Radiotherapy is one of the most important therapeutic strategies for treating cancer. For decades, studies concerning the outcomes of radiotherapy mainly focused on the biological effects of radiation on tumor cells. Recently, we have increasingly recognized that the complex cellular interactions within the tumor microenvironment (TME) are closely related to treatment outcomes. As a critical component of the TME, fibroblasts participate in all stages of cancer progression. Fibroblasts are able to tolerate harsh extracellular environments, which are usually fatal to all other cells. They play pivotal roles in determining the treatment response to chemoradiotherapy. Radiotherapy activates the TME networks by inducing cycling hypoxia, modulating immune reaction, and promoting vascular regeneration, inflammation and fibrosis. While a number of studies claim that radiotherapy affects fibroblasts negatively through growth arrest and cell senescence, others argue that exposure to radiation can induce an activated phenotype in fibroblasts. These cells take an active part in constructing the tumor microenvironment by secreting cytokines and degradative enzymes. Current strategies that aim to inhibit activated fibroblasts mainly focus on four aspects: elimination, normalization, paracrine signaling blockade and extracellular matrix inhibition. This review will describe the direct cellular effects of radiotherapy on fibroblasts and the underlying genetic changes. We will also discuss the impact of fibroblasts on cancer cells during radiotherapy and the potential value of targeting fibroblasts to enhance the clinical outcome of radiotherapy. This review provides good preliminary data to elucidate the biological roles of CAFs in radiotherapy and the clinical value of targeting CAFs as a supplementary treatment to conventional radiotherapy. Further studies to validate this strategy in more physiological models may be required before clinical trial.

Background and Objectives: Radiotherapy (RT) plays an important role in the treatment for locally advanced rectal cancer patients. It can bring radio exposure together with the survival benefit. Cancer survivors are generally at an increased risk for second malignancies, and survivors receiving RT may have higher risks than survivors not receiving RT. Whether the risk of an all-site second malignancy may increase after RT is still debated. This study aims to compare the second malignancy pattern in rectal cancer survivors after RT. Materials and Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used for analysis. In total, 49,961 rectal cancer patients (20–84 years of age) were identified between 2000 and 2012 from 18 SEER registries. All patients underwent surgery. The occurrence of second malignancies diagnosed after rectal cancer diagnosis was compared in patients who received and did not receive RT. The standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) were used. SEER*Stat was used to generate the 95% CIs for the SIR statistics using the exact method. Results: Of the total 49,961 patients, 5582 developed second malignancies. For all-site second primary malignancies, the age-adjusted SIRs were 1.14 (95% CI 1.1–1.18) and 1.00 (95% CI 0.96–1.04) in the no RT and RT groups, respectively. In 23,192 patients from the surgery-only group, 2604 had second malignancies, and in 26,769 patients who received RT, 2978 developed second malignancies. With respect to every site, the risk of secondary prostate cancer was significantly lower in the RT group (SIR = 0.39, 95% CI 0.33–0.46) than that in the surgery-only group (SIR = 1.04, 95% CI 0.96–1.12). Moreover, the risk of thyroid cancer was significantly higher in the RT group (SIR = 2.80, 95% CI 2.2–3.51) than that in the surgery-only group (SIR = 1.29, 95% CI 0.99–1.66). Conclusions: RT may change the second malignancy pattern in rectal cancer survivors; the risk of prostate cancer decreased, and the risk of thyroid cancer increased most significantly.

Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy, but immune-related hypersensitivity reactions remain a clinical concern. Cadonilimab, a novel PD-1/CTLA-4 bispecific antibody, has demonstrated encouraging antitumor efficacy across various solid tumors; however, hypersensitivity or infusion-related reactions may occasionally occur.Methods: We herein report five cases of cadonilimab-induced allergic or infusion-related reactions in patients with different advanced solid tumors. Clinical manifestations ranged from mild skin rash to severe anaphylaxis with hypotension. All patients were managed promptly with individualized anti-allergic interventions, and some were able to safely continue therapy with modified infusion protocols.Results: The series emphasizes the importance of early identification and tailored management of hypersensitivity reactions during cadonilimab treatment. Additionally, a comprehensive literature review was conducted summarizing current clinical trials, case reports, and real-world evidence regarding cadonilimab’s efficacy and safety across multiple cancer types.Conclusion: Our findings highlight both the potential risks and manageable nature of cadonilimab-induced hypersensitivity, supporting its continued clinical application with appropriate monitoring and management strategies.

Immune checkpoint inhibitors have been extensively utilized in the treatment of various malignancies, with camrelizumab being one of the agents in this therapeutic class. In this study, we report for the first time a case of an allergic reaction to camrelizumab in a patient with nasopharyngeal carcinoma, who was successfully rechallenged after antiallergic treatment. The patient, a 62-year-old male, was diagnosed with advanced nasopharyngeal carcinoma, exhibiting cancer infiltration and multiple metastases. He underwent multiple cycles of therapy, tolerating camrelizumab, nab-paclitaxel, and nedaplatin (200 mg of camrelizumab every 3 weeks) without adverse reactions in the first four cycles. However, during the fifth cycle, after the intravenous infusion of camrelizumab, he experienced gradual onset of dizziness and chest tightness within 15 minutes (peripheral arterial oxygen saturation was approximately 94%, blood pressure was 76/42 mmHg, heart rate was 83 beats per minute, and respiratory rate was 15 breaths per minute). The camrelizumab infusion was immediately halted, and the patient was treated with intravenous dexamethasone (10 mg) combined with intramuscular diphenhydramine, calcium gluconate, and 500 ml of normal saline; his blood pressure gradually increased to 110/80 mmHg within 10 minutes, and pruritic erythematous macules appeared on his skin, particularly on the upper limbs. Subsequently, nab-paclitaxel was infused, and upon completion, the erythematous macules on the limbs faded. The patient was then rechallenged with a slow infusion of camrelizumab, which was well-tolerated without discomfort or a drop in blood pressure. The patient did not report significant discomfort. Although acute allergic reactions are relatively rare among immune-related adverse events, due to the widespread clinical application of camrelizumab, its potential for allergic reactions should be given high priority.

Background: Primary cutaneous apocrine carcinoma (PCAC) is a rare malignant adnexal tumor with substantial diagnostic complexity and no established systemic therapy standard for advanced disease.Evidence for endocrine therapy, targeted therapy, and immune checkpoint inhibitors is limited to small series and case reports. Case presentation: A patient presented with a pruritic erythematous plaque on the left chest wall that progressively enlarged over one year. Skin biopsy and subsequent pathology consultation demonstrated invasive adenocarcinoma involving the dermis and subcutaneous tissue. Immunohistochemistry supported PCAC (CK7+, GATA3+, AR strongly positive, and patchy GCDFP-15 positivity), and a left axillary lymph node confirmed metastatic carcinoma. Whole-body ¹⁸ F-FDG PET/CT revealed extensive metastatic disease involving multiple lymph node stations, lung, pleura, and multiple bones, precluding upfront surgery. The patient received systemic therapy with serplulimab (300 mg intravenously every 3 weeks) plus anlotinib (10 mg orally once daily, days 1–14 of a 21-day cycle) and concomitant bicalutamide (50 mg orally once daily). After two cycles, CT imaging showed partial reduction in pulmonary nodules and mediastinal lymphadenopathy, with thinning of the chest wall lesion and resolution of a small pleural effusion. Subsequent follow-up demonstrated continued clinical improvement of the chest wall lesion and sustained radiological disease control, without new rapidly progressive visceral lesions. No clinically significant adverse events or notable laboratory toxicities were observed during treatment and follow-up. Conclusion: This case illustrates a feasible combination approach for widely metastatic PCAC using PD-1 blockade, anti-angiogenic therapy, and anti-androgen treatment, with clinical and radiographic improvement and favorable tolerability during follow-up. Prospective data are needed to clarify patient selection and define optimal systemic strategies for advanced PCAC.