Combination Of Radiotherapy Research Articles

In situ enzymatic peptide-based nanomedicine with combined effects for enhanced tumor radio-immunotherapy

Despite the combination of radiotherapy and immunotherapy in clinical practice have shown promising synergistic anti-tumor effect, the immunosuppressive tumor microenvironment (TME) remains to be one of stumbling block impeding the therapeutic efficacy of radio-immunotherapy. In this study, in situ self-assembled peptide-based drug delivery systems with multiple effects were constructed for enhancing tumor radio-immunotherapy. The two peptide-drug conjugates could co-assembled into peptide-based nanomedicine on the cancer cell membrane under enzyme catalysis and continuously release small molecular active drugs in the cytoplasm, which combined action lead YAP phosphorylation and nuclear transfer failure. By simutaneously suppressing glycolysis and reactivating the dysfunctional Hippo pathway, the peptide-based nanomedicine also remitted the immunosuppressive TME by reducing lactate levels and the expression of immunosuppressive factors, respectively. As a result, the pro-tumorigenic M2 phenotype of tumor-associated macrophages (TAMs) was decreased and the anti-tumorigenic M1 phenotype of TAMs was increased. Such a dual intervention strategy from cellular metabolic level and gene transcription level not only inhibited tumor cell proliferation but also reversed the immunosuppressive TME, thereby augmenting the combined efficacy of radiotherapy and immune checkpoint blockade (ICB) therapy. The work is anticipated to contribute novel insights into anti-cancer drug targeted delivery and tumor multi-modal synergistic therapy.

23-year review of spheno-orbital meningioma: clinical, radiological, and pathological insights from 100 cases

BackgroundSpheno-orbital meningioma (SOM) represents a unique variant of sphenoid wing meningiomas, distinguished by its propensity for bone infiltration and cranio-orbital involvement. SOM exhibits a considerable incidence of misdiagnosis and recurrence.PurposesTo elucidate the clinical, radiological, and pathological characteristics of SOM.MethodsReview of electronic medical records, histopathology, radiological images and follow-up information of 100 SOM patients.ResultsOf the 100 patients (28 males, 72 females) with SOM, mean age was 46.8 ± 12.6 years and prevalent symptoms were proptosis (99%). All the CT scans showed hyperostosis with 89.3% of the hyperostosis having an irregular edge. In MRI scans, dural tail sign was observed across all patients and the cranio-orbital tumors often penetrated temporal muscle (74.1%), extraocular muscle (74.1%) and lacrimal gland (63%). All the 100 patients underwent surgical intervention, and among them, 62 individuals received postoperative radiotherapy. Grade I resections had a lower recurrence rate(16.7%), which further decreased with the addition of radiotherapy(13.9%). In contrast, all patients with grade II or higher grade resections without radiotherapy experienced recurrence, indicating a higher risk associated with less complete tumor removal. The pathological examination revealed that intraorbital sections exhibited comparable tumor density to intraorbital SOM tumors, along with increased fibrous density but decreased vascular distribution.ConclusionsRadiological characteristics of SOM included cranio-orbital tumors, hyperostosis of the sphenoid wing with an irregular edge, and dural tail sign. Combination of gross total resection and adjuvant radiotherapy was recommended to minimize recurrence rate. Intracranial SOM tumors tended to be softer and more bleed-prone than intraorbital sections, necessitating surgical precision.

A retrospective study of 96 cases of adrenal metastases

Objective: To analyze the clinical characteristics, etiological composition, imaging features, and prognosis of adrenal metastases. Methods: This study is a retrospective case series that included 96 patients with pathologically confirmed adrenal metastases who were treated at West China Hospital, Sichuan University, from 2007 to 2017. Clinical features such as sex, age, tumor size, biochemical tests, imaging characteristics, postoperative pathology, treatment methods, and prognosis were collected and analyzed. The prognosis of patients and its influencing factors were analyzed by Kaplan-Meier survival curve and single-factor Cox risk proportional model. Results: Among the 96 included patients, 64 were male and 32 were female, with a median age of 60 years. There were 89 cases of unilateral adrenal metastases, five cases of bilateral metastases, and two cases with unspecified laterality. The median diameter of the metastases was 3.5 cm×2.9 cm, with an average CT value of 31 HU. Thirty-four cases of adrenal hormones were evaluated, and no abnormality was found.The primary tumor sites were as follows: lung (n=36), kidney (n=19), liver (n=12), pancreas (n=7), rectum (n=3), stomach (n=2), and one case each of tumor in the esophagus, skin, thyroid, left maxillary muscle, breast, bladder, cervix, chest wall, and gastrointestinal tract. There were three cases with unknown primary tumors. The most common pathological type was lung adenocarcinoma (20.8%, 20/96), followed by hepatocellular carcinoma (9.4%, 9/96) and high-grade invasive urothelial carcinoma of the kidney (8.3%, 8/96). Thirty-nine cases were diagnosed concurrently with the primary tumor, while 37 cases were diagnosed after the primary tumor, with a median interval of 15 months (range: 2-144 months). There was no significant correlation between the death risk of adrenal metastatic tumor patients and gender, age, and the size of the metastatic tumor (all P>0.05). There were 4 patients with radiotherapy and chemotherapy alone, 19 patients with surgery alone, and 6 patients with combined radiotherapy and chemotherapy. The median overall survival was 1, 3, and 7 years, respectively. Conclusions: Adrenal metastases were mostly diagnosed at the same time as the primary tumor or within 15 months after the diagnosis of the primary tumor. Unilateral metastasis is common. The lungs are the most common primary lesion, followed by the kidney and liver. CT is the preferred method for the diagnosis of adrenal metastases, and the plain CT value is more than 30 HU. The overall prognosis of adrenal metastases is poor. The prognosis was better for patients who underwent surgery combined with radiotherapy and chemotherapy than those who received only surgery or radiotherapy and chemotherapy alone.

Ocular adnexal lymphoma - a retrospective study and review of the literature.

To review the characteristics of all Slovenian patients with ocular adnexal lymphoma (OAL) in the period of 24 years with the aim of evaluating demographic data, lymphoma location and type, disease stage, treatment modality, local control rate and survival rate. All patients with histologically diagnosed OAL in the main tertiary centre of Slovenia, Eye Hospital, University Medical Centre Ljubljana, who were treated at Institute of Oncology Ljubljana were included in the study. Patients' data were collected from October 1995 through April 2019. Seventy-four patients were included in the study having a median age of 68 years at diagnosis. The majority of lymphomas were of B-cell origin (98.6%). The most frequent type was the extranodal marginal zone B-cell lymphoma (MALT) (71.6%). Orbital lymphomas were diagnosed in 56 cases (75.7%) and conjunctival in 18 cases (24.3%). Ocular manifestation was the first sign of the disease in 78.4% of patients and in 67.6% of patients ocular adnexa were the only disease location. Fifty-one patients (68.9%) were treated with radiotherapy, 7 patients (9.4%) with systemic treatment, 5 patients (6.8%) with combined radiotherapy and systemic treatment and in 11 patients, biopsy and active surveillance strategy was applied (14.9%). Local control of the disease was achieved in 96.6% of treated patients. Median overall survival of the whole study group has not been reached yet. Five-year overall survival rate was 80.1% (95% CI 68.1% - 88.5%) and 5-year lymphoma specific survival rate was 87.2% (95% CI 83.2%-91.2%). OALs comprise a group of heterogeneous diseases with variable outcomes depending predominately on the patient's age and lymphoma type, with low grade lymphomas carrying good prognosis even in elderly patients.

Limb salvage using radical combined hyperthermia and radiotherapy for myxofibrosarcoma of the lower leg in an elderly patient.

Soft tissue sarcomas account for only 1.5% of malignant tumors in adults and are therefore challenging to treat. We present a case of myxofibrosarcoma of the lower leg in an 88-year-old woman who successfully responded to combined hyperthermia and radiotherapy. We proposed a below-knee amputation because of the spread of the lesion, but the patient opted for hyperthermia with radiotherapy. One and a half years later, the tumor partially regrew, and the regrown mass was resected with an R0 margin. Unfortunately, the patient developed a surgical site infection immediately after the resection, and a skin ulcer formed. It took about 2years for conservative treatment to result in complete ulcer epithelization. The patient has been ambulant, and has not experienced any symptoms of local recurrence or metastasis in the two and a half years since the surgery. Although adverse events related to combined hyperthermia and radiotherapy, such as delayed wound healing, should be considered, it could be an option for the treatment of localized soft-tissue sarcoma, especially in elderly patients.

Immunotherapeutic allogeneic dendritic cell and autologous tumor cell fusion vaccine alone or combined with radiotherapy in canine oral malignant melanoma is safe and potentially effective.

Immunotherapy represents a promising breakthrough in cancer management and is being explored in canine melanomas. Dendritic cells (DCs) play a crucial role in priming T-cell-mediated immune reactions through the antigen-presenting function. Combining immunotherapy and radiation therapy may generate more substantial anti-cancer efficacy through immunomodulation. Our research reported a preliminary result of the safety and outcome of a kind of immunotherapy, the allogeneic dendritic cell and autologous tumor cell fusion vaccine, alone or in combination with hypofractionated radiation therapy, in canine oral malignant melanoma. Two groups of dogs with histopathological diagnoses of oral malignant melanoma were recruited. In group 1 (DCRT), dogs received a combination of DC fusion vaccine and radiotherapy. In group 2 (DC), dogs received DC fusion vaccine alone. DC vaccination was given once every 2 weeks for four doses. Radiotherapy was performed weekly for five fractions. Dogs that received carboplatin were retrospectively collected as a control group (group 3). Five dogs were included in group 1 (two stage II, three stage III), 11 in group 2 (three stage I/II, eight stage III/IV), and eight (two stage I/II, six stage III/IV) in the control group. Both DC and DCRT were well-tolerated, with only mild adverse events reported, including mucositis, gastrointestinal discomfort, and injection site reactions. The median progression-free intervals in groups 1, 2, and 3 were 214 (95% CI, NA, due to insufficient data), 100 (95% CI, 27-237), and 42 days (95% CI, NA-170), respectively, which were not significantly different. The 1-year survival rates were 20, 54.5, and 12.5% in groups 1, 2, and 3. Dogs in the DCRT group exhibited significantly higher TGF-β signals than the DC group throughout the treatment course, indicating a possible higher degree of immunosuppression. The manuscript demonstrated the safety of dendritic cell/tumor cell fusion vaccine immunotherapy, alone or in combination with radiotherapy. The results support further expansion of this immunotherapy, modification of combination treatment and protocols, and investigation of combining DC vaccine with other treatment modalities. Preclinical Trials, PCTE0000475.

79. The role of combination surgery and radiotherapy in patients with metastatic spinal cord compression: what are the remaining grey areas?

79. The role of combination surgery and radiotherapy in patients with metastatic spinal cord compression: what are the remaining grey areas?

Radiosensitizing effects of CDK4/6 inhibitors in hormone receptor-positive and HER2-negative breast cancer mediated downregulation of DNA repair mechanism and NF-κB-signaling pathway

CDK4/6 inhibitors combined with endocrine therapy prolonged survival in hormone receptor (HR)-positive and HER2-negative advanced breast cancer. We investigated whether CDK4/6 inhibitors enhance radiosensitivity and their underlying mechanisms of this subtype of breast cancer. In vitro and in vivo experiments were conducted using two HR-positive and HER2-negative breast cancer cell lines (MCF-7 and T-47D), CDK4/6 inhibitors (ribociclib and palbociclib) and radiotherapy (RT) to assess the biological functions and mechanisms. The radiation-enhancing effect was assessed using clonogenic assays; γH2AX and 53BP1 levels were assessed by immunofluorescence to evaluate DNA damage. The levels of phospho (p)-ERK, c-Myc, and DNA-double strand break (DSB)-related molecules, p-DNA-PKcs, Rad51, and p-ATM, were assessed by western blotting. We used an NF-κB p65 transcription factor assay kit to evaluate NF-κB activity. We evaluated the antitumor effect of the combination of RT and ribociclib through the MCF-7 orthotopic xenograft model. The synergistic effects of combining RT with ribociclib and palbociclib pretreatment were demonstrated by clonogenic assay. CDK4/6 inhibitors synergistically increased the numbers of RT-induced γH2AX and 53BP1, downregulated the expression of p-DNA-PKcs, Rad51 and p-ATM activated by RT, and reduced RT-triggering p-ERK expression, NF-κB activation, and its down-streaming gene, c-Myc. Combined ribociclib and RT reduced the growth of MCF-7 cell xenograft tumors, and downregulated the immunohistochemical expression of p-ERK, p-NF-κB p65, and c-Myc compared to that in the control group. Combining CDK4/6 inhibitors enhanced radiosensitivity of HR-positive and HER2-negative breast cancer cells at least by reducing DNA-DSB repair and weakening the activation of ERK and NF-κB signaling by RT.

Combination of locoregional radiotherapy with a TIM-3 aptamer improves survival in diffuse midline glioma models.

Pediatric diffuse midline gliomas (DMG) with altered H3-K27M are aggressive brain tumors that arise during childhood. Despite advances in genomic knowledge and the significant number of clinical trials testing new targeted therapies, patient outcomes are still poor. Immune checkpoint blockades with small molecules, such as aptamers, are opening new therapeutic options that represent hope for this orphan disease. Here, we demonstrated that a TIM-3 aptamer (TIM-3 Apt) as monotherapy increased the immune infiltration and elicited a strong specific immune response with a tendency to improve the overall survival of treated DMG-bearing mice. Importantly, combining TIM-3 Apt with radiotherapy increased the overall median survival and led to long-term survivor mice in 2 pediatric DMG orthotopic murine models. Interestingly, TIM-3 Apt administration increased the number of myeloid populations and the proinflammatory CD8-to-Tregs ratios in the tumor microenvironment as compared with nontreated groups after radiotherapy. Importantly, the depletion of T cells led to a major loss of the therapeutic effect achieved by the combination. This work uncovers TIM-3 targeting as an immunotherapy approach to improve the radiotherapy outcome in DMGs and offers a strong foundation for propelling a phase I clinical trial using radiotherapy and TIM-3 blockade combination as a treatment for these tumors.

Antiresorptive therapy in combination with radiation results in enhanced risk for necrosis and associated complicatifions

Patients exposed to a combination of antiresorptive medication and radiotherapy of the head and neck area developing necrosis of the jaw in the course of treatment are extremely rare. Therefore the aim of this study was to identify outcome and complications in this highly vulnerable patient cohort. Patients and Methods: Seventeen patients who received both, antiresorptive treatment and radiotherapy (MRONJ/ORN-Group) in the head and neck area were enrolled in this study. Included patients were treated in our department between 2005 and 2022. 424 patients with medication-related osteonecrosis of the jaw (MRONJ-Group) and 138 patients with osteoradionecrosis of the jaw were enrolled as two control groups (ORN-Group). Demographic data, lesion localisation, date of primary diagnosis, clinical symptoms, type of therapy (surgical or non-surgical), details on antiresorptive treatment, outcome, and complications were recorded. Results: Pathological fractures, continuity resection and recurrence appear more often in patients who receive a combination of antiresorptive treatment and radiotherapy in the head and neck area compared to patients undergoing only one of these treatments. There was a statistically significant difference (p<0.001) between MRONJ/ORN-Group and MRONJ-Group and MRONJ/ORN-Group and ORN-Group considering recurrence, fracture and continuity resection. Patients with ORN combined with MRONJ have a 4-times higher risk for developing recurrence compared to patients with MRONJ and a 1.5-times higher risk for recurrence compared to patients with ORN. Jaw fracture and continuity resection appear more often in patients with MRONJ/ORN. Conclusion: Patients under antiresorptive therapy in combination with radiation therapy in the head and neck area have a higher risk for developing complications in case of osteonecrosis of the jaws. Therefore, a strict follow-up care schedule is highly recommended.

Outcome of whole brain irradiation with a dose-escalated simultaneous-integrated boost in patients with multiple large and/or diffuse brain metastases: real live data and review of the literature

BackgroundWe retrospectively investigate feasibility and safety of whole brain radiotherapy (WBRT) including a simultaneous-integrated boost technique (WBRT-SIB) in a cohort of patients with a very poor prognosis suffering from multiple and/or large brain metastases, unfavorable primary histology, poor performance status and/or symptomatic BMs.Materials and MethodsThirty-five patients with high brain tumor burden, extracranial metastases and low life-expectancy were treated with WBRT-SIB mostly with 35-42 Gy/14 fractions. All metastases were boosted in patients with up to 12 BMs. In patients with > 12 BM, large and/or small metastases in critical brain regions were boosted up to a maximum of 12 SIB volumes.ResultsThe median number of BM was 8 (range 2–45) and the median BM diameter was 12 mm (range 4–90 mm). Fifteen (43%) patients had ≥ 10 BMs and 25 patients presented with a Karnofski index ≤ 80%. Primary tumor histology was NSCLC (n = 13), SCLC (n = 11), breast cancer (n = 7), melanoma (n = 2), other (n = 2). The median iPFS was not reached, and 12- and 18-months iPFS were 75% and 50%, respectively. Overall, seven patients had intracranial progression: two patients within the SIB and WBRT area, one patient only within the SIB region and four patients had new BMs in the WBRT volume alone. The median iPFS for non-SCLC patients was 17 months and the 12- and 18-month iPFS were 56.8% and 28.4%, respectively. There was no significant OS difference between SCLC-group and non-SCLC patients (p = 0.38). Overall, median OS was 8.7 months and 1-year OS was 25%. The treatment was generally well-tolerated with no observed cases of radionecrosis.ConclusionOur WBRT-SIB approach involves a combination of whole brain radiotherapy and a simultaneous integrated boost to specific tumor volumes, and its effectiveness is compared with other treatment modalities in the literature. Further research, including prospective studies with larger patient cohorts, is necessary to validate and refine the findings.

Comprehensive assessment of pain characteristics, quality of life, and pain management in cancer patients: a multi-center cross-sectional study

IntroductionPain is the most common complaint among cancer patients, significantly impairing their health-related quality of life (HRQOL). There is limited evidence on the characteristics of pain among cancer patients in Nepal with low-resource settings.ObjectivesThe primary objective of this study was to evaluate the clinical characteristics of pain, factors influencing pain intensity, and the association of pain severity with quality of life (QoL) among cancer patients. Secondary objectives included investigating perceived barriers to pain management and medication adherence among these patients.MethodsThis multi-center, cross-sectional study enrolled adult patients (over 18 years old) with reported cancer diagnoses experiencing pain. Socio-demographic characteristics (e.g., age, gender, educational status), clinical characteristics (e.g. cancer diagnosis, staging), and pain characteristics (e.g., duration, type, location, medicines used for pain management, etc.) were recorded. Outcomes were assessed using the Numeric rating scale (NRS), Pain management Index, European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire, Barriers Questionnaire II, Medication Adherence Rating Scale, and Hospital Anxiety and Depression Scale.ResultsFour hundred and eight patients participated in the study. The mean ± SD age was 54.87 ± 15.65, with 226 patients (55.4%) being female. The most common cancer diagnoses were cervical (17.6%), lung (11.8%), and colon/rectum (12.0%) cancers. The most common pain locations were the head and neck (27.0%); a majority (55.6%) reported pain duration of more than 3 months. Nociceptive pain was reported by 42.4% of patients; the mean ± SD of NRS was 4.31 ± 2.69, with 32.4% of patients experiencing moderate pain. Patients with mixed pain type (B = 1.458, p < 0.001) or pain in multiple sites (B = 1.175, p < 0.001), lower Karnofsky Performance Status (KPS) (B = -1.308, p < 0.001), and specific cancer diagnoses such as prostate (B = -2.045, p = 0.002), pancreatic (B = 1.852, p = 0.004), oesophageal (B = 1.674, p = 0.012), and ovarian cancer (B = 1.967, p = 0.047), experienced varying degrees of increased NRS score. The combined chemotherapy and radiotherapy treatment modality was associated with a lower NRS score (B = -0.583, p = 0.017). A significant inverse relationship was observed between pain severity and global health status/QoL (B = -37.36, p < 0.001. Key barriers to pain management included moderate perceptions of physiological effects, communication issues between doctors and patients, and concerns about the harmful effects of pain medicine. The prevalence of non-adherence to pain medications was 13.97%.ConclusionIn conclusion, this study highlights the multi-faceted nature of pain management and QoL for cancer patients in Nepal with low-resource settings. These findings underscore the multifactorial nature of pain perception in cancer patients, with mixed pain types, pain in multiple sites, lower KPS, and specific cancer diagnoses, all contributing significantly to pain severity. Additionally, pain severity was associated with declining QoL. These findings contribute valuable insights into the complex aspects of cancer pain and its broader implications for the well-being of patients, offering a foundation for targeted interventions and improved pain management strategies in the context of cancer care in low-resource settings.

Combination of radiotherapy and PD-L1 blockade induces abscopal responses in EGFR-mutated lung cancer through activating CD8+ T cells

Patients with EGFR-mutated non-small cell lung cancer (NSCLC) respond poorly to immune checkpoint inhibitors (ICIs). It has been reported that the number of CD8+T cells is reduced in EGFR-mutated NSCLC. However, the extent of heterogeneity and effector function of distinct populations of CD8+T cells has not been investigated intensively. In addition, studies investigating whether a combination of radiotherapy and ICIs can improve the efficacy of ICIs in EGFR-mutated lung cancer are lacking. Single-cell RNA sequencing (scRNA-seq) was used to investigate the heterogeneity of CD8+T cell populations in EGFR-mutated NSCLC. The STING pathway was explored after hypofractionated radiation of EGFR-mutated and wild-type cells. Mice bearing LLC-19del and LLC-EGFR tumors were treated with radiotherapy plus anti-PD-L1. The scRNA-seq data showed the percentage of progenitor exhausted CD8+T cells was lower in EGFR-mutated NSCLC. In addition, CD8+T cells in EGFR-mutated NSCLC were enriched in oxidative phosphorylation. In EGFR-mutated and wild-type cells, 8 Gy × 3 increased the expression of chemokines that recruit T cells and activate the cGAS-STING pathway. In the LLC-19del and LLC-EGFR mouse model, the combination of radiation and anti-PD-L1 significantly inhibited the growth of abscopal tumors. The enhanced abscopal effect was associated with systemic CD8+T cell infiltration. This study provided an intensive understanding of the heterogeneity and effector functions of CD8+T cells in EGFR-mutated NSCLC. We showed that the combination of hypofractionated radiation and anti-PD-L1 significantly enhanced the abscopal responses in both EGFR-mutated and wild-type lung cancer by activating CD8+T cells in mice.

Treatment with autophagic inhibitors enhances oligonol‑induced apoptotic effects in nasopharyngeal carcinoma cells.

Although the combination of chemotherapy and radiotherapy has increased the survival rate of patients with nasopharyngeal carcinoma (NPC), certain patients do not respond well to the treatment and have a poor prognosis. Therefore, novel therapeutic drugs and strategies to improve prognosis of patients with NPC are required. As certain plant extracts can suppress the viability of cancer cells, the present study investigated whether oligonol, a polyphenolic compound primarily found in lychee fruit, exerts anticancer activities in NPC cells. MTT, ELISA and immunoblotting were performed to investigate cell survival, cytokeratin-18 fragment release, and the expression of apoptosis and autophagy markers, respectively. Oligonol decreased the viability of NPC-TW01 and NPC/HK1NPC cell lines. Oligonol increased the protein expression of several apoptosis markers, including cleaved caspase-8 and -3, cleaved PARP and cytokeratin 18 fragment. Moreover, it also increased expression of autophagy markers Beclin 1 and LC3-II, as well as LC3-II/LC3-I ratio in both NPC cell lines. Furthermore, treatment with autophagy inhibitors 3-methyladenine or LY294002 significantly increased oligonol-induced viability inhibition in NPC-TW01 cells. Combined treatment of oligonol + LY294002 reduced LC3-II expression and the LC3II/LC3I ratio while increasing cleaved caspase-8 and -3, cleaved PARP and cytokeratin 18 fragment expression in NPC-TW01 cells. These findings indicated autophagy inhibitors could enhance viability inhibition and apoptotic effects induced by oligonol in NPC cells.

Oncological outcomes of partial thickness calvarial resection for locally advanced scalp malignancies

ObjectiveTraditionally, locally advanced scalp malignancies have been managed through composite, full-thickness calvarial resection. The aim of this study is to explore the oncologic outcomes of partial calvarial resection for locally invasive scalp malignancies without medullary space invasion, employing a burr-down approach. Study designRetrospective case series. SettingTertiary referral center. MethodsThis study analyzed records of 26 adult patients diagnosed with scalp cancer that spread to the calvarial region. Data collected included demographics, medical history, adjuvant therapy details, imaging, surgical outcomes, and postoperative oncological results. Results26 patients with cancerous scalp lesions necessitating calvarial resection for deep margin control were identified in 22 men and 4 women. Mean age at diagnosis was 72.7 years. The most common histopathological diagnosis was Squamous cell carcinoma (n = 16). Partial removal of the calvarial lesions was achieved in all patients without any intraoperative complications. Twelve patients received adjuvant therapy consisting of the following modalities: radiation (6), chemotherapy (1), immunotherapy (1), a combination of immunotherapy and radiation (2), and a combination of chemotherapy and radiotherapy (2). There was a total of 7 recurrences: local (n = 3,11.5 %), regional (n = 3,11.5 %), distal (n = 1,3.8 %). Long term local control was achieved in (n = 23,88.4 %) of patients. The mean time of follow-up was 19.1 months, and the mean time to recurrence was 15.1 months. ConclusionPartial calvarial resection represents a viable, safe, and effective surgical technique for cancerous tissue removal, reducing risks associated with full thickness calvarial resection, and enhancing soft tissue healing when compared to the established gold standard.

Safety of combined ablative radiotherapy and immune checkpoint inhibitors in three phase I trials

BackgroundStereotactic body radiotherapy (SBRT) is safe and effective for treatment of extracranial metastatic disease, but its safety when combined with immune checkpoint inhibitors (ICI) has not yet been comprehensively reported. Here we report adverse events (AEs) associated with combined SBRT and ICI using prospectively-collected data on patients in three trials investigating multi-site SBRT combined with ICI. MethodsPatients were included from three prospective trials of ICI (pembrolizumab; nivolumab/urelumab or nivolumab/cabiralizumab; nivolumab/ipilimumab) with SBRT to 1–4 sites. AEs were recorded prospectively using the CTCAE v4.0. Survival was analyzed using Kaplan-Meier method with a 90-day landmark. Association of patient characteristics with cumulative incidence of AEs was assessed using Fine-Gray regression. Results213 patients were included, with a median follow-up of 10 months. Over the follow-up period, 50 % and 27 % of patients experienced at least one grade ≥ 2 or grade ≥ 3 AE, respectively. Cumulative incidences of grade ≥ 2 and grade ≥ 3 AEs at 6 months were 47 % and 23 %, respectively. Three grade 5 AEs rated “possibly” related to treatment occurred outside the 90-day dose-limiting toxicity window. Landmarked survival analysis of patients with or without grade ≥ 3 AEs showed no significant difference in progression-free or overall survival. Dual-agent ICI was significantly associated with grade ≥ 3 AE. ConclusionThis analysis features the largest prospectively evaluated cohort of patients treated with combination ablative SBRT and ICI to date and provides context for future trial design. We conclude that multi-site SBRT and ICI can be safely co-administered when SBRT is delivered with prioritization of normal tissue constraints.

Reduction in chemotherapy relative dose intensity decreases overall survival of neoadjuvant chemoradiotherapy in patients with locally advanced esophageal carcinoma

BackgroundMany patients undergo dose reduction or early termination of chemotherapy to reduce chemoradiotherapy-related toxicity, which may increase their risk of survival. However, this strategy may result in underdosing patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC). This study aimed to analyze the relationship between the relative dose intensity (RDI) and survival outcomes in patients with LA-ESCC.MethodsThis retrospective study assessed patients with LA-ESCC (cT2N + M0, cT3-4NanyM0) receiving neoadjuvant chemoradiotherapy (NCRT) with curative-intent esophagectomy. The patients received 2 courses of paclitaxel plus carboplatin (TC) combination radiotherapy prior to undergoing surgery. During NCRT, RDI was computed, defined as the received dose as a percentage of the standard dose, and the incidence of dose delays was estimated (≥ 7 days in any course cycle). The best RDI cutoff value (0.7) was obtained using ROC curve. The Kaplan–Meier survival curves were compared using the log-rank test, the treatment effect was measured using hazard ratios (HR) and 95% confidence intervals (CI).ResultsWe included 132 patients in this study, divided into RDI < 0.7 and RDI ≥ 0.7 groups using cut-off value of 0.7. RDI grade was an independent prognostic factor for OS. Baseline demographic and clinical characteristics were well balanced between the groups. There was no evidence that patients with RDI < 0.7 experienced less toxicity or those with RDI ≥ 0.7 resulted in more toxicity. However, patients with RDI < 0.7 who were given reduced doses had a worse overall survival [HR 0.49, 95% CI 0.27–0.88, P = 0.015]. The risk of a lower RDI increased with a longer dose delay time (P < 0.001).ConclusionThe RDI below 0.7 for avoiding chemoradiotherapy toxicity administration led to a reduction in the dose intensity of treatment and decreased overall survival.

The Clinicopathological Features and Prognoses of Lower Uterine Segment Cancer: A Retrospective, Single-Center Cohort Study.

This study used single-center data to analyze the clinicopathological features of site-specific endometrial cancer. Patients with endometrial carcinoma who had undergone surgery at Peking Union Medical College Hospital, China, between March 2016 and January 2022 were enrolled. Clinical information and pathological characteristics were summarized, and microsatellite status was analyzed using the immunohistochemical method. Patient prognoses were measured in terms of the rates of overall survival and progression-free survival. The mean patient age was 49 years (ranging: from 25 to 76 years old), and there was no difference in clinicopathological features between endometrioid and type II endometrial carcinoma in LUSC. The ER and PR expression ratios were 80.4% and 64.3%, respectively, in this LUSC cohort, and the MMR deficiency ratio was 33.9%, including 39.6% in endometrioid carcinoma and 15.4% in type II endometrial carcinoma. Combined MSH2&MSH6 loss was more common than combined MLH1&PMS2 being unexpressed (16.1% vs 12.5%), and dMMR patients differed significantly from the pMMR group in terms of vascular invasion (P=0.003). The combination of chemotherapy and radiotherapy did not provide a statistically significant improvement in prognosis compared to chemotherapy alone. The results of this study showed that LUSC patients tended to be younger and their tumors had less expression of hormone markers. The biological behavior of both endometrioid cancer and type II EC may be similar when EC occurs in this area. Furthermore, this type of tumor also showed a higher incidence of vascular invasion, and the combination of chemotherapy and radiotherapy did not provide significant improvement. Thus, successful treatment of LUSC tumors requires aggressive surgical intervention and a more effective postoperative treatment approach.

Evaluation of Single and Combined Temozolomide and Doxorubicin Treatment Responses in Low- and High-Grade Glioma In Vitro.

Astrocytoma, the most common type of glioma, can histologically be low or high grade. Treatment recommendations for astrocytic tumors are based on the histopathological and molecular phenotype. For grade 2 astrocytoma, the combination of radiotherapy and adjuvant chemotherapy with procarbazine, lomustine, and vincristine (PCV) is better than radiotherapy alone. Temozolomide (TMZ) is being increasingly recognized as a replacement for PCV in brain tumor therapy, due to the lower myelotoxicity. TMZ is currently a well-established first-line treatment for grade 3 astrocytoma, grade 4 astrocytoma, and glioblastoma and it is also sporadically used for grade 2 astrocytoma. However, TMZ faces multiple challenges such as adverse effects and drug resistance. In this study, we compared the cytotoxic effect induced by TMZ and doxorubicin (DOXO), alone and in combination, on a low-grade astrocytoma cell line (AC1B) and a high-grade glioma cell line (GB1B). We found that TMZ and DOXO, each produced a cytotoxic effect in monotherapy. GB1B cell line was more sensitive to the treatment than AC1B cells, at a 7- and 10-day exposure to the DOXO. However, when the duration of the treatment was extended to 14 days, GB1B cells became more resistant to DOXO treatment, compared to AC1B cells. Regarding the treatment with TMZ, GB1B exhibited greater resistance to TMZ compared to AC1B, across all studied intervals and the resistance to treatment of GB1B increased with longer exposure time. However, in combined therapy, the drugs did not exert a synergistic effect on any astrocytic cell line. The current data suggest that both TMZ and DOXO exhibit efficient therapeutic effects on low- and high-grade glioma cells. However, no synergistic effect was observed for combined therapy.

New Radiation Therapy Concepts in Non-Metastatic Lung Cancer

Radiotherapy plays a critical role in the management of non-metastatic lung cancer, offering curative potential and symptom relief. It serves as a primary treatment modality or adjuvant therapy post-surgery, enhancing local control and survival rates. Modern techniques like Stereotactic Body Radiotherapy (SBRT) enable precise tumor targeting, minimizing damage to healthy tissue and reducing treatment duration. The synergy between radiotherapy and systemic treatments, including immunotherapy, holds promise in improving outcomes. Immunotherapy augments the immune response against cancer cells, potentially enhancing radiotherapy's efficacy. Furthermore, radiotherapy's ability to modulate the tumor microenvironment complements the immunotherapy's mechanism of action. As a result, the combination of radiotherapy and immunotherapy may offer superior tumor control and survival benefits. Moreover, the integration of radiotherapy with surgery and chemotherapy in multidisciplinary approaches maximizes treatment efficacy while minimizing toxicity. Herein we present an overview on modern radiotherapy and potential developments in the close future.