Early prediction of radiation response by imaging is a dynamic field of research and it can be obtained using a variety of noninvasive magnetic resonance imaging methods. Recently, intravoxel incoherent motion (IVIM) has gained interest in cancer imaging. IVIM carries both diffusion and perfusion information, making it a promising tool to assess tumor response. Here, we briefly introduced the basics of IVIM, reviewed existing studies of IVIM in various type of tumors during radiotherapy in order to show whether IVIM is a useful technique for an early assessment of radiation response. 31/40 studies reported an increase of IVIM parameters during radiotherapy compared to baseline. In 27 studies, this increase was higher in patients with good response to radiotherapy. Future directions including implementation of IVIM on MR-Linac and its limitation are discussed. Obtaining new radiologic biomarkers of radiotherapy response could open the way for a more personalized, biology-guided radiation therapy.

The management of cancer with alternative approaches is a matter of clinical interest worldwide. High-intensity focused ultrasound (HIFU) surgery is a noninvasive technique performed under US or MRI guidance. The most studied therapeutic uses of HIFU involve thermal tissue ablation, demonstrating both palliative and curative potential. However, concurrent mechanical bioeffects also provide opportunities in terms of augmented drug delivery and immunosensitization. The safety and efficacy of HIFU integration with current cancer treatment strategies are being actively investigated in managing primary and secondary tumors, including cancers of the breast, prostate, pancreas, liver, kidney, and bone. Current primary HIFU indications are pain palliation, complete ablation of localized earlystage tumors, or debulking of unresectable late-stage cancers. This review presents the latest HIFU applications, from investigational to clinically approved, in the field of tumor ablation. Keywords: Ultrasound, Ultrasound-High Intensity Focused (HIFU), Interventional-MSK, Interventional-Body, Oncology, Technology Assessment, Tumor Response, MR Imaging © RSNA, 2023.

OBJECTIVE: To describe different ocular paraneoplastic syndromes in patients treated with Immune Checkpoint Inhibitors (ICI), its relation with different types of ICI and different types of tumors, and its implications for treatment.
METHODS: A comprehensive review of the literature was performed.
RESULTS: Patients treated with ICI can present with different ocular paraneoplastic syndromes, such as Carcinoma Associated Retinopathy (CAR), Melanoma Associated Retinopathy (MAR) and paraneoplastic Acute Exudative Polymorphous Vitelliform Maculopathy (pAEPVM). In literature, the different types of paraneoplastic retinopathy are mostly related to different types of primary tumors, with MAR and pAEPVM seen in melanoma, and CAR in carcinoma. Visual prognosis is limited in MAR and CAR.
CONCLUSIONS: Paraneoplastic disorders result from an antitumor immune response against a shared autoantigen between the tumor and ocular tissue. ICI enhance the antitumor immune response, which can lead to increased cross-reaction against ocular structures and unmasking of a predisposed paraneoplastic syndrome. Different types of primary tumors are related to different cross-reactive antibodies. Therefore, the different types of paraneoplastic syndromes are related to different types of primary tumors and are probably unrelated to the type of ICI. ICI-related paraneoplastic syndromes often lead to an ethical dilemma. Continuation of ICI treatment can lead to irreversible visual loss in MAR and CAR. In these cases overall survival must be weighed against quality of life. In pAEPVM however, the vitelliform lesions can disappear with tumor control, which may involve continuation of ICI.

UNASSIGNED: Neoadjuvant therapy plays an increasingly important role in pancreatic neuroendocrine neoplasms (pNENs), but the systematic evaluation of its efficacy is still lacking. The purpose of this study is to explore the role of neoadjuvant therapy in pNENs.
UNASSIGNED: We systematically reviewed the literatures published online until October 1, 2021. Meta-analysis was conducted to generate proportion with 95% confidence intervals (95% CI) for tumor response, resection rate, R0 resection rate and survival time.
UNASSIGNED: Nine studies with 468 patients were involved in the systematic review. None of these patients met complete response (CR). Furthermore, 43.6% (95% CI [18.1, 69.0]) patients were expected to achieve partial response (PR), 51.3% (95% CI [27.9, 78.3]) to stable disease (SD), and 4.3% (95% CI [0.7, 7.9]) to progressive disease (PD). The estimate resection rate and R0 resection rate after neoadjuvant therapy were 68.2% (95% CI [44.5, 91.9]) and 60.2% (95% CI [53.5, 66.9]), respectively. There was no significant difference in resection rate between different chemotherapy regimens (41.67% vs 33.93%, P=0.453), as well as R0 resection rate (62.50% vs 68.30%, P=0.605). In terms of objective response rate (ORR), there was no significant difference between CAPTEM and FAS (41.67% vs 33.93%, P=0.453), while PRRT showed a higher ORR compared with chemotherapy, although there was also no statistical difference (49.06% vs 36.96%, P=0.154).
UNASSIGNED: Neoadjuvant therapies could reduce the tumor size and stage of some borderline resectable or unresectable pNENs, and give some patients the chance of radical resection. However, according to the current data, the best treatment regimen for pNENs neoadjuvant therapy is still unknown.

Introduction: The incidence and mortality of gastric cancer ranks among the highest, and the 5-year survival rate of advanced gastric cancer (AGC) is less than 10%. Currently, chemotherapy is the main treatment for AGC, and oxaliplatin is an important part of the commonly used chemotherapy regimen for AGC. A large number of RCTs have shown that Chinese herbal medicine (CHM) combined with oxaliplatin-based chemotherapy can improve objective response rate (ORR) and disease control rate (DCR), reduce the toxic and side effects of chemotherapy. There is currently a lack of systematic evaluation of the evidence to account for the efficacy and safety of CHM combined with oxaliplatin-based chemotherapy in AGC. Therefore, we carried out this study and conducted the sensitivity analysis on the herbal composition to explore the potential anti-tumor efficacy. Methods: Databases of PubMed, EMBASE, CENTRAL, Web of Science, the Chinese Biomedical Literature Database, the China National Knowledge Infrastructure, the Wanfang database, and the Chinese Scientific Journals Database were searched from their inception to April 2022. RCTs evaluating the efficacy of CHM combined with oxaliplatin-based chemotherapy on AGC were included. Stata 16 was used for data synthesis, RoB 2 for quality evaluation of included RCTs, and GRADE for quality of synthesized evidence. Additional sensitivity analysis was performed to explore the potential anti-tumor effects of single herbs and combination of herbs. Results: Forty trials involving 3,029 participants were included. Most included RCTs were assessed as \"Some concerns\" of risk of bias. Meta-analyses showed that compare to oxaliplatin-based chemotherapy alone, that CHM combined with oxaliplatin-based chemotherapy could increase the objective response rate (ORR) by 35% [risk ratio (RR) = 1.35, 95% confidence intervals (CI) (1.25, 1.45)], and disease control rate (DCR) by 12% [RR = 1.12, 95% CI (1.08, 1.16)]. Subgroup analysis showed that compare to SOX, FOLFOX, and XELOX regimens alone, CHM plus SOX, CHM plus FOLFOX, and CHM plus XELOX could significantly increase the ORR and DCR. Sensitivity analysis identified seven herbs of Astragalus, Liquorice, Poria, Largehead Atractylodes, Chinese Angelica, Codonopsis, and Tangerine Peel with potentials to improve tumor response of oxaliplatin-based chemotherapy in AGC. Conclusion: Synthesized evidence showed moderate certainty that CHM plus oxaliplatin-based chemotherapy may promote improvement in tumor response in AGC. CHM treatment is safe for AGC. Due to the poor quality of included RCTs and small samplesizes, the quality of synthesized evidence was not high. Specific combinations of herbs appeared to produce higher contributions to ORR than the herb individually. Each of this seven above mentioned herbs has been shown in experimental studies to potentially contribute to the improvement of tumor response. To support this conclusion, these seven herbs are worthy of further clinical research. Systematic Review Registration: [http://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=262595], identifier [CRD42022262595].

Although various therapies are available for the treatment of metastatic colorectal cancer (mCRC), there is lack of head-to-head evidence. Recent studies have demonstrated the efficacy of chemotherapy in combination with different biological agents including regorafenib in second-line therapy in patients with mCRC. We conducted a network meta-analysis (NMA) to estimate the relative efficacy and safety of regorafenib in combination with chemotherapy compared to other biological agents with chemotherapy combinations.
A literature search was conducted in PubMed, Embase, and Cochrane databases to identify all randomized controlled trials (RCTs) evaluating the efficacy and safety of bevacizumab, regorafenib, panitumumab, cetuximab, ramucirumab, conatumumab, ganitumab, and aflibercept in combination with chemotherapy against chemotherapy alone as second-line setting from inception to 7 February 2019 in patients with mCRC. The survival outcomes were analyzed by the frequentist statistical approach (R software, netmeta package) while the level of individual treatment arms was assessed using the Bayesian method (R software, gemtc package).
We identified 12 articles involving eight RCTs studies analyzing 6805 patients. The studies compared bevacizumab (3), regorafenib (1), panitumumab (2), cetuximab (3), ramucirumab (1), conatumumab (1), ganitumab (1), and aflibercept (1) against chemotherapy alone as comparator. The progression-free survival (PFS) revealed that regorafenib performed better than aflibercept (HR 0.9631, 95% CI 0.6785-1.367), ganitumab (HR 0.7228, 95% CI 0.3985-1.3109), panitumumab (HR 0.9653, 95% CI 0.6781-1.3742), and ramucirumab (HR 0.9206, 95% CI 0.6504-1.303). Regorafenib performed better than bevacizumab (OR 0.797, 95% CI 0.328-1.88) in terms of tumor response. Safety analysis showed that regorafenib performed better in reducing grade ≥ 3 adverse events (AE) than cetuximab and conatumumab, neutropenia than conatumumab, and fatigue than cetuximab.
Regorafenib combined with chemotherapy might be a potential alternative to conventional therapeutic options in second-line treatment of patients with metastatic colorectal cancer and could be considered as the best option for treating patients with KRAS and BRAF mutated mCRC. However future RCTs are needed to confirm these results.

BACKGROUND: Currently, nivolumab and ipilimumab are the most widely used immune checkpoint inhibitors. We performed a meta-analysis to evaluate the efficacy and treatment-related adverse events (TRAEs) of nivolumab plus ipilimumab therapy in cancer treatment.
METHODS: We examined data from PubMed, Web of Science, EBSCO, and Cochrane Library. Eleven articles fulfilled our criteria, which we divided into 3 groups: nivolumab plus ipilimumab versus nivolumab (the dose used for monotherapy is 3 mg/kg), nivolumab plus ipilimumab versus ipilimumab (the dose used for monotherapy is 3 mg/kg), and nivolumab 1 mg/kg plus ipilimumab 3 mg/kg (N1I3) versus nivolumab 3 mg/kg plus ipilimumab 1 mg/kg (N3I1). We measured the complete response (CR), partial response (PR), objective response rate (ORR), and TRAEs in any grade and grade 3 or higher.
RESULTS: The overall effect estimate favored the combined immunotherapy group in terms of the ORR (RR: 1.40, p < 0.001) and PR (RR: 1.50, p < 0.001) than nivolumab alone. Compared with ipilimumab alone, the combined immunotherapy group had better CR (RR: 4.89, p < 0.001), PR (RR: 2.75, p < 0.001), and ORR (RR: 3.31, p < 0.001). Finally, N1I3 showed better PR (RR: 1.35, p = 0.006) and ORR (RR: 1.21, p = 0.03) than N3I1. The incidence of any TRAEs was similar between both groups (RR: 1.05, p = 0.06). However, the incidence of serious adverse events (grade 3 or higher) was lower in group N3I1 than group N1I3 (RR: 1.51, p < 0.001).
CONCLUSIONS: This meta-analysis showed that the curative effect of nivolumab plus ipilimumab was better than that of nivolumab or ipilimumab monotherapy. In the combined immunotherapy group, N1I3 was more effective than N3I1. Although the side effects were slightly increased in N1I3 group, overall safety was acceptable.

This meta-analysis was designed to compare the efficacy and safety of gemcitabine-based regimens for the treatment advanced breast cancer (ABC). Altogether 15 studies involving 8195 ABC patients were retrieved for analysis. Compared with non-gemcitabine-based chemotherapies, patients receiving gemcitabine-based therapy exhibited better overall survival (OS), progression free survival (PFS), and objective response rate (ORR) (HR = 1.12, 95% CI 1.05 to 1.19; HR = 1.16, 95% CI 1.03 to 1.30; HR = 1.14, 95% CI 1.04 to 1.24). Grade 3/4 hematologic toxicity was significantly high but manageable in gemcitabine-based groups. Subgroup analysis revealed that patients with first-line gemcitabine-based chemotherapy had better OS (HR = 1.19, 95% CI 1.07 to 1.32), PFS (HR = 1.17, 95% CI 1.08 to 1.27), and ORR (RR = 1.16, 95% CI 1.02 to 1.32). In addition, additional gemcitabine chemotherapy also showed better OS (HR = 1.17, 95% CI 1.06 to 1.30), PFS (HR = 1.20, 95% CI 1.11 to 1.30) and ORR (RR = 1.23, 95% CI 1.06 to 1.42) than gemcitabine replacement therapy. Furthermore, patients receiving gemcitabine-taxanes-based regimens had better OS (HR = 1.17, 95% CI 1.06 to 1.28), PFS (HR = 1.12, 95% CI 1.04 to 1.20) and ORR (RR = 1.17, 95% CI 1.01 to 1.35) than patients with non-gemcitabine-taxanes-based chemotherapy. These findings indicate that gemcitabine combination regimens could serve as a promising regimen for ABC patients, though increased hematologic toxicity should be considered with caution.

Topotecan (TPT), a chemotherapeutic agent, is a topoisomerase-I inhibitor. Topoisomerase-I is a nuclear enzyme that relieves torsion strain in DNA by opening single strand breaks which helps in DNA replication. TPT inhibits this enzyme, thus preventing DNA replication and causes cell death. TPT has demonstrated to have broad spectrum of antitumor activity in tumors like cervical, ovarian, endometrial and small cell lung cancers (SCLCs). The intravenous (IV) formulation of the drug is currently approved by the US Food and Drug Administration for the treatment of patients with SCLC and ovarian cancer at a dose of 1.5 mg/m2 administered daily for five consecutive days, with treatment cycles repeated every 3 weeks. TPT has shown some promising activity in the treatment of non-small cell lung cancer (NSCLC) with favorable side effect profile. Several clinical trials have been conducted with TPT in either IV or oral formulation for the treatment of NSCLC as a first or second-line treatment. Here we reviewed all the clinical trials done with TPT to date in the treatment of NSCLC both as a single-agent and combination therapy.

OBJECTIVE: The EORTC PET criteria (EORTC criteria) are used to assess metabolic tumor response in patients with solid tumors. We conducted this pooled study to compare tumor responses according to the RECIST and EORTC criteria.
METHODS: Electronic databases were searched for eligible articles with the terms of \"RECIST\" or \"EORTC criteria\". We found seven articles with the data on the comparison of tumor responses by the RECIST and EORTC criteria.
RESULTS: A total of 181 patients were recruited from the seven studies. Ninety-two patients (50.8%) received cytotoxic chemotherapy and 89 were treated with targeted agents. The agreement of tumor responses between the RECIST and EORTC criteria was moderate (k = 0.493). Of 181 patients, 66 (36.5%) showed disagreement in the tumor responses: tumor response was upgraded in 54 patients and downgraded in 12 when adopting the EORTC criteria. The estimated overall response rates were significantly different between the two criteria (52.5% by the EORTC vs. 29.8% by the RECIST, P < 0.0001). When comparing the two criteria according to the anti-cancer treatments (chemotherapy or targeted therapy), the levels of agreement in tumor responses were not excellent (k = 0.461 for chemotherapy and k = 0.524 for targeted therapy, respectively) regardless of therapeutic types.
CONCLUSIONS: This pooled study indicates that the concordance of tumor responses between the RECIST and EORTC criteria is not excellent. When adopting the EORTC criteria instead of the RECIST, the overall response rate was significantly increased.