A Review of Neoadjuvant Therapy and the Watch-and-Wait Protocol in Rectal Cancer: Current Evidence and Future Directions.

The treatment of rectal cancer underwent a significant change with the introduction of total mesorectal excision (TME), which substantially improved recurrence rates. However, TME is associated with complications such as fecal incontinence and poor bladder control, especially in tumors located near the anal verge. The watch-and-wait (WW) protocol has emerged as an alternative for patients achieving a clinical complete response (cCR) following neoadjuvant radiochemotherapy. This narrative review, developed according to the Scale for the Assessment of Narrative Review Articles guidelines, evaluates neoadjuvant treatments and the WW protocol for rectal cancer. Literature was sourced from the PubMed database using specific search terms related to neoadjuvant therapy and the WW protocol, resulting in 63 articles selected for discussion. Neoadjuvant treatment, including chemoradiation and short-course radiotherapy, is indicated for T3 and T4 rectal adenocarcinomas. Studies like the German Rectal Cancer Study Group and the PRODIGE 23 trial have shown the benefits of preoperative treatment, including improved disease-free survival and reduced local recurrence rates. However, challenges in adopting the WW protocol include the risk of local regrowth and distant metastasis. Immune checkpoint inhibitors have shown promise in mismatch repair-deficient patients, yet the data are insufficient to fully endorse WW for these cases. The WW protocol is viable for selected rectal cancer patients, with ongoing debates regarding criteria for inclusion. Key challenges include accurately identifying cCR and managing patients with near-complete responses. MRI and endoscopic evaluation are crucial for assessing treatment response, although achieving a pathological complete response remains uncertain. The WW strategy offers a potential organ-preserving approach in rectal cancer management but requires careful patient selection and comprehensive risk-benefit discussions. Further research is needed to refine criteria for inclusion and optimize treatment protocols, enhancing outcomes while minimizing invasive interventions.

CT-Guided Online Adaptive Stereotactic Body Radiotherapy (SBRT) for Retroperitoneal Sarcoma After Previous Radiotherapy: A Case Report.

CT-guided online adaptive radiotherapy (OART) is a novel and robust treatment technique in radiotherapy. Thanks to its excellent accommodation of inter-fraction variations, OART is characterized by superior accuracy compared to other contemporary treatment techniques in radiotherapy such as image-guided radiotherapy (IGRT). Planning target volume (PTV), which takes into account interfraction movements, could therefore be reduced while utilizing OART with a consequent dose reduction for adjacent healthy tissue. Herein we report our successful experience in treating a patient with retroperitoneal sarcoma after previous radiotherapy and surgery. The tumor was in close proximity to the spinal canal and abutted a large bowel segment and the last portions of the duodenum. Radiotherapy regimen consisted of 30 Gy in five fractions. Treatment implementation and delivery were feasible and the treatment was given without any interruptions. After a follow-up period of nine months so far, the patient reported no radiation-related adverse effects. Furthermore, her post-treatment magnetic resonance imaging (MRI) scans demonstrate good radiographic response.  Our case highlights the use of OART to treat a challenging case in radiotherapy as it was given in the setting of re-irradiation to a mesenchymal tumor, which is considered exquisitely radio-resistant.

State-of-the-art application of nanoparticles in radiotherapy: a platform for synergistic effects in cancer treatment.

Radiotherapy (RT) is a gold standard cancer treatment worldwide. However, RT has limitations and many side effects. Nanoparticles (NPs) have exclusive properties that allow them to be used in cancer therapy. Consequently, the combination of NP and RT opens up a new frontier in cancer treatment. Among NPs, gold nanoparticles (GNPs) are the most extensively studied and are considered ideal radiosensitizers for radiotherapy due to their unique physicochemical properties and high X­ray absorption. This review analyzes the various roles of NPs as radiosensitizers in radiotherapy of glioblastoma (GBS), prostate cancer, and breast cancer and summarizes recent advances. Furthermore, the underlying mechanisms of NP radiosensitization, including physical, chemical, and biological mechanisms, are discussed, which may provide new directions for next-generation GNP optimization and clinical transformation.

Impact of Various Treatment Modalities on Long-Term Quality of Life in Cervical Cancer Survivors.

Introduction Given treatment advancements and the long life expectancy of mostly young patients with cervical cancer, their post-treatment quality of life (QoL) is essential to consider. This study aimed to evaluate the long-term QoL in cervical cancer survivors treated with various approaches. Methods We conducted a cross-sectional survey-based study using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Cervical Cancer Module 24 (EORTC-QLQ-CX24) questionnaires and involved members of the online cervical cancer patient support group (01/2024-02/2024). Eligible participants were ≥18 years old, diagnosed with stage IA2-IIB cervical cancer, and had completed their treatment. Respondents were stratified into four management groups: neoadjuvant chemotherapy + surgery +/- radiation therapy (RT), surgery + RT, RT alone, and surgery alone. Results Overall, 173 patients participated: 20 (11.6%) received neoadjuvant chemotherapy + surgery +/- RT, 50 (28.9%) had surgery + RT, 69 (39.9%) had RT alone, and 34 (19.7%) had surgery alone. Patients after surgery alone had significantly better global QoL (p<0.001). Their physical (p<0.001), role (p=0.037), emotional (p=0.024), and social (p=0.006) functioning were also substantially better. This group also reported the lowest severity of fatigue (p=0.001), nausea and vomiting (p<0.001), and diarrhea (p<0.001). Sexual functioning was better in the surgery-alone group in almost all aspects. There were no major differences in QoL among the groups, receiving RT alone or combined with other treatments. Conclusions Cervical cancer survivors who underwent surgery alone reported the highest QoL and lower symptom intensity compared to those treated with RT or treatment combinations. RT combined with other modalities did not appear to substantially decrease QoL compared to RT alone.

Hemorrhagic Bullous Lichen Sclerosus of the Breast: A Rare Complication of Radiotherapy.

Cutaneous side effects from radiotherapy are commonly reported in breast cancer patients. Radiation-induced hemorrhagic bullous lichen sclerosus (RHBLS) of the breast is a rare, but important, complication of radiotherapy. RHBLS typically presents as painful, hemorrhagic bullae with surrounding sclerotic tissue. A 71-year-old female with a history of whole breast radiotherapy for invasive ductal carcinoma of the right breast and ductal carcinoma in situ (DCIS) of the left breast presented to the clinic with pruritic, firm, and erythematous plaques involving the inframammary folds that progressed into large, painful, hemorrhagic bullae surrounded by porcelain-white skin over several weeks. Biopsy was consistent with RHBLS. She was initially treated with systemic steroids and Clobetasol 0.05% ointment twice daily with partial improvement. To the best of our knowledge, only three definitive cases have been previously reported in the literature making this the fourth case.

Use of Cystourethroscopy to Define the Gross Tumour Volume in Radiation Treatment Planning for Canine Genitourinary Carcinomas.

Radiotherapy (RT) is increasingly utilised for definitive-intent treatment of canine genitourinary carcinomas (CGUC). At our institution, the standard approach is to irradiate tomographically abnormal tissues gross tumour volume (GTV) plus a clinical target volume (CTV) expansion of 2 cm. Cystourethroscopy is often incorporated into the treatment planning workflow, though an optimal approach has yet to be defined. This observational study evaluated cystourethroscopy as a tool for identifying gross lesions that can be targeted with RT. We hypothesised that in most cases, addition of cystourethroscopy would result in a larger GTV than would be drawn with computed tomography (CT) alone. Medical records from 54 dogs diagnosed with CGUC between 2013 and 2023 were reviewed; each had been evaluated before RT using CT and cystourethroscopy. The GTV was initially defined as the tomographically evident disease on a post-contrast sagittal plane CT scan, and then lesions visualised with cystourethroscopy (suspected or confirmed to be tumour) were added. Beyond what was visible on CT, cystourethroscopy extended the GTV by a median of 6.5 cm distally into the urethra (range: 1.5-31.8 cm) and therefore resulted in GTV enlargement in 26 of 54 (48%) cases. Addition of our standard 2 cm CTV expansion to a CT-defined GTV (without use of data from cystourethroscopy) would have underestimated the extent of grossly abnormal tissue in 35% (19/54) of cases. These results suggest that incorporating cystourethroscopy into treatment planning workflows may improve local tumour control by reducing the risk of a geographic miss.

Primary Neuroendocrine Carcinoma of the Ileum With Markedly Elevated Carcinoembryonic Antigen (CEA) Levels: A Case Report.

Neuroendocrine carcinomas (NECs) are rare and highly malignant tumors with a generally poor prognosis. Carcinoembryonic antigen (CEA) is often associated with adenocarcinoma, but its significant elevation in NEC cases is unusual. A 69-year-old man was admitted to our hospital in January 2016 due to syncope induced by anemia. The patient had a hemoglobin level of 8.0 g/dL and an ileocecal mass causing small bowel obstruction on computed tomography. His CEA level was markedly elevated at 3625.4 ng/mL. A colonoscopy revealed a neoplastic lesion in the terminal ileum, leading to an emergency ileocecal resection. Pathology confirmed a NEC, positive for synaptophysin and CEA, with a Ki-67 index of 30%. The patient was diagnosed with stage IIIb NEC (pT3N2M0). A postoperative increase in CEA to 4124.6 ng/mL and metastases in the right lung and multiple lymph nodes were detected. Initial chemotherapy with irinotecan, cisplatin (IP), and octreotide acetate proved ineffective. Subsequent octreoscans showed disease progression. Switching to everolimus as second-line therapy temporarily decreased CEA levels and tumor size, but the disease progressed with cervical lymph node involvement. The patient underwent palliative radiotherapy but succumbed to disease progression in May 2018, with a final CEA level of 36,643 ng/mL. Necropsy of the cervical lymph nodes was consistent with the original surgical findings. This case highlights the aggressive nature and challenging management of NEC with significantly elevated CEA levels.

Combination approach using neoadjuvant therapy with radical prostatectomy for improving oncological outcomes of high-risk prostate cancer: a narrative review.

Background and Objective: Prostate cancer (PCa) is the most common cancer in men. High-risk PCa is associated with an increased risk of PCa-related death. The combined use of androgen deprivation therapy (ADT) is essential to improve oncological outcomes in patients with high-risk PCa, and relatively long-term ADT administration is preferred when radiotherapy is performed. Meanwhile, whether neoadjuvant therapy for radical prostatectomy (RP) improves oncological outcomes remains controversial. This study aimed to review the oncological outcomes of RP in high-risk PCa and emphasize the significance of neoadjuvant therapy including neoadjuvant hormonal therapy (NHT) and neoadjuvant chemohormonal therapy (NCHT) followed by RP for managing high-risk PCa. Methods: We searched for articles published in the PubMed and Scopus databases from January 1, 2005 to March 30, 2023 using the medical subject headings (MeSH) terms: prostate cancer, prostatectomy, radiation therapy, neoadjuvant therapy, and treatment outcome. Key Content and Findings: The study on NHT before RP for high-risk PCa found that NHT was associated with reduced adverse pathological features, such as pT3, positive surgical margins (PSM), and lymph node involvement. However, despite shorter operative times and improved surgical outcomes, NHT did not significantly enhance biochemical recurrence (BCR) or other oncological outcomes. The combination therapy using ADT and androgen receptor signaling inhibitors (ARSI) showed varying results. Another investigation explored NCHT with taxane-based agents, indicating acceptable treatment benefits and improved BCR-free survival rates in high-risk PCa patients, demonstrating potential feasibility for this approach. Ongoing trials, like the PROTEUS trial, aim to further evaluate the therapeutic efficacy of neoadjuvant therapy in high-risk PCa. Conclusions: NHT for high-risk PCa does not contribute to improved oncological outcome and should not be administered easily for downstaging or PSM reduction. NHT in combination with ARSI has the potential advantage of improving the oncological outcome of high-risk PCa compared to RP alone, but the results are currently unsatisfactory, and the development of individualized treatment strategies using several different therapeutic approaches is needed.

Fabrication of a 3D-Printed Interim Bite Splint for a Hemimandibulectomy Patient: A Case Report.

Mandibular continuity defects can result in varying degrees of cosmetic disfigurement. Restoration of form and function may require surgical reconstruction of the affected area. While surgical reconstruction may improve the overall prognostic outcomes for the patient, the definitive prosthetic phase can commence only after a substantial time lag for adequate hard/soft tissue healing. This interim phase often challenges the patient's masticatory ability. The traditional reconstruction of hemimandibulectomy defects has its own limitations. This case report describes the fabrication of a 3D-printed bite splint for a patient with limited mouth opening and significant malocclusion due to surgical over-correction. The prosthesis given served as an appliance to improve the masticatory ability of the patient.

Radiation Therapy in Non-Melanoma Skin Cancers: An Italian Survey on Behalf of the Italian Association of Radiotherapy and Clinical Oncology.

AIMS: The National Palliative Care and Interventional Radiotherapy Study Groups of the Italian Association of Radiotherapy and Clinical Oncology (AIRO) carried out a survey whose aim was to obtain a "snapshot" of the real-world practice of nonmelanoma skin cancer (NMSC) treatments in Italy. MATERIALS AND METHODS: The survey was conducted on SurveyMonkey's online interface and was sent via e-mail to our society Radiation Oncologists. RESULTS: Fifty-eight Italian radiation oncologists (ROs), representing 54 centers, answered the survey. Thirteen percent of the ROs declared they treat fewer than 10 NMSC lesions annually, 36% treat between 11 and 20, and 51% treat more than 20 lesions annually. Interventional radiotherapy (IRT) was offered by 25% of the ROs, and every case was reportedly discussed by a multidisciplinary team (71%). Electrons (74%), volumetric modulated arc therapy (V-MAT) (57%), three-dimensional conformal radiotherapy (3D-CRT) (43%), and IRT (26%) were the main treatment options. With external beam radiotherapy (EBRT), 46 and 53 different RT schedules were treated for curative and palliative intent, respectively; whereas for IRT, there were 21 and 7 for curative and palliative intent, respectively. The most popular EBRT curative options were 50-70.95/22-35 fractions (fx) and 50-70 Gy/16-20fx and for EBRT palliative settings, 30Gy/10fx, and 20-35Gy/5fx. For IRT, the most popular curative options were 32-50Gy/8-10fx and 30-54Gy/3-5fx, whereas 30Gy/6fz was the palliative option. Less than 10 re-RT cases were reported in one year in 42.5%, 11-20 cases in 42.5%, and >20 cases annually in 15%. Electrons (61%), VMAT (49%), and BRT (25%) were the most widely used approaches: 20-40Gy in 10fx and 20-25Gy in 5fx were the recommended fractionations. CONCLUSION: The survey shows a variegated reality. A national registry with more detailed data could help in undercover its causes.

Tumor cell-intrinsic MELK enhanced CCL2-dependent immunosuppression to exacerbate hepatocarcinogenesis and confer resistance of HCC to radiotherapy.

BACKGROUND: The outcome of hepatocellular carcinoma (HCC) is limited by its complex molecular characteristics and changeable tumor microenvironment (TME). Here we focused on elucidating the functional consequences of Maternal embryonic leucine zipper kinase (MELK) in the tumorigenesis, progression and metastasis of HCC, and exploring the effect of MELK on immune cell regulation in the TME, meanwhile clarifying the corresponding signaling networks. METHODS: Bioinformatic analysis was used to validate the prognostic value of MELK for HCC. Murine xenograft assays and HCC lung metastasis mouse model confirmed the role of MELK in tumorigenesis and metastasis in HCC. Luciferase assays, RNA sequencing, immunopurification-mass spectrometry (IP-MS) and coimmunoprecipitation (CoIP) were applied to explore the upstream regulators, downstream essential molecules and corresponding mechanisms of MELK in HCC. RESULTS: We confirmed MELK to be a reliable prognostic factor of HCC and identified MELK as an effective candidate in facilitating the tumorigenesis, progression, and metastasis of HCC; the effects of MELK depended on the targeted regulation of the upstream factor miR-505-3p and interaction with STAT3, which induced STAT3 phosphorylation and increased the expression of its target gene CCL2 in HCC. In addition, we confirmed that tumor cell-intrinsic MELK inhibition is beneficial in stimulating M1 macrophage polarization, hindering M2 macrophage polarization and inducing CD8 + T-cell recruitment, which are dependent on the alteration of CCL2 expression. Importantly, MELK inhibition amplified RT-related immune effects, thereby synergizing with RT to exert substantial antitumor effects. OTS167, an inhibitor of MELK, was also proven to effectively impair the growth and progression of HCC and exert a superior antitumor effect in combination with radiotherapy (RT). CONCLUSIONS: Altogether, our findings highlight the functional role of MELK as a promising target in molecular therapy and in the combination of RT therapy to improve antitumor effect for HCC.

Efficacy of chemoradiotherapy in elderly patients with stage IV inoperable head and neck cancer.

OBJECTIVES: This study aimed to compare the efficacy of chemoradiotherapy (CRT) with radiotherapy (RT) alone for elderly patients (≥ 65 years) with stage IV inoperable head and neck cancer (IV-HNC). METHODS: Elderly patients diagnosed with inoperable IV-HNC from 2010 to 2015 were identified using the SEER database. Then, we performed a 1:1 propensity-score matched (PSM) analysis to reduce treatment selection bias, and the prognostic role of CRT was investigated using Kaplan-Meier analysis, log-rank test, and Cox proportional hazard models. The main outcome was overall survival (OS), and the secondary outcome was cancer-specific survival (CSS). RESULTS: A total of 3318 patients were enrolled, of whom 601 received RT alone and 2717 received CRT. Through PSM, 526 patients were successfully matched, and balances between the two treatment groups were reached. In the matched dataset, multivariable Cox analysis revealed that CRT was associated with better OS (HR = 0.580, P < 0.001) and CSS (HR = 0.586, P < 0.001). Meanwhile, subgroups of patients with IV-HNC (younger age, male sex, being married, black race, grade I-II, oral cavity site, T3-T4 stage, N0-N1 stage, M1 stage) were inclined to benefit more from CRT treatment. Furthermore, the survival benefit of CRT was more pronounced in patients aged 65 to 80 years, but was absent in patients aged 80 years or older. CONCLUSIONS: This study indicated that CRT resulted in better survival than RT alone in elderly patients with inoperable IV-HNC, especially for those subpopulations that benefit more from CRT treatment.

The impact of different modalities of chemoradiation therapy and chemotherapy regimens on lymphopenia in patients with locally advanced non-small cell lung cancer.

Background: Chemotherapy and radiotherapy (RT) would induce lymphopenia, leading to a poor prognosis. This study investigated whether chemotherapy increased lymphopenia during RT and explored the impacts of different chemotherapy regimens on the lymphocyte counts of patients receiving RT. Methods: Clinical parameters and lymphocyte data were collected from 215 patients with locally advanced non-small cell lung cancer (LA-NSCLC). Severe lymphopenia (SRL) was defined as an absolute lymphocyte count (ALC) of ≤0.2×103 cells/µL. Patient overall survival (OS) was analyzed using the Kaplan-Meier method. The predictors of SRL were extracted using univariate and multivariate regression analyses with backward likelihood ratio elimination. Results: Compared with patients without SRL, patients with SRL with LA-NSCLC showed a poorer prognosis in terms of OS (P=0.003). Of the 215 patients, 130 underwent concurrent chemoradiotherapy (CCRT) and 85 underwent sequential chemoradiotherapy (SCRT). The OS was better in patients without SRL (in the CCRT group, P=0.01 and in the SCRT group, P=0.08). The mean ALCs for CCRT and SCRT did not differ significantly (P=0.27). The minimum ALC of CCRT was significantly lower than that of SCRT (P<0.0001). CCRT was a predictor of SRL (P=0.008). However, multivariate analysis showed that the different chemotherapy regimens were not predictors of SRL (all P>0.1). Conclusions: In LA-NSCLC, the outcomes of patients with SRL were poorer than those without SRL. RT and chemotherapy were the main factors affecting SRL development, while different chemotherapy regimens were not significantly associated with lymphocyte counts in LA-NSCLC.

Prevention of cardiotoxicity in childhood cancer survivors: In physical exercise, we trust.

In recent years, the mean survival rate of children after a cancer diagnosis has significantly improved. At the same time, a growing interest in short and long-term cardiovascular (CV) complications of cancer therapy, as well as long-term CV risk in childhood cancer survivors (CCS) developed, along with proposals of protocols for the diagnosis, management, and prevention of cancer therapy-related CV toxicity (CTR-CVT) in this population. Many clinical and individual risk factors for CTR-CVT have been identified, and a non-negligible prevalence of traditional CV risk factors has been described in this population, potentially associated with a further worsening in both CTR-CVT and long-term CV risk. Physical exercise (PE) represents a promising, free-of-cost and free-of-complications, helpful therapy for primary and secondary prevention of CTR-CVT in CCS. The present narrative review aims to summarize the most critical evidence available about CTR-CVT in CCS, focusing on the role of PE in this clinical scenario.

Type I interferon signaling promotes radioresistance in head and neck cancer.

Despite the promise of concurrent radiotherapy (RT) and immunotherapy in head and neck cancer (HNC), multiple randomized trials of this combination have had disappointing results. To evaluate potential immunologic mechanisms of RT resistance, we compared pre-treatment HNCs that developed RT resistance to a matched cohort that achieved curative status. Gene set enrichment analysis demonstrated that a pre-treatment pro-immunogenic tumor microenvironment (TME), including type II interferon [interferon gamma (IFNγ)] and tumor necrosis factor alpha (TNFα) signaling, predicted cure while type I interferon [interferon alpha (IFNα)] enrichment was associated with an immunosuppressive TME found in tumors that went on to recur. We then used immune deconvolution of RNA sequencing datasets to evaluate immunologic cell subset enrichment. This identified M2 macrophage signaling associated with type I IFN pathway expression in RT-recurrent disease. To further dissect mechanism, we then evaluated differential gene expression between pre-treatment and RT-resistant HNCs from sampled from the same patients at the same anatomical location in the oral cavity. Here, recurrent samples exhibited upregulation of type I IFN-stimulated genes (ISGs) including members of the IFN-induced protein with tetratricopeptide repeats (IFIT) and IFN-induced transmembrane (IFITM) gene families. While several ISGs were upregulated in each recurrent cancer, IFIT2 was significantly upregulated in all recurrent tumors when compared with the matched pre-RT specimens. Based on these observations, we hypothesized sustained type I IFN signaling through ISGs, such as IFIT2, may suppress the intra-tumoral immune response thereby promoting radiation resistance.

Interpretable deep learning insights: Unveiling the role of 1 Gy volume on lymphopenia after radiotherapy in breast cancer.

BACKGROUND: Lymphopenia is known for its significance on poor survivals in breast cancer patients. Considering full dosimetric data, this study aimed to develop and validate predictive models for lymphopenia after radiotherapy (RT) in breast cancer. MATERIAL AND METHODS: Patients with breast cancer treated with adjuvant RT were eligible in this multicenter study. The study endpoint was lympopenia, defined as the reduction in absolute lymphocytes and graded lymphopenia after RT. The dose-volume histogram (DVH) data of related critical structures and clinical factors were taken into account for the development of dense neural network (DNN) predictive models. The developed DNN models were validated using external patient cohorts. RESULTS: A total of 918 consecutive patients with invasive breast cancer enrolled. The training, testing, and external validating datasets consisted of 589, 203, and 126 patients, respectively. Treatment volumes at nearly all dose levels of the DVH were significant predictors for lymphopenia following RT, including volumes at very low-dose 1 Gy (V1) of organs at risk (OARs) including lung, heart and body, especially ipsilateral-lung V1. A final DNN model, combining full DVH dosimetric parameters of OARs and three key clinical factors, achieved a predictive accuracy of 75 % or higher. CONCLUSION: This study demonstrated and externally validated the significance of full dosimetric data, particularly the volume of low dose at as low as 1 Gy of critical structures on lymphopenia after radiation in patients with breast cancer. The significance of V1 deserves special attention, as modern VMAT RT technology often has a relatively high value of this parameter. Further study is warranted for RT plan optimization.

Primary Mediastinal Dysgerminoma: A Case Report and Literature Review.

Germ cell tumors are malignant tumors that mostly develop in the gonads. Extragonadal localization is rare and may affect the mediastinal and sacrococcygeal regions. Mediastinal seminoma is a malignant germ cell tumor of the mediastinum. The tumor typically occurs in the anterosuperior mediastinum in males and often has a very slow growth pattern and limited potential for metastasis. And symptoms are not very characteristic, with many patients being asymptomatic and the tumor being discovered incidentally. In this paper, we report the case of a 26-year-old patient admitted for the management of a large anterosuperior mediastinal tumor encasing the vital structures of the mediastinum.

Safety and tolerability of radiotherapy in combination with systemic targeted therapies for treatment of hepatocellular carcinoma: a narrative review.

BACKGROUND AND OBJECTIVE: Palliative radiotherapy (RT) and systemic immuno- or targeted therapy both play significant roles in the treatment of advanced hepatocellular carcinoma (HCC). Concurrent application of these therapies is increasing, however, no guidelines exist regarding the combination of systemic therapy with RT. This narrative review summarises the existing literature reporting toxicity observed after concurrent treatment with RT and immuno- or targeted therapeutic agents commonly used in HCC. METHODS: The PubMed database was searched for studies published between 2011 and 2023 reporting toxicity data on patients treated concurrently with RT and targeted agents used in HCC. Due to the paucity of relevant literature in HCC, the inclusion criteria were expanded to include non-HCC cohorts treated with targeted therapies commonly used in advanced HCC. KEY CONTENT AND FINDINGS: Sixty-seven articles were included in this review. Twenty-two articles reported combined RT with sorafenib, one with regorafenib, 22 with bevacizumab, three with lenvatinib and 19 with immune checkpoint inhibitors. Significant findings include a high rate severe hepatotoxicity with combination RT and sorafenib, ranging from 0-19% with liver stereotactic body radiotherapy (SBRT) and 3-18% with conventionally fractionated liver RT. Severe gastrointestinal (GI) toxicities including perforation and ulceration were seen with combination bevacizumab and RT, ranging from 0-27% in the acute setting and 0-23% in the late setting. The safety profile of combination immune checkpoint blockade agents and RT was similar to that seen in monotherapy. CONCLUSIONS: Existing data suggests that combination RT and targeted therapy given the risk of severe adverse events including hepatotoxicity and GI toxicity. There is an urgent need for future studies specifically examining the impact of combination therapy in HCC patients to guide clinical decision-making in the evolving landscape of immune- and targeted therapies.

A Case of High-Dose-Rate Brachytherapy Under Endoscopic Retrograde Cholangiopancreatography (ERCP) for Intraductal Papillary Neoplasm of the Bile Duct.

Intraductal papillary neoplasm of the bile duct (IPNB) represents a relatively nascent pathological entity, recognized as a precancerous condition within the spectrum of cholangiocarcinoma. Surgical intervention is advocated for all patients with IPNB due to their susceptibility toward obstructive jaundice, cholangitis, and the heightened likelihood of malignant transformation. Nonetheless, the efficacy of radiation therapy for IPNB cases that are either inoperable or refractory remains inadequately substantiated. Herein, we present a case study of an IPNB patient who declined surgery, and a commendable local control was accomplished solely through the implementation of brachytherapy utilizing Ir-192. A septuagenarian Japanese man presented at our medical institution with the chief complaint of jaundice and was subsequently diagnosed with IPNB. The IPNB lesion extensively spanned from the lower intrapancreatic bile duct to the right (extending to B5/B8) and left bile ducts (up to just before B4). The patient underwent weekly endoscopic retrograde cholangiopancreatography (ERCP) sessions. The prescribed treatment regimen encompassed 36 Gy/6 Fr high-dose-rate brachytherapy (HDR-BT) administered once per week during ERCP, with each treatment session adhering to a timeframe not exceeding two hours. Two months following the initiation of treatment, a biliary endoscopy demonstrated complete resolution of the tumor lesion and amelioration of jaundice. The only observed acute adverse event was grade 2 hepatic dysfunctions. To the best of our knowledge, this represents the first documented instance of HDR-BT employed in IPNB management, suggesting its potential as a viable alternative for inoperable or refractory IPNB cases.

Global research trends in Total Body Irradiation: a bibliometric analysis.

Objectives: This manuscript presents a bibliometric and visualization analysis of Total Body Irradiation (TBI) research, aiming to elucidate trends, gaps, and future directions in the field. This study aims to provide a comprehensive overview of the global research landscape of TBI, highlighting its key contributions, evolving trends, and potential areas for future exploration. Methods: The data for this study were extracted from the Web of Science Core Collection (WoSCC), encompassing articles published up to May 2023. The analysis included original studies, abstracts, and review articles focusing on TBI-related research. Bibliometric indicators such as total publications (TP), total citations (TC), and citations per publication (C/P) were utilized to assess the research output and impact. Visualization tools such as VOS Viewer were employed for thematic mapping and to illustrate international collaboration networks. Results: The analysis revealed a substantial body of literature, with 7,315 articles published by 2,650 institutions involving, 13,979 authors. Full-length articles were predominant, highlighting their central role in the dissemination of TBI research. The authorship pattern indicated a diverse range of scholarly influences, with both established and emerging researchers contributing significantly. The USA led in global contributions, with significant international collaborations observed. Recent research trends have focused on refining TBI treatment techniques, investigating long-term patient effects, and advancing dosimetry and biomarker studies for radiation exposure assessments. Conclusions: TBI research exhibits a dynamic and multifaceted landscape, driven by global collaboration and innovation. It highlights the clinical challenges of TBI, such as its adverse effects and the need for tailored treatments in pediatric cases. Crucially, the study also acknowledges the fundamental science underpinning TBI, including its effects on inflammatory and apoptotic pathways, DNA damage, and the varied sensitivity of cells and tissues. This dual focus enhances our understanding of TBI, guiding future research toward innovative solutions and comprehensive care.