–0.79, respectively. In patients with PD-L1 expression levels of 1% or higher, the HR values of OS in nonsquamous and squamous NSCLC patients were 0.60, 95% CI: 0.49–0.74 and 0.72, 95% CI: 0.54–0.96, respectively. The HR values of OS in nonsquamous and squamous NSCLC patients with PD-L1 expression levels of 5% or higher were 0.46, 95% CI: 0.35–0.59 and 0.55, 95% CI: 0.39–0.79, respectively. In nonsquamous and squamous NSCLC patients with PD-L1 expression levels of 10% or higher, the HR values of OS were 0.42, 95% CI: 0.32–0.54, and 0.53, 95% CI: 0.36–0.78, respectively.

    Conclusion: The meta-analysis demonstrated possible evidence that there was different efficacy of PD-1/PD-L1 ICIs on OS in squamous and nonsquamous NSCLC patients with different PD-L1 expression levels. Subgroup analysis showed that there was a greater OS benefit in patients with nonsquamous NSCLC.

  • REVIEW
    Jiaxin Zhong, Xiaorong Lin, Hai Hu
    Malignancy Spectrum, 2024, 1(3): 147-161. https://doi.org/10.1002/msp2.29

    Antigen presentation, as the initial step in inducing the activation of T lymphocytes, plays a crucial role in antitumor response. Studies concentrating on major histocompatibility complex class II (MHC II) molecules and the activated CD4+ helper T (Th) cells have gained popularity in light of the past limited efficacy of MHC I-activated CD8+ T cells alone. In general, MHC II is canonically expressed by professional antigen-presenting cells (pAPCs), yet attempts to increase antigen presentation by dendritic cell (DC) activation have mostly been unsuccessful. In recent years, a number of studies have found that a variety of cells, including cancer cells, fibroblasts, vascular endothelial cells (VECs), and lymphoid stromal cells (LSCs), are considered amateur APCs (aAPCs) and can express MHC II molecules, which have piqued the interest of researchers. These groups vastly outnumber DCs or macrophages, and it has been confirmed that they also qualify as antigen-presenting complexes that are functionally related to conventional pAPCs. Herein, we will review current research regarding the antigen presentation process of MHC II, its advances in APC surfaces, especially for aAPCs, the special mechanisms of regulation of MHC II on aAPCs, and combination therapy targeting MHC II as a possible treatment strategy in cancer.

  • ORIGINAL ARTICLE
    Behzat Can, Ezgi Roza Gül, Hüseyin Salih Semiz, Kemal Hansu, Volkan Karataşlı, Sevil Sayhan, Muzaffer Sancı
    Malignancy Spectrum, 2024, 1(3): 189-196. https://doi.org/10.1002/msp2.42

    Background: This study aimed to explore the impact of patient-specific factors on the effectiveness of platinum-based chemotherapy in ovarian cancer patients. Specifically, we investigated the relationship between estrogen receptor (ER) and progesterone receptor (PR) expression levels and platinum sensitivity, and how this influenced treatment outcomes and prognosis. We conducted a survival analysis on patients who underwent surgical treatment for serous ovarian cancer and received platinum-based adjuvant therapies.

    Methods: This study was a retrospective observational analysis of 171 patients with high-grade serous ovarian cancer. We extracted and analyzed the patients’ clinical data, focusing on platinum sensitivity concerning hormone receptor expression. We also assessed survival outcomes based on receptor expression and platinum resistance.

    Results: Our findings revealed that 78.4% (n = 134) of the patients were platinum-sensitive, while 21.6% (n = 37) were platinum-resistant. The expression of hormone receptors showed significant associations with platinum sensitivity, particularly among ER-positive patients (p<0.05). Age, disease stage, preoperative carbohydrate antigen 125 (CA125) levels, and residual tumor size were identified as notable factors influencing both progression-free survival (PFS) and overall survival (OS). In terms of PFS, 88.5% of patients remained free from disease progression after one year, but this percentage dropped to 21% after five years. The average duration of PFS was 35.3 months. As for OS, 93.5% of patients were still alive after one year, but this percentage decreased to 50.5% after five years. The average survival duration was 64 months. Furthermore, platinum resistance was found to be a significant risk factor for disease progression, with a more than fivefold increase in risk (p < 0.001).

    Conclusion: Our study identified disease stage progression, ER negativity, and platinum resistance as the primary factors influencing OS. We also found that ER and PR expression played a crucial role in determining the sensitivity to platinum-based chemotherapy in patients with serous ovarian cancer.

  • PERSPECTIVE
    Kai-Feng Pan, Wen-Qing Li, Wei-Cheng You
    Malignancy Spectrum, 2024, 1(3): 141-146. https://doi.org/10.1002/msp2.38

    Gastric cancer (GC) is a global public health burden, with nearly one million new cases diagnosed each year worldwide. To investigate the risk factors and the prevention strategies for GC, in the past 40 years, a series of epidemiological studies have been carried out in Linqu County, Shandong Province, a high-risk area of GC in China. Here, we briefly review the major efforts of 40-year practices against GC in Linqu County, particularly highlighting a case-control study to identify GC risk factors, a cohort study to determine the associations between the risk factors and the progression of gastric lesions, and an intervention trial to prevent GC development.

  • CASE REPORT
    Jing Wu, Yuehong Cui, Shan Yu
    Malignancy Spectrum, 2024, 1(3): 217-222. https://doi.org/10.1002/msp2.39

    Objective: This study aimed to report the treatment and outcomes of a patient with advanced gastric cancer (GC) using a combination of a targeted molecular therapy and chemotherapy.

    Patients and methods: A 40-year-old woman presented with abdominal metastatic nodules and peritoneal effusion. Biopsy and cytology identified signet ring cell carcinoma. Ten months after the onset of initial symptoms, gastroscopy confirmed signet ring cell carcinoma of the gastric body. Genetic testing revealed amplification of the fibroblast growth factor receptor (FGFR) gene. Consequently, the patient received FGFR inhibitor pemigatinib in addition to a chemotherapy regimen of albumin paclitaxel plus 5-fluorouracil.

    Results: During the treatment, the patient experienced recurrent liver function abnormalities and intestinal obstruction, which were managed with symptom-specific medications and supportive therapies. The combined treatment regimen resulted in a progression-free survival (PFS) period of ten months.

    Conclusion: The integration of FGFR inhibitor pemigatinib with standard chemotherapy showed promising results in prolonging PFS in a patient with advanced GC characterized by FGFR gene amplification, despite the occurrence of manageable side effects.

  • ORIGINAL ARTICLE
    Kenjiro Namikawa, Kok Yew Ngew, Zuzanna Lukowicz, Ryosuke Kano
    Malignancy Spectrum, 2024, 1(4): 312-322. https://doi.org/10.1002/msp2.51

    Objective: This study aimed to describe patients with melanoma initiating treatments with dabrafenib plus trametinib (Dab + Tram) or encorafenib plus binimetinib (Enco + Bini) in a real-world setting in Japan.

    Methods: Data were extracted from the Japanese Medical Data Vision (MDV) insurance claims database. Patients diagnosed with melanoma between 2012 and 2021 and prescribed with Dab + Tram or Enco + Bini were included in three cohorts: non-adjuvant Dab + Tram, adjuvant Dab + Tram, and Enco + Bini. Data were extracted on patient characteristics at treatment initiation. During follow-up, all changes in melanoma treatments were documented. Treatment adherence was determined as the proportion of prescription days covered (PDC) and treatment dose intensity as the relative dose intensity (RDI).

    Results: Sixty-seven patients were included in the non-adjuvant Dab + Tram cohort (55 first-line treatments), seven in the adjuvant Dab + Tram cohort (six first-line treatments), and 16 in the Enco + Bini cohort (four first-line treatments). The mean age was 61.3 ± 13.5 years and 56.1% were men. Twenty-seven patients with non-adjuvant Dab + Tram or Enco + Bini in first line (45.8%) switched to a second line. The median treatment duration was 11.8 months for Dab + Tram and 8.1 months for Enco + Bini. A PDC ≥ 80% was observed for 85.7% of patients with adjuvant Dab + Tram, 68.7% for non-adjuvant Dab + Tram, and 75.0% for Enco + Bini. Median RDI was 1.0 for adjuvant Dab + Tram, 0.9 for non-adjuvant Dab + Tram, and 0.6 for Enco + Bini.

    Conclusion: Dab + Tram is used consistently with clinical practice guide-lines in the adjuvant setting, but adherence in the non-adjuvant setting is suboptimal, as is the prescribed dose of Enco + Bini. Prescribers should ensure that these therapies are used in an optimal way to improve outcomes in melanoma.

  • CASE REPORT
    Alejandro Caballero, Mario Perez, Issis Rodriguez
    Malignancy Spectrum, 2024, 1(4): 339-345. https://doi.org/10.1002/msp2.49

    Objective: This study aimed to report the treatment and outcomes of a patient with primary malignant melanoma of the breast parenchyma using mastectomy as the main treatment.

    Patient and methods: A 67-year-old female presented with a palpable lump approximately 2 cm in diameter in the lower inner quadrant of the left breast, and underwent ultrasound guided cutting needle biopsy. Cytological examination identified a malignant melanoma of the breast, and she received treatment with a modified radical mastectomy. Further assessment was carried out using a positron emission tomography/computed tomography, which negated the presence of a primary lesion in either adjacent or distant sites.

    Results: After three years of follow-up with ultrasonography (USG) and mammography annually and a complete physical examination every six months in the clinic, the patient remained alive with no evidence of local or distant recurrence.

    Conclusion: The surgical management of this case is appropriate according to the available literature up to the present. We recommend BRAF mutation testing and melanocytic marker testing for all patients to ensure the correct focus when selecting biomarker-based immunotherapy.

  • ORIGINAL ARTICLE
    Hamsaveni Muthukumar, Wesley Mannirathil Jose, Nikhil Krishna Haridas, Anjali Sajikumar Nair, Keechilat Pavithran
    Malignancy Spectrum, 2024, 1(4): 332-338. https://doi.org/10.1002/msp2.54

    Objective: Cancer patients have a 4–7-fold increased risk of thrombotic complications due to cancer as well as chemotherapy-induced hypercoagulable state. This study compared the different risk assessment models (Khorana, PROTECHT, CONKO, and COMPASS-CAT scores) that help predict venous thromboembolism (VTE) in ambulatory cancer patients. Early identification of high-risk patients would benefit from thromboprophylaxis, thereby improving the mortality and morbidity due to thrombotic events.

    Methods: This is a single-center, prospective, cross-sectional study on ambulatory patients with solid malignancy. The study was conducted over six months, from March 2022 to August 2022. Data on VTE predictors were gathered from 230 ambulatory cancer patients undergoing chemotherapy.

    Results: Among the 230 patients receiving chemotherapy, 20 were diagnosed with VTE, with the majority of this population being either diagnosed with gynecological cancer or lung cancer, constituting 25% of VTE-diagnosed patients. The Khorana score, with a VTE accuracy of 83.04%, was found to be the highest, followed by the CONKO (80.00%), PROTECHT (69.57%), COMPASS-CAT Ⅱ (54.35%), and COMPASS-CAT Ⅰ (38.26%) scores. The cumulative incidence of VTE among high-risk patients showed that the PROTECHT score had the highest cumulative incidence (CI = 14.28), and the CONKO score had the lowest (CI = 9.40).

    Conclusion: The Khorana score was the most accurate, followed by the CONKO, PROTECHT, and COMPASS-CAT Ⅱ scores, while the COMPASS-CAT Ⅰ score was the least accurate. Hence, the Khorana scoring is essential for diagnosing VTE in patients with ambulatory cancer treated with chemotherapy.

  • ORIGINAL ARTICLE
    Xinyuan Zhang, Xiaohong Zhang, Xingu Chen, Shuping Liang, Yan Yu, Hui Li, Qunqing Chen, Li Li
    Malignancy Spectrum, 2025, 2(1): 1-12. https://doi.org/10.1002/msp2.70001

    Objective: This study aimed to evaluate the effects of graded motor imagery (GMI) on fear of movement, pain, and rehabilitation in patients with kinesiophobia after video-assisted thoracoscopic surgery (VATS) for lung cancer.

    Methods: Fifty-eight participants with kinesiophobia after VATS were randomly assigned into two groups: one receiving usual care (the control group) and the other receiving usual care plus GMI (the GMI group). The GMI was delivered in three stages: left/right limb identification, motor imagery, and mirror therapy delivered by two researchers every afternoon starting on the first postoperative day, once a day for about 40 min, at least twice. Level of fear of movement, pain-related patient-reported outcomes (PROs), rehabilitation exercise participation, and peak expiratory flow (PEF) were compared between the two groups.

    Results: Twenty-seven eligible participants were included in the GMI group and 29 in the control group. Compared to the reports on the first postoperative day, the participants who received GMI reported at discharge significant reductions in kinesiophobia, intensity of worst pain and least pain, and interference of pain with activities and emotions, and increases in rehabilitation exercise participation and PEF than those in the control group (p < 0.05). An unexpected finding was a reduced surgery-to-discharge interval in the patients who received GMI (almost a day earlier than those in the control group).

    Conclusion: GMI can reduce fear of movement, improve pain-related PROs, and increase rehabilitation exercise participation and PEF for lung cancer patients with kinesiophobia after VATS.

    The study was registered at the Chinese Clinical Trial Registry (ChiCTR2300072612).

  • ORIGINAL ARTICLE
    Zeeshan Afzal, Sara Hira, Xia Song, Na Wang
    Malignancy Spectrum, 2024, 1(4): 300-311. https://doi.org/10.1002/msp2.46

    Background: Platinum-based chemotherapy in addition to the non-platinum agent etoposide is the standard of care for extensive-stage small cell lung cancer (ES-SCLC). However, the front-line chemotherapy regimen is not known. Therefore, we aimed to perform this review comparing irinotecan/carboplatin (IC) and etoposide/carboplatin (EC) in patients of extended disease small cell lung cancer (ED-SCLC).

    Methods: We searched three databases, that is, PubMed, Embase, and Cochrane Library. The outcomes for complete response (CR), median overall survival (OS), and progression-free survival (PFS) were evaluated. In addition, adverse events such as leukopenia, thrombocytopenia, anemia, diarrhea, and infections were also assessed. RevMan 5.4.1 was used to perform the statistical analysis.

    Results: Three randomized controlled trials (RCTs) with 676 patients were included. There was a significant difference between IC and EC arms in terms of CR (risk ratio [RR] = 2.52; 95% confidence interval [CI]: 1.20–5.32; p = 0.02, I2 (i.e., the percentage of the total variance that is due to between-study heterogeneity) = 0%), leukopenia (RR = 0.47; 95% CI: 0.23–0.97; p = 0.04; I2 = 90%), amimia (RR = 0.55; 95% CI: 0.38–0.78; p = 0.0008; I2 = 0%), thrombocytopenia (RR = 0.51; 95% CI: 0.39–0.68; p = 0.00001; I2 = 0%), and diarrhea (RR = 4.88; 95% CI: 1.64–14.49; p = 0.004; I2 = 33%). There was no statistically significant difference between IC and EC arms in terms of median OS (hazard ratio [HR] = 1.16; 95% CI: 0.84–1.62; p = 0.37; I2 = 74%), PFS (HR = 1.04; 95% CI: 0.69–1.56; p = 0.85; I2 = 77%), nausea (RR = 1.70; 95% CI: 0.76–3.81; p = 0.19; I2 = 0%), infection (RR = 0.97; 95% CI: 0.64–1.48; p = 0.89; I2 = 0%), and treatment-related deaths (RR = 0.58; 95% CI: 0.24–1.42; p = 0.23; I2 = 0%).

    Conclusion: This meta-analysis provides valuable evidence supporting the superiority of IC regimens over EC regimens in terms of CR and toxicity profile for ED-SCLC.

  • REVIEW
    Dandan Wang, Yiwei Zhao, Yiyun Zeng, Lanlin Hu, Chuan Xu
    Malignancy Spectrum, 2024, 1(4): 225-242. https://doi.org/10.1002/msp2.50

    Immunotherapy, particularly immune checkpoint inhibitors (ICIs), has radically transformed the field of oncological therapy. However, immune‐related adverse events (irAEs) associated with the treatment might affect the life quality and even threaten the life of cancer patients. Immunotherapy-mediated colitis (IMC) is one of the most prevalent irAEs, especially in anti-cytotoxic T lymphocyte antigen 4 antibody (CTLA4) therapy. Current management of IMC includes administering immunosuppressants and discontinuing the treatment, which might affect the therapeutic efficacy. In this review, we briefly summarize the development of ICIs in cancer immunotherapy and the incidence, diagnosis, and management of IMC. Recent insights into the cellular and molecular pathways that underpin IMC, perspective research, and promising therapeutic strategies are highlighted. Further understanding of IMC and its implications will assist clinicians in optimizing treatment strategies to mitigate this side effect while maximizing the benefits of ICIs.

  • ORIGINAL ARTICLE
    Xuemin Li, Hao Wang, Yuliang Jiang, Zhe Ji, Haitao Sun, Jinghong Fan, Weiyan Li, Junjie Wang
    Malignancy Spectrum, 2024, 1(4): 323-331. https://doi.org/10.1002/msp2.55

    Objective: This study aimed to investigate the accuracy of needle insertion and dosimetric parameters in three-dimensional printing template (3D-PT)-assisted computed tomography (CT)-guided radioactive iodine-125 (125I) seed implantation (RISI) for the treatment of peripheral locally recurrent rectal cancer (pLRRC).

    Materials and methods: A total of 37 patients with pLRRC who underwent 3D-assisted CT-guided RISI treatment at Peking University Third Hospital between January 2016 and November 2019 were included in this study. All patients underwent preoperative assessment, CT simulation positioning, preoperative plan design, 3D template printing, 3D template reduction, needle and seed implantation, postoperative dosimetry evaluation, post-operative care, and regular follow-up. The preoperative and postoperative needle position, angle, and tip distance were compared. The dosimetric parameters, including D90 (the dose to 90% of the target volume), D100, V100 (the volume receives 100% of the prescribed dose), V150, V200, conformal index (CI), external index (EI), and homogeneity index (HI), were compared among preoperative plan, intraoperative plan, and postoperative plan. The perioperative complications were assessed.

    Results: The total number of needles was 595. The depths of needle insertion in preoperative and intraoperative plans were 109.87 ± 1.33mm and 108.46 ± 1.26 mm, respectively, with no significant difference (p > 0.05). The angles of needle insertion in preoperative and intraoperative plans were (93.55 ± 2.05)° and (92.04 ± 1.99)°, respectively, with no significant difference (p > 0.05). The average deviation of the needle insertion distance was 1.99 ± 0.08 mm. There were no differences in preoperative, intraoperative, and postoperative parameters, including D90, D100, V100, V150, V200, CI, EI, and HI. All patients were closely followed up during the perioperative period (from seven days before surgery to seven days after surgery). No patients experienced severe perioperative complications. A total of eight patients (21.6%) experienced grade 1–2 complications. Among all patients, six individuals (16.2%) experienced pain, one patient (2.7%) had a fever, and one patient (2.7%) suffered from a hemorrhage. All patients recovered after conservative treatment.

    Conclusion: The needle insertion in 3D-PT-assisted CT-guided RISI showed good accuracy for treating pLRRC.

  • REVIEW
    Susu Xiao, Xiaoxiao Wang, Bo Chen, Min Mu, Bo Han, Nianyong Chen, Gang Guo
    Malignancy Spectrum, 2024, 1(4): 243-262. https://doi.org/10.1002/msp2.52

    Radiotherapy (RT) plays a crucial role in tumor treatment and is an indispensable therapeutic approach. However, ionizing radiation often damages the normal tissues surrounding the tumor. Therefore, there is an urgent need for effective methods to improve the precision of RT. Nanotechnology has shown potential in enhancing the efficacy and safety of tumor RT. With the continuous development of multifunctional nanomaterials, various nanomaterials have been designed and investigated as radiation enhancers. Metallic nanomaterials are considered as promising radiosensitizers with potential for clinical translation. High atomic number (high-Z) metal nanoparticles (NPs), such as gold and bismuth, have garnered increasing attention for their ability to enhance the radiation effect, as they can potentially improve RT outcomes. New nanomedicine strategies may help to advance RT. This paper concisely explains the radiation enhancement mechanisms of high-Z metal NPs. It also enumerates several commonly studied high-Z metallic nanomaterials used in tumor RT and discusses their potential clinical applications.

  • REVIEW
    Ela Kesen Boztas, Sevki Mustafa Demiroz, Hacer Ilke Onen
    Malignancy Spectrum, 2024, 1(4): 263-274. https://doi.org/10.1002/msp2.53

    Lung cancer is the leading malignancy among males and ranks the second in females, with an estimated two million new diagnoses annually. It ranks the first in cancer-related deaths among men and the second, following breast cancer, among women. The most significant risk factor for lung cancer is smoking. There are two main types of lung cancer: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), with about 85% of cases falling into the NSCLC category. Even with a combination of treatments for NSCLC, such as surgical intervention, chemotherapy, radiation therapy, and immunotherapy, the 5-year survival rates for those diagnosed with advanced NSCLC have not reached satisfactory levels, with chemotherapy continuing to be the main therapeutic approach. In advanced NSCLC treatment, gemcitabine and platinum-based agents are applied as first-line therapy. However, acquired or pre-existing drug resistance can prevent chemotherapeutic agents from achieving the expected effect on patients and increasing the drug dose can lead to an increase in side effects. In recent years, for these reasons, there has been an increased interest in phytochemicals to enhance the cytotoxic effects of therapeutic agents on cancer cells while minimizing their toxic effects on healthy tissues. One of the most studied phytochemicals is curcumin. Despite its anticancer effects on NSCLC cells, its low stability and poor pharmacokinetics have led to unsatisfactory results in studies. Therefore, a variety of analogs have been synthesized. This review explores the impact of curcumin and its analogs on the pathways of cell death in NSCLC.

  • ORIGINAL ARTICLE
    Payal Sharma, Ishan Kumar, Ritu Ojha, Seema Khanna, Ashish Verma
    Malignancy Spectrum, 2024, 1(4): 290-299. https://doi.org/10.1002/msp2.45

    Background: Classification of breast cancer based on gene expression has emerged as the standard approach in its management, owing to the distinct prognoses and treatment responses observed among different subtypes. The aim of this study was to prospectively assess the imaging features of the molecular subtypes of breast cancer using multiparametric magnetic resonance imaging (mMRI) with the combined assessment of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), diffusion-weighted imaging (DWI), and MR spectroscopy (MRS).

    Methods: This was a prospective observational single-center cohort study, which included women with BI-RADS 4–5 lesions on mammography/ultrasound (US) who subsequently underwent 1.5 T MRI (encompassing DCE-MRI, DWI, and MRS). The histological subtypes of breast cancer were assessed. Estrogen receptor (ER), progesterone receptor (PR), Ki-67 status, and human epidermal growth receptor-2 (HER2) expression, assessed by immunohistochemistry (IHC), defined four molecular subtypes: luminal A, luminal B, HER2-enriched (Her2en), and triple-negative breast carcinoma (TNBC). Statistical associations between the four molecular subtypes and MRI features were investigated.

    Results: Fifty patients were included in the study. Circumscribed margins were significantly correlated with triple-negative tumors compared to others (78% versus 6%, p < 0.001). Spiculated margins were observed in nontriple negative tumors. Rim enhancement was significantly correlated to triple-negative tumors compared to all other subtypes (71.4% versus 25%, p = 0.035). Mean apparent diffusion coefficient (ADC) values were significantly lower for luminal subtypes compared to non-luminal subtypes (p < 0.001). The total choline (tCho) signal-to-noise ratio (SNR) was higher in triple-negative tumors. A combined algorithm using DCE-MRI, DWI, and MRS can predict TNBC and Her2en with specificity of 86.6% and 100%, respectively, and sensitivity of 100% and 85.37%, respectively.

    Conclusion: The combination of mMRI with DCE-MRI, DWI, and MRS can accurately differentiate the molecular subtypes of breast carcinoma.

  • EDITORIAL
    Zi Wang, Wenfeng Tu, Yi Yang
    Malignancy Spectrum, 2024, 1(4): 223-224. https://doi.org/10.1002/msp2.31
  • ORIGINAL ARTICLE
    Chuanshi He, Mingzhe Xie, Zhimi Zhang, Bangrong Cao, Huaichao Luo, Guiquan Zhu, Shun Lu, Ling Li
    Malignancy Spectrum, 2024, 1(4): 275-289. https://doi.org/10.1002/msp2.44

    Background: Cancer-associated fibroblasts (CAFs), the main matrix components in the tumor microenvironment (TME), play a crucial role in tumor progression. Extracellular vesicles (EVs) as main mediators in intercellular communication can be regulated by hypoxia or radiation.

    Methods: CAFs were extracted from head and neck squamous cell carcinoma (HNSCC) tissues and CAF-derived EVs were collected by ultracentrifugation. Bioinformatics analysis determined the role of poly (U)-specific endonuclease (ENDOU) on HNSCC progression and confirmed that ENDOU inhibited HNSCC progression by overexpressing ENDOU in HNSCC. Dual-luciferase activity report assay confirmed that miR-23b-5p was involved in the regulation of ENDOU expression. The migration and invasion of HNSCC cells were verified by transwell assay. Furthermore, tumor-bearing mouse models were used to demonstrate the potential of EVs loaded with miR-23b-5p in HNSCC to promote tumor progression.

    Results: Our results showed that ENDOU was downregulated in HNSCC and inhibited HNSCC migration and invasion. Hypoxia and radiotherapy reversed CAF-derived EVs to promote migration and invasion of HNSCC. Mechanically, hypoxia and radiation downregulated miR-23b-5p in CAF-derived EVs and then restored ENDOU expression in HNSCC. Finally, CAF-derived EVs carrying miR-23b-5p promoted the progression of HNSCC cells in vivo by regulating ENDOU expression.

    Conclusion: This study demonstrated that hypoxia combined with radiation reverses the promoting effect of CAFs on HNSCC migration and invasion by reducing the delivery of miR-23b-5p by CAF-derived EVs to decrease the inhibitory effect of ENDOU expression in HNSCC. The results provide a new perspective for better understanding the role of stromal components in TME in tumor regulation. Furthermore, the results provide a strong basis for the possibility of ENDOU as a biomarker for HNSCC.

  • ORIGINAL ARTICLE
    Feifei Liu, Man Hu, Rui Zhang, Zhigang Li, Hongyun Lian
    Malignancy Spectrum, 2025, 2(1): 53-58. https://doi.org/10.1002/msp2.70003

    Background: Juvenile xanthogranuloma (JXG) is a rare disorder that belongs to the broad group of non-Langerhans cell histiocytosis. It is characterized by one or more nodules with predilection sites on the head, neck, and trunk, and lesions that may be several millimeters in diameter. These are reddish or yellowish benign papules or nodules that usually resolve spontaneously. The involvement of organs other than the skin is termed systemic juvenile xanthogranuloma (SJXG). The eye is the most frequent extracutaneous location of the JXG.

    Case presentation: We report a case of SJXG in a male child, with onset in the second month of life. He presented with several nodules, approximately 5 mm in diameter and tan-orange in color, located on the head, face, and trunk. The nodules enlarged to 10 mm in diameter, and new lesions were found in the right eye, which resulted in spontaneous hyphema and secondary glaucoma without treatment. The pathological findings suggested that the nodule was of histiocytic origin, and immunohistochemical analysis resulted in the diagnosis of JXG. Chemotherapy based on the Langerhans cell histiocytosis (LCH) regimen resulted in a good prognosis.

    Conclusion: SJXG has low morbidity, but is unpredictable, and rare and self-limited. Treatment is required for patients with extracutaneous involvement, who may have increased morbidity. The LCH-Ⅲ protocol of the International Histiocyte Society is the most commonly used and effective chemotherapy regimen.

  • ORIGINAL ARTICLE
    Mohammad Reza Foroughi-Gilvaee, Alireza Jahandideh, Mohammad Faranoush, Reza Nekouian
    Malignancy Spectrum, 2025, 2(1): 13-25. https://doi.org/10.1002/msp2.57

    Background: Breast cancer is a major cause of mortality globally. Oncolytic virotherapy is a promising treatment modality that directly destroys cancer cells and induces an immune response against them. Among natural oncolytic viruses, Newcastle disease virus (NDV) has shown selective tumor cell infection.

    Materials and methods: In this study, we investigated the efficacy of variable doses of NDV and cyclophosphamide on 4T1 cancer cell line and BALB/c mouse tumors for the first time.

    Results: Compared with the control group, the combination treatment group with NDV and cyclophosphamide showed a significant increase in the expression levels of P21, P27, and P53 genes by 38%, 46%, and 81%, respectively (p < 0.05). In contrast, the expression levels of CD34, integrin α5, vascular endothelial growth factor (VEGF), and vascular endothelial growth factor receptor (VEGFR) genes significantly decreased by 47%, 45%, 42%, and 23%, respectively (p < 0.05). The reactive oxygen species (ROS) generation assay evaluated with 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) staining showed a significant increase in ROS levels within 4T1 cells treated with NDV compared with the untreated group after 24 h (p < 0.01). Furthermore, Annexin V/propidium iodide (PI) double staining analysis showed that the proportion of apoptotic cells in the NDV-treated group decreased by 0.61% and 1.63% after 6 h and 12 h, respectively (p < 0.05). After 12 days, tumor volume in the NDV-treated groups decreased by 72%−87% compared with a 48% increase in the control group, reflecting a net reduction in tumor volume relative to the control group (p < 0.001).

    Conclusion: These findings demonstrate that NDV in combination with chemotherapy drugs may be a promising therapeutic option for cancer patients. However, several other factors need to be considered. These results indicate that NDV may have potential effects on cancer treatment.

  • ORIGINAL ARTICLE
    Emma R. Allanson, Vera Velanova, Boniface Damutalau, Harriet Obed, Geetha Warrier, Ian H. Frazer, Margaret McAdam
    Malignancy Spectrum, 2025, 2(1): 46-52. https://doi.org/10.1002/msp2.70004

    Aims: Vanuatu is a lower- and middle-income country in the Pacific with a cervical cancer incidence of 100 per 100,000 women. An opportunistic screening program has existed since 2008, with continuous data collection related to this since 2015.

    Methods: We analysed all cervical cancer screening data for Vanuatu over 6 years, and conducted a descriptive analysis of number of women screened, the results of screening, the treatment rates of human papillomavirus (HPV) positivity or cytological abnormalities detected through screening, and the incidence of cervical cancer. The challenges encountered during the implementation of the screening program are also described.

    Results: Data were available from 01/01/2015 to 31/12/2020. Based on census data, 70,081 women were eligible for screening, and 15,696 (22.4%) women underwent screening at least once. Screening coverage included 13.2% of individuals under 30 years, 33.2% of individuals in the 30−50 age group, and 15.8% of people over 50 years. A total of 8910 HPV tests were conducted, of which 876 (9.8%) were positive. Among the HPV-positive cases, 316 received large loop excision of the transformation zone (LLETZ) treatment, 156 (49.4%) of which were high grade and 2 (0.6%) of which were cancer. A total of 13,396 Pap smear tests were conducted, with 315 (2.4%) showing high-grade results and 226 (1.7%) indicating possible high-grade results. Overall, 119 cancers were diagnosed from 15,696 women screened (0.8%), including 6/3297 (0.2%) of < 30 years, 75/10,089 (0.7%) of 30−50 years, 38/2310 (1.6%) of > 50 years.

    Conclusion: One in five eligible Ni-Vanuatu women have undergone cervical cancer screening since 2015, with 7.6 per 1000 women having malignant results and 40.4 per 1000 women having high-grade or possible high-grade results.

  • ORIGINAL ARTICLE
    Mona A. H. Yehia, Sabah A. Al-Qadasi, Amel S. Al-Sedfy, Noura A. K. Matar
    Malignancy Spectrum, 2025, 2(1): 26-36. https://doi.org/10.1002/msp2.70000

    Background: The Fn14 fibroblast growth factor-inducible 14 (Fn14) can stimulate cell migration and promote cancer lessions. Progranulin (GP88) protein has been identified as an epidermal growth factor and participates in many biological processes. The aim of the present work was to investigate the immunohistochemical expression of Fn14 and GP88 proteins in relation to the clinical parameters in women's invasive ductal carcinoma (IDC) and to explore their role as novel prognostic biomarkers.

    Methods: The qualitative and quantitative immunohistochemical techniques were used to evaluate the expression levels of Fn14 and GP88 in 100 fresh samples of Egyptian women who had breast lesions. They were divided into three groups: control healthy tissues (10 samples from woman lesions), benign group (30 cases), and IDC group (60 cases).

    Results: The histopathological results of 60 cases with IDC have been reported with 45 cases being grade Ⅱ and 15 cases being grade Ⅲ. The immunohistochemical results showed that the degree of strong positive staining for both markers was increased in grade Ⅲ compared to that in grade Ⅱ. The integrated optical density was significantly increased in grade Ⅲ (p < 0.05). Also, the result revealed a highly significant correlation between the two markers and the tumor size, grades, and lymph node metastasis, as well as a correlation to normal and benign breast lesions.

    Conclusion: The quantitative immunohistochemistry of Fn14 and GP88 proteins revealed the correlation between the two markers and clinical parameters. Therefore, the two markers may be serviceable as prognostic and therapeutic markers in IDC patients.

  • ORIGINAL ARTICLE
    Mahdi Mohammadi, Kiana Taheri, Shamim Fooladgar, Saghar Omidvar Masoumi, Elham Tafsiri
    Malignancy Spectrum, 2025, 2(1): 37-45. https://doi.org/10.1002/msp2.70002

    Background: Lung cancer is the leading cause of cancer-related deaths worldwide. MicroRNAs (miRNAs) are small noncoding molecules that play critical roles in cell proliferation, apoptosis, invasion, and metastasis, and they can target multiple genes at the mRNA level.

    Materials and methods: Some online tools like TargetScan, miRDIP, miRmap, and miRanda were used to evaluate the validated target genes. Before choosing target genes, we took advantage of some bioinformatics tools including STRING, GeneMANIA, and TRED to predict the target genes. Finally, the expression levels of the target genes were measured in non-small cell lung cancer (NSCLC) tumor and their adjacent normal tissues via SYBR Green-based quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR).

    Results: According to bioinformatics tools, BCL2 and AKT3 were selected as target genes for miR-15/16, and BCL2 was shown to demonstrate a robust negative correlation with miR-15a in our previous analysis of NSCLC tumor samples. Furthermore, we found a significant correlation between BCL2 expression level and stage Ⅲ (p = 0.04). PTEN was assumed as a validated target gene of miR-21 that presented a significant decrease in tumor tissues compared to adjacent normal tissues. IRS1 was assigned as a target gene of miR-126/miR-128, and finally, HIF1A was selected as the target gene of miR-210. There was a significant negative association between IRS1 expression level and miR-126/miR-128, but a positive correlation was demonstrated between miR-210 and HIF1A at mRNA level.

    Conclusion: Restoration of miR-15/16, miR-126, and miR-128 in NSCLC might be therapeutic candidates to control cell proliferation and apoptosis.

  • ORIGINAL ARTICLE
    Wen Lynn Teong, Wei Yee Wong, Su Lin Lim, Choon Hui Low, Cassandra Lim Duan Qi, Ruochen Du
    Malignancy Spectrum, 2025, 2(2): 74-83. https://doi.org/10.1002/msp2.70007

    Objective: Weight loss in colorectal cancer (CRC) surgical patients is widespread and often associated with increased morbidity and mortality. This study aimed to determine whether pre-surgery nutrition intervention in CRC patients can reduce post-surgery weight loss and improve nutritional status and quality of life (QoL).

    Methods: Sixty CRC patients undergoing elective surgery from November 2018 to February 2021 were recruited. They were compared to a control group of 60 CRC patients extracted retrospectively from 2014. The intervention group received pre-surgery nutrition counselling and was followed up at 1, 2, and 3 months after surgery, where their weights were taken and nutritional status was assessed using Subjective Global Assessment (SGA). Health-related QoL was assessed using the 3-level Euro-Quality of Life 5 Domain (EQ-5D-3L) questionnaire before surgery and at 3 months after surgery. The control group did not receive pre-surgery nutrition counselling.

    Results: At 3 months after surgery, the intervention group lost significantly less weight compared to the control group (p < 0.001). Similar significant results were observed at 1 and 2 months after surgery (p < 0.001). Fifty-two patients (91%) in the control group lost weight compared to 31 patients (53%) in the intervention group at 3 months after surgery (p < 0.001). Within the intervention group, the post-surgery Quality of Life Visual Analogue Scale improved significantly from baseline (80% versus 75%, p = 0.043). The SGA score at 3 months after surgery was similar to that of baseline (p = 0.109).

    Conclusion: Pre-surgery nutrition intervention in patients with CRC and elective surgery has resulted in a significant reduction in post-surgery weight loss, improvement in QoL, and maintenance of nutritional status.

  • ORIGINAL ARTICLE
    Steffie Urmila Avanthi, Ravikanth Vishnubhotla, Mitnala Sasikala, Guduru Venkat Rao, Rebala Pradeep, Sanjeev Marigowda Patil, Anuradha Sekaran, Jain Aviral, Sonali Mondkar, Nageshwar Reddy Duvvur
    Malignancy Spectrum, 2025, 2(2): 84-94. https://doi.org/10.1002/msp2.70009

    Background: Chemotherapy is the mainstay to treat metastatic colorectal cancer (CRC). However, a sizeable proportion of patients do not respond to treatment, which leads to the recurrence of disease. This study was carried out to identify reliable gene expression-based marker(s) to predict the response to chemotherapy and the risk of recurrence.

    Methods: This prospective study involved the collection of tumor tissues (n = 100) and normal tissues (n = 10) from CRC patients who primarily underwent surgical treatment. Global gene expression profiles were generated on microarray (Affymetrix; n = 5) and the next-generation sequencing (NGS) (Illumina; n = 20) platforms. Patients were classified as responders (n = 13; complete response with no relapse) or non-responders (n = 12; recurrence of disease leading to death). Common dysregulated genes identified from both platforms were replicated in an independent set (n = 75; quantitative real-time polymerase chain reaction (qRT-PCR)). The area under the curve (AUC) was generated, and a combinatorial analysis was performed.

    Results: A total of 193 and 1351 genes were dysregulated in microarray and NGS datasets, respectively. Of the top common genes (PTGIS, LYVE1, C3, C7, CXCL12, CEACAM6, MUC13, and ST14) that were selected for replication, upregulation of five genes (PTGIS, C3, C7, LYVE1, and CXCL12) were associated with the non-responder group in validation set. Combinatorial analysis and comparison of AUC identified a significant increase (p = 0.03) in AUC by 15.2% (95% confidence interval (CI): 0.01-0.29) for two genes (PTGIS and LYVE1). Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 88.9%, 100%, 100%, and 95.6%, respectively.

    Conclusion: Assessing upregulation of the PTGIS and LYVE1 genes enables identification of individuals who may not respond to adjuvant chemotherapy and the risk of recurrence. The addition of drugs targeting these genes may improve response and benefit the patients.

  • ORIGINAL ARTICLE
    Mozaffar Aznab, Fatemeh Heydarpur, Amirmasoud Rahimi, Sayed Javad Hossini, Kiumrs Eslampia
    Malignancy Spectrum, 2025, 2(2): 95-102. https://doi.org/10.1002/msp2.70011

    Objective: Maintenance treatment with rituximab has been used in some nodal lymphomas, such as follicular and diffuse large cell lymphoma. The aim of this study was to evaluate the survival of extra nodal lymphoma patients under maintenance treatment.

    Materials and methods: From July 2008 to December 2017, after induction treatment in patients with extra nodal lymphoma, if the patients consented and the drug was available, they were treated with rituximab every 3 months for 2 years.

    Results: A total of 112 patients with extra nodal lymphoma met the inclusion criteria. Among them, 89 patients had high-grade lymphomas and 23 patients were in the group of low-grade lymphomas. The group of patients with high-grade lymphoma who received the rituximab-containing regimen as a maintenance treatment had lower rates of recurrence and death compared to the group that received rituximab only in the induction phase. In patients with low-grade lymphoma, the recurrence rate and mortality were also lower in the group receiving maintenance treatment compared to other groups, but the difference was not statistically significant.

    Conclusion: The use of rituximab in patients with extra nodal lymphoma as maintenance can increase the survival of the patients.

  • CASE REPORT
    Xueling Chen, Xuejian Ning, Tao Si
    Malignancy Spectrum, 2025, 2(2): 103-109. https://doi.org/10.1002/msp2.70006

    Objective: The incidence of primary tracheal neoplasm is extremely rare. Squamous cell carcinoma (SCC) is the most prevalent histological type of tracheal malignancy. Postoperative adjuvant radiotherapy can be considered as a curative management option. However, there are limited data available on the use of radiotherapy or concurrent chemoradiotherapy for tracheal cancer, particularly intensity-modulated radiotherapy.

    Patient and methods: Herein, we present a case report of a young adult male diagnosed with primary SCC of the trachea who underwent postoperative concurrent chemoradiotherapy utilizing intensity-modulated radiation therapy (IMRT). The treatment included 50.4 Gy radiation in 28 fractions and two cycles of chemotherapy.

    Results: The patient experienced grade Ⅰ dermatitis and grade Ⅱ granulocytosis. Follow-up showed no evidence of recurrence or significant adverse effects. The patient achieved 5-year long-term survival with good quality of life.

    Conclusion: Postoperative concurrent chemoradiotherapy using IMRT is effective for primary tracheal carcinoma, offering long-term survival and quality of life benefits.

  • CASE REPORT
    Huan Zhang, Zhao Ma, Shuwen Yang, Linqi Liu, Shu Zhou, Lanxin Feng, Ran Ran, Wenyang Liu, Chenchen Tu, Xiantao Song, Hongjia Zhang
    Malignancy Spectrum, 2025, 2(2): 110-115. https://doi.org/10.1002/msp2.70010

    Background: Breast cancer is one of the most common malignant tumors among women worldwide. Chemotherapeutic and targeted agents, as important adjuvant therapy for breast cancer, can also cause cardiotoxicity, leading to cardiac dysfunction. It is essential to recognize cardiotoxicity early, cease drug exposure when appropriate, and initiate heart failure therapy. Currently, echocardiography is routinely used to monitor cardiac function during treatment. However, normal left ventricular ejection fraction (LVEF) measured by echocardiography cannot exclude cardiotoxicity. Therefore, more sensitive cardiac monitoring tools are needed. Optical pumped magnetometer-magnetocardiography (OPM-MCG) has been proved to be a noninvasive and effective means to detect and monitor myocardial injury.

    Case description: In this case, we presented a patient diagnosed with early breast cancer with human epidermal growth factor receptor 2 (HER2) overexpression, following adjuvant therapy with paclitaxel liposomes, trastuzumab, and pertuzumab. Heart failure with reduced ejection fraction (HFrEF) occurred after five cycles of anti-HER2 therapy, which improved with chronic heart failure (CHF) treatment. The MCG scan of this patient was significantly abnormal when she developed symptomatic HFrEF, which improved gradually during CHF treatment.

    Conclusion: The patient's heart failure was most likely caused by HER2-targeted agents, which was reversible and could be improved with the administration of angiotensin receptor neprilysin inhibitor (ARNi) and sodium-glucose cotransporter-2 inhibitor (SGLT2i). In the future, OPM-MCG may act as a safe, accurate, and efficient evaluation tool for cardiotoxicity monitoring to detect early myocardial injury in cancer patients.