Adjuvant Therapy Research Articles

Copper Depletion in Tumors Boosts Immunotherapy.

Copper depletion is being billed as a viable approach for cancer treatment. Vittorio and co-workers successfully demonstrated that Cuprior, an FDA-approved drug that binds with copper, effectively enhances anti-GD2 immunotherapy and improves the responses for neuroblastoma patients. These findings highlight the important role of copper chelation in modulating the tumor microenvironment. This study presented a novel approach to potentiate immunotherapies for neuroblastoma patients, warranting further investigations into copper depletion as a potential adjuvant therapy for other tumors.

Whole slide image based deep learning refines prognosis and therapeutic response evaluation in lung adenocarcinoma

Existing prognostic models are useful for estimating the prognosis of lung adenocarcinoma patients, but there remains room for improvement. In the current study, we developed a deep learning model based on histopathological images to predict the recurrence risk of lung adenocarcinoma patients. The efficiency of the model was then evaluated in independent multicenter cohorts. The model defined high- and low-risk groups successfully stratified prognosis of the entire cohort. Moreover, multivariable Cox analysis identified the model defined risk groups as an independent predictor for disease-free survival. Importantly, combining TNM stage with the established model helped to distinguish subgroups of patients with high-risk stage II and stage III disease who are highly likely to benefit from adjuvant chemotherapy. Overall, our study highlights the significant value of the constructed model to serve as a complementary biomarker for survival stratification and adjuvant therapy selection for lung adenocarcinoma patients after resection.

Neoadjuvant immunotherapy with or without chemotherapy in locally advanced oral squamous cell carcinoma: Randomized, two-arm, phase 2 trial.

Patients with locally advanced oral squamous cell carcinoma (OSCC) have poor outcomes with standard care. Neoadjuvant therapy is shown to be effective for these patients. In the randomized, two-arm, phase 2, non-comparative trial, we investigate the efficacy and safety of the neoadjuvant programmed cell death 1 (PD-1) inhibitor camrelizumab with or without docetaxel-cisplatin-5-fluorouracil (TPF) chemotherapy in patients with resectable locally advanced OSCC. Patients with stage III-IVA OSCC receive neoadjuvant therapy with three cycles of camrelizumab (arm Cam) with or without two cycles of TPF chemotherapy (arm Cam+TPF), followed by surgery and adjuvant therapy. Major pathological response (MPR) is achieved in both arm Cam (5/34, 14.7%) and arm Cam+TPF (26/34, 76.4%). With a median follow-up of 32months, the 2-year event-free survival (EFS) rate of arm Cam and Cam+TPF is 52.9% and 91.2%, respectively. This work demonstrates feasibility and safety for immunochemotherapy in the neoadjuvant setting for OSCC. This study was registered at ClinicalTrials.gov (NCT04649476).

Case report: Clonal evolution analysis of a rare case of meningioma lung metastases identifies actionable alterations in matched longitudinal tumour samples

Metastatic meningioma is rare, occurring in less than 1% of patients, and very few case studies have been reported, in particular for those that have spread to the lungs. Here we describe a rare case of metastatic meningioma to the lungs. Following a discussion at a medical oncology multi-disciplinary team meeting, whole genome sequencing was requested in November 2021 and discussed at a neurosurgical molecular tumor board in June 2022. Sequencing was performed on matched longitudinal collected samples of the primary tumor resection, the re-excised recurrent tumor after adjuvant radiation therapy, the lung metastases before treatment with sunitinib, and one paired blood sample for tumor-normal analysis. Whole genome characterization and clonal evolution analysis confirmed neurofibromatosis 2 (NF2) gene loss as the main driver of this cancer. In the same cancer clone as NF2, we identified a BRCA2 (p.E51K) mutation was present in all tumors, which may represent a potential driver event, though evidence supporting this is currently limited. Although this mutation is predicted to potentially influence homologous recombination, its clinical relevance as a biomarker for PARP inhibition remains speculative and requires further investigation. We also noted a SETD2 (p.S1885N) mutation that was present only in the recurrent tumor which was identified as a predicted biomarker of response to WEE1 inhibition. There was a stepwise increase in tumor mutational burden (TMB) from the primary meningioma to lung metastases, suggesting this patient may have been a candidate for immunotherapy.

Inavolisib: First Approval.

Inavolisib (Itovebi™) is an orally administered, phosphatidylinositol-3-kinase alpha (PI3Kα) inhibitor being developed by Genentech, a member of the Roche group, for the treatment of solid tumours. On 10 October 2024, inavolisib received its first approval in the USA in combination with palbociclib and fulvestrant for the treatment of adults with endocrine-resistant, PIK3CA-mutated, hormone receptor (HR)-positive, human epidermal growth factor 2 (HER2)-negative, locally advanced or metastatic breast cancer, as detected by an FDA-approved test, following recurrence on or after completing adjuvant endocrine therapy. In the EU and other countries worldwide, regulatory review of inavolisib is currently underway. This article summarises the milestones in the development of inavolisib leading to this first approval for endocrine-resistant, PIK3CA-mutated, HR-positive, HER2-negative, locally advanced or metastatic breast cancer.

Assessment of Opuntia ficus-indica supplementation on enhancing antioxidant levels

Opuntia ficus-indica (OFi) is a major fruit source prevalent in semiarid and arid regions across various countries worldwide. It is widely recognised for its potential health benefits; however, most studies investigating its effects have been limited to pre-clinical models, highlighting the need for further validation through clinical trials. This study aimed to evaluate the effectiveness of OFi supplementation in enhancing antioxidant levels. Fifty healthy participants, aged 18 years and older, including males and females, received a daily OFi supplement of 1500 mg for 3 months. These findings revealed a significant 48.1% increase in salivary total antioxidant capacity (TAC) (P < 0.001), indicating improved antioxidant activity. Simultaneously, oxidative stress biomarkers showed substantial reductions: malondialdehyde (MDA) decreased by 28.3%, nitrotyrosine (3-NT) decreased by 51.5%, and 8-hydroxy-2’-deoxyguanosine (8-OHdG) decreased by 59.8% (P < 0.001). Furthermore, participants reported a 20.1% improvement (P < 0.001) in Visual Analogue Scales (VAS), reflecting a notable enhancement in overall well-being. In conclusion, OFi exhibited promising efficacy in elevating antioxidant levels and mitigating oxidative stress. These findings suggest its potential as an adjuvant therapy for managing chronic conditions associated with oxidative stress.

Radiosurgery versus radiation therapy for long term local control rate of craniopharyngioma: a meta-analysis.

Craniopharyngiomas are challenging benign tumors arising from Rathke's pouch remnants, often requiring multidisciplinary management due to their proximity to critical neurovascular structures. This meta-analysis systematically compares conventional radiation therapy (RT) and stereotactic radiosurgery (RS) in treating residual or recurrent craniopharyngiomas. A comprehensive literature search identified 44 studies, including 46 reports, meeting inclusion criteria such as progression-free survival (PFS) and post-radiotherapy complications. Data extraction followed PRISMA guidelines. The pooled 5-year PFS favored RT (0.843; 95% CI: 0.767-0.898) over RS (0.680; 95% CI: 0.631-0.727), as did 10-year PFS (RT: 0.813; 95% CI: 0.683-0.888; RS: 0.553; 95% CI: 0.470-0.634). RT demonstrated mitigating tumor recurrence risks. Visual and hormonal complication rates between the modalities were comparable (visual: ~4%; hormonal: ~6%). RT consistently achieved superior long-term PFS compared to RS, reaffirming its role as the standard for adjuvant therapy in craniopharyngiomas. This analysis highlights the need for tailored treatment strategies balancing efficacy and safety, ultimately enhancing patient outcomes.

A Machine Learning Approach Using Topic Modeling to Identify and Assess Experiences of Patients With Colorectal Cancer: Explorative Study.

The rising number of cancer survivors and the shortage of health care professionals challenge the accessibility of cancer care. Health technologies are necessary for sustaining optimal patient journeys. To understand individuals' daily lives during their patient journey, qualitative studies are crucial. However, not all patients wish to share their stories with researchers. This study aims to identify and assess patient experiences on a large scale using a novel machine learning-supported approach, leveraging data from patient forums. Forum posts of patients with colorectal cancer (CRC) from the Cancer Survivors Network USA were used as the data source. Topic modeling, as a part of machine learning, was used to recognize the topic patterns in the posts. Researchers read the most relevant 50 posts on each topic, dividing them into "home" or "hospital" contexts. A patient community journey map, derived from patients stories, was developed to visually illustrate our findings. CRC medical doctors and a quality-of-life expert evaluated the identified topics of patient experience and the map. Based on 212,107 posts, 37 topics and 10 upper clusters were produced. Dominant clusters included "Daily activities while living with CRC" (38,782, 18.3%) and "Understanding treatment including alternatives and adjuvant therapy" (31,577, 14.9%). Topics related to the home context had more emotional content compared with the hospital context. The patient community journey map was constructed based on these findings. Our study highlighted the diverse concerns and experiences of patients with CRC. The more emotional content in home context discussions underscores the personal impact of CRC beyond clinical settings. Based on our study, we found that a machine learning-supported approach is a promising solution to analyze patients' experiences. The innovative application of patient community journey mapping provides a unique perspective into the challenges in patients' daily lives, which is essential for delivering appropriate support at the right moment.

Antihypertensive drug-related problems in Vietnamese ambulatory care

Evidence of antihypertensive drug-related problems (aDRP) is limited in Asian ambulatory care. To better detect aDRP without causing alert fatigue, we investigated whether adding more antihypertensive agents was associated with increasing aDRP risk and factors associated with physician acceptance of aDRP correction. We conducted a cross-sectional study targeting ambulatory prescriptions of Vietnamese patients with hypertension who either received standard therapy (using two or fewer medications, SdT) or standard plus add-on therapy (using more than two medications, SdT + add-on). Primary and secondary outcomes were number of aDRP and correction ratio of aDRP. We used multivariable Poisson regression to estimate the incidence rate ratio (IRR) and 95% confidence interval (95%CI). We analyzed 221 cases (patient age of 64.1 ± 9.0 years, 51.1% being female). On average, patients with SdT and SdT + add-on had 1.6 ± 1.3 and 1.6 ± 1.5 aDRP, respectively. Compared to the SdT group, SdT + add-on group did not have a higher number of aDRP (IRR = 1.11, 95%CI 0.87–1.43, p = 0.393) or likelihood of aDRP correction (IRR = 0.97, 95%CI 0.86–1.09, p = 0.578). We found the following factors to be associated with aDRP correction: unnecessary indication (IRR = 1.98, 95%CI 1.39–2.81, p < 0.001), missing indication (IRR = 1.93, 95%CI 1.68–2.21, p < 0.001), major-to-contraindicated drug interaction (IRR = 1.74, 95%CI 1.39–2.18, p < 0.001), adverse effects (IRR = 1.71, 95%CI 1.26–2.31, p < 0.001), nonconformity indication (IRR = 1.66, 95%CI 1.44–1.92, p < 0.001), and administration (IRR = 1.45, 95%CI 1.26–1.67, p < 0.001). In conclusion, adding antihypertensive agents was not associated with a higher number of aDRP or likelihood of aDRP corrections. Physician acceptance of aDRP corrections could be strongly related to unnecessary/missing indication, major-to-contraindicated drug interaction, and adverse effects. These findings could improve DRP alerts and maximize treatment outcomes in Asian patients with hypertension.

Multimodal treatment combining neoadjuvant therapy, laparoscopic subtotal distal pancreatectomy and adjuvant therapy for pancreatic neck-body cancer: Case series.

Pancreatic cancer involving the pancreas neck and body often invades the retroperitoneal vessels, making its radical resection challenging. Multimodal treatment strategies, including neoadjuvant therapy, surgery, and postoperative adjuvant therapy, are contributing to a paradigm shift in the treatment of pancreatic cancer. This strategy is also promising in the treatment of pancreatic neck-body cancer. To evaluate the feasibility and effectiveness of a multimodal strategy for the treatment of borderline/locally advanced pancreatic neck-body cancer. From January 2019 to December 2021, we reviewed the demographic characteristics, neoadjuvant and adjuvant treatment data, intraoperative and postoperative variables, and follow-up outcomes of patients who underwent multimodal treatment for pancreatic neck-body cancer in a prospectively collected database of our hospital. This investigation was reported in line with the Preferred Reporting of Case Series in Surgery criteria. A total of 11 patients with pancreatic neck-body cancer were included in this study, of whom 6 patients were borderline resectable and 5 were locally advanced. Through multidisciplinary team discussion, all patients received neoadjuvant therapy, of whom 8 (73%) patients achieved a partial response and 3 patients maintained stable disease. After multidisciplinary team reassessment, all patients underwent laparoscopic subtotal distal pancreatectomy and portal vein reconstruction and achieved R0 resection. Postoperatively, two patients (18%) developed ascites, and two patients (18%) developed pancreatic fistulae. The median length of stay of the patients was 11 days (range: 10-15 days). All patients received postoperative adjuvant therapy. During the follow-up, three patients experienced tumor recurrence, with a median disease-free survival time of 13.3 months and a median overall survival time of 20.5 months. A multimodal treatment strategy combining neoadjuvant therapy, laparoscopic subtotal distal pancreatectomy, and adjuvant therapy is safe and feasible in patients with pancreatic neck-body cancer.

Retraction Note: Comment on - Is add-on Bevacizumab therapy to Temozolomide and radiotherapy associated with clinical utility for newly diagnosed Glioblastoma? A systematic review and meta-analysis.

Retraction Note: Comment on - Is add-on Bevacizumab therapy to Temozolomide and radiotherapy associated with clinical utility for newly diagnosed Glioblastoma? A systematic review and meta-analysis.

P-62 A CASE OF PAPILLARY THYROID CARCINOMA WITH ISOLATED BONE METASTASES

Abstract Introduction Thyroid carcinomas constitute less than 3% of all cancers (1). Papillary thyroid carcinoma (PTC) accounts for 80% of thyroid carcinomas and generally has a good prognosis(2). Lymph node metastases are frequently observed in thyroid cancers(30-40%). However, distant metastases are quite rare(1-4%)(2). Clinical Case A 52-year-old female patient presented to the neurosurgery department due to back pain of approximately 2 months. A mass lesion was observed in the T9 vertebral body on a thoracic CT scan, which was destroying the bone structure, causing a compression fracture in the vertebra, and extending into the spinal canal. A total laminectomy of T9 vertebra and partial laminectomies of T8 and T10 vertebrae were performed. Pathology revealed strongly positive for Vimentin, TTF-1, Thyroglobulin, and Pax 8, consistent with carcinoma metastasis. It was recommended to perform a whole-body scan, primarily focusing on the thyroid gland. PET-CT, thoracic and abdominal CT scans revealed a 62x48 mm metastatic lesion in the right iliac bone and metastatic involvement of the T9 vertebra, with no other pathological findings. The patient's history revealed that she had undergone a total thyroidectomy six years ago, and the result was reported as benign. She was on levothyroxine sodium replacement therapy. Blood tests revealed TSH: 0.288 (0.27-4.2 µIU/ml), T4: 18.7 (12-22 pmol/L), T3: 4.78 (3.1-6.8 pmol/L), Anti-Thyroglobulin Antibody: 60.8 (0-115 IU/ml), and Thyroglobulin: &amp;gt;500 (3.5-77 ng/ml). Neck ultrasonography did not reveal any residual thyroid tissue or pathological lymph nodes. Given the suspicion of thyroid carcinoma metastasis and high thyroglobulin levels, the pathology preparations of the total thyroidectomy were re-consulted by our hospital's pathology department. The pathology result was consistent with papillary thyroid carcinoma composed of 55% follicular subtype and 45% solid/trabecular subtype. As surgery for the iliac bone metastasis was not considered appropriate, the patient was referred to the nuclear medicine department for radioactive iodine therapy and to the radiation oncology department for radiotherapy. The nuclear medicine, radiation oncology, and our department continue to follow up and treat the patient. Conclusion PTC is generally a slowly progressing cancer with a good prognosis. The most common site of metastasis in all PTC cases is the cervical lymph node, and only 3.5-3.8% have distant metastases(3). Distant metastases are most commonly seen in the lungs (53.4%), followed by bones (28.1%), liver (8.3%), and brain (4.7%) (1,4). Distant metastases significantly increase mortality from PTC. Therefore, the importance of adjuvant therapy (endocrine therapy, radiotherapy, etc.) and regular follow-up after thyroid cancer surgery should be emphasized. It should be kept in mind that, as in our case, papillary thyroid carcinomas can also present with isolated bone metastases without cervical lymph node metastases.

Improving predictive accuracy of early recurrence in pancreatic ductal adenocarcinoma: Role of postoperative serum tumor markers.

In a recent study by He et al, the nomogram integrates postoperative serum tumor markers such as carbohydrate antigen 19-9 and carcinoembryonic antigen, thereby improving the accuracy of identifying high-risk patients compared to relying solely on preoperative markers, which has significant implications for customizing adjuvant therapy and potentially improving outcomes for this aggressive form of cancer. However, the study's single-center design and short follow-up period may limit the generalizability of its findings and potentially introduce reporting bias. Future studies could consider additional confounding factors, such as adjuvant chemotherapy and variations in surgical techniques, to improve the model's accuracy. Furthermore, it would be valuable to validate the nomogram in broader, prospective cohorts and explore the inclusion of additional markers like circulating tumor DNA to refine further its predictive power and applicability across diverse patient populations.

Surgery for the Treatment of HPV-Negative Oropharyngeal Squamous Cell Carcinoma-A Systematic Review and Meta-Analysis.

Human papillomavirus (HPV) negative oropharyngeal squamous cell carcinoma (OPSCC) is associated with worse survival when compared to HPV-positive OPSCC. Primary surgery is one option to intensify therapy in this high-risk group of patients. Unfortunately, the only randomized trial to explore this approach (RTOG 1221) failed to accrue and the role of primary surgery in the treatment of HPV-negative OPSCC remains unanswered. A systematic review and meta-analysis were performed to examine the outcomes of surgery in the treatment of HPV-negative OPSCC. We used the PRISMA statement for reporting and queried Pubmed, Web of Science and the Cochrane databases for studies examining the use of primary surgery in the treatment of HPV-negative OPSCC. Excluded from analysis were reviews, commentaries, case series with fewer than 10 patients, and studies that included HPV-negative head and neck cancers of mixed sites. Our primary outcomes were 2-year and 5-year overall survival (OS) and disease-free survival (DFS). OS and DFS were pooled using meta-analysis of proportions. A total of 15 studies were included in qualitative synthesis and 11 were included in the meta-analysis. There were 923 patients total included. Eight studies including 483 patients reported staging of HPV negative disease, of which 81.6% had T1/T2 tumors and 41.4% had N0 nodal disease. The average rate of positive margins was 12.6%. The average rate of patients who underwent risk-stratified adjuvant RT was 30.7% and CRT was 29.5%. The average follow-up was 32.7 months (SD = 12.47 months). Only two studies reported survival outcomes for HPV-negative disease based on overall staging: 5-year OS was improved for stage III versus stage IV and early versus late stage disease. The pooled 2- and 5-year OS were 84% (95% CI 77%-91%, I2 = 52.4%; 5 studies) and 72% (95% CI 46%-92%, I2 = 95.5%; 4 studies), respectively. The pooled 2- and 5-year DFS for the entire population were 77% (95% CI 66%-86%, I2 = 55%; 6 studies) and 59% (95% CI 50%-69%, I2 = 0%; 3 studies). Of the subgroup undergoing TOS alone, the pooled 2- and 5-year OS were 87% (95% CI 79%-93%, I2 = 46.8%; 4 studies) and 82% (95% CI 69%-92%, I2 = 74.2%; 3 studies). The pooled 2- and 5-year DFS for the subgroup of patients undergoing TOS alone were 78% (95% CI 63%-90%, I2 = 56%; 4 studies) and 59% (95% CI 47%-71%, I2 = undetermined; 2 studies). The two- and five-year OS for patients with HPV-negative OPSCC treated with any surgical approach and pathology-directed adjuvant therapy is 84% and 72%, respectively. The two- and five-year OS for HPV-negative OPCSCC treated with transoral surgery and pathology-directed adjuvant therapy is 87% and 82%, respectively.

New and Emerging Biological Therapies for Myasthenia Gravis: A Focussed Review for Clinical Decision-Making.

Myasthenia gravis (MG) is a rare autoimmune disease characterised by exertion-induced muscle weakness that can lead to potentially life-threatening myasthenic crises. Detectable antibodies are directed against specific postsynaptic structures of the neuromuscular junction. MG is a chronic condition that can be improved through therapies, but to date, not cured. Standard treatment has been unchanged for decades and includes symptomatic treatment with acetylcholine-esterase inhibitors and disease-modifying treatment with steroids, steroid-sparing immunosuppressants and thymectomy. Overall, a relevant proportion of patients does not achieve a satisfactory clinical improvement under standard treatment. Additionally, long-term therapy with steroids can cause significant side effects and latency to clinical improvement with standard steroid-sparing immunosuppressants and after thymectomy can take months to years. In recent years, treatment of MG has changed fundamentally due to improved evidence from phase 3 trials and the regulatory approval of complement inhibitors and FcRn inhibitors as add-on treatment options. This provides new optimism for substantially more patients reaching minimal manifestation status and has led to a shift in treatment strategy with more targeted therapies being employed early in the course of the disease, especially in patients with high disease activity. In this focussed review, we provide an overview of the diagnosis, classification and standard treatment of MG, followed by data from randomised controlled trials on the modern drugs already available for therapy and those still in the final stages of clinical development. In the second part, we provide an overview of real-world data for already approved therapies and outline how the availability of new biologicals is changing both clinical decision-making and patient journey.

Grading systems and perineural invasion in oral squamous cell carcinoma - a disease-specific survival analysis.

Oral squamous cell carcinoma (OSCC) is an aggressive cancer, with prognosis influenced by clinical variables as well grading systems and perineural invasion (PNI), which are associated to poorer outcomes, including higher rates of recurrence and metastasis. This study aims to evaluate OSCC using three grading systems and assess the impact of PNI and clinicopathologic parameters on patient survival. Eighty-one primary OSCC samples were analyzed. Histopathological evaluations were performed utilizing Malignancy Grading of the Deep Invasive Margins, WHO grading system, and the Histologic Risk Assessment. S-100 immunohistochemistry was used to detect PNI. Five-year disease-specific survival (DSS) curves were generated using the Kaplan-Meier method, and the Cox proportional hazards model analyzed prognostic significance. Advanced clinical stage was significantly associated with reduced survival (p-value <0.001, HR = 4.07). Patients without regional lymph node involvement had better survival (p-value 0.002, HR = 0.37). Higher histologic risk assessment scores were linked to worse outcomes. Multifocal neural invasion significantly correlated with poorer survival compared to unifocal invasion (p-value 0.017, HR = 4.20). Patients undergoing surgery followed by adjuvant therapies had better survival rates. Besides clinical stage and histological grade, PNI also showed to be a crucial prognostic factor in OSCC, necessitating aggressive treatment strategies.

Abstract A014: Mitochondrial dynamics in insulin-like growth factor binding protein 3-mediated radiosensitivity of oral squamous cell carcinoma cells

Abstract Radiation therapy, a common adjuvant therapy for oral squamous cell carcinoma (OSCC) patients either received operation or not, efficiently reduces the tumor infiltration area and growth. Insulin-like growth factor binding protein 3 (IGFBP3) is a member of a secretary glycoprotein family. We previously found that IGFBP3 promotes cell migration and lymph node metastasis of OSCC cells. However, OSCC patients with high IGFBP3 expression had a better prognostic outcome than those with low IGFBP3 expression. Moreover, we verified that ectopic expression of IGFBP3 augmented the radiosensitivity, while IGFBP3 knockdown diminished the radio-resistance of OSCC cells. We observed changes in mitochondrial morphology in IGFBP3-expressing OSCC cells after ionizing radiation (IR) treatment; however, the roles of IGFBP3 in mitochondrial dynamics remain unclear. The analyses of cell survival, reactive oxygen species production, and loss of mitochondrial membrane potential were used to verify the IGFBP3-mediated radiosensitivity. Using mitochondria by 3D cell explorer and quantification of mitochondria dynamics by immunofluorescence staining, the fission and fusion mitochondria in irradiated IGFBP3-expressing cells and IGFBP3 knockdown cells were increased, respectively. By western blot, we found phosphorylated dynamin-related protein 1 (DRP1) positively associated with IGFBP3 levels in irradiated cells. By transiently expressing DRP1 in IGFBP3-expressing cells, we found that IGFBP3-mediated radiosensitivity and mitochondrial fission were flattened by DRP1 inhibition, suggesting the role of DRP1 in IGFBP3-mediated mitochondrial fission. Our study is to elucidate the mechanism of IGFBP3-mediated radiosensitivity and hope to provide different strategies to sensitize radiotherapy and enhance the synergy between radiotherapy and immunotherapy. Citation Format: Ya-Wen Chen. Mitochondrial dynamics in insulin-like growth factor binding protein 3-mediated radiosensitivity of oral squamous cell carcinoma cells. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr A014

Systematic Review of the Presentation, Treatment, and Outcome of Chronic Disseminated Candidiasis in Children with Cancer or Following Hematopoietic Cell Transplant.

Chronic disseminated candidiasis (CDC) is a rare complication of immunosuppression. This review describes the presentation, management, and outcomes of CDC in pediatric patients with cancer or following hematopoietic cell transplant (HCT). PubMed, Embase, and Medline were searched identifying 32 studies, describing 95 cases of CDC. CDC occurred almost exclusively in patients with leukemia (91%), with only 5% occurring in lymphoma, 1% post HCT, and 3% in solid tumor. The most frequent presenting symptoms were fever (97%) and abdominal pain (45%), with lesions in liver in 63% and spleen in 54% (less common in kidney, lungs and skin/soft tissue). Of the 67 (71%) episodes with microbiological confirmation, Candida tropicalis (28%) was the most common causative species. Antifungal treatment durations varied from 14days to 28months. Additionally, 31 (33%) patients received an adjuvant therapy, the most common being corticosteroids. Mortality, directly attributable to CDC, occurred in nine (9%). There remains insufficient data to guide a unified approach to management.

Prognostic factors and outcomes of adjuvant and first-line metastatic treatments in melanoma a Turkish oncology group study

Management of melanoma has changed significantly with the discovery of targeted therapies and immune checkpoint inhibitors (ICI). Our aim in the study is to determine which treatment alternatives, specifically dabrafenib plus trametinib and ICIs, are effective in adjuvant therapy and which treatment is effective as first-line metastatic therapy. This retrospective, multicenter study included 120 patients diagnosed with stage IIIB-IIID melanoma receiving both adjuvant and first-line metastatic treatment between 2007 and 2023. Data on clinicopathologic characteristics, treatment regimens and outcomes were collected. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) were analyzed. Patients treated with dabrafenib plus trametinib as adjuvant therapy had the longest relapse-free survival (RFS) (median: 8.3 months), followed by those treated with interferon (4.1 months) and nivolumab (1.9 months) (p = 0.002). Metastatically, the highest ORR was observed in patients treated with dabrafenib plus trametinib (54.5%), followed by ICI (52.0%) and chemotherapy (33.3%). Similarly, DCR was superior for dabrafenib plus trametinib (86.3%) compared to ICI (70.8%) and chemotherapy (66.6%). Median PFS was 9.7 months (95% CI 7.2–12.2 months) in the whole group. This was 14.3 months (95% CI 9.6–19.0 months) with ICI, 10.3 months (95% CI 4.2–16.4 months) with BRAF/MEK inhibitors and 6.3 months (95% CI 4.7–7.9 months) with chemotherapy, which was statistically significant (p < 0.001). Dabrafenib plus trametinib showed the longest median OS (53.5 months) in metastatic patients and was significantly better than chemotherapy (33.6 months) (p < 0.001). BRAF V600E mutation, RFS > 6 months, ORR are all independent factors for OS prognosis. In our study, dabrafenib plus trametinib combination was more effective in adjuvant treatment of melanoma, while immunotherapy was more effective in metastatic first-line treatment.

Adjuvant radiation therapy improves outcome of patients with surgical resected adrenocortical carcinoma.

Adrenocortical carcinoma (ACC) is a rare malignancy known for high rates of recurrence and poor prognosis. Previous studies revealed controversial roles of adjuvant radiation therapy (RT) in patient management. This study aimed to investigate the role of adjuvant RT in postoperative ACC patients. Patients with histologically confirmed ACC who underwent surgical resection in the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2020 were enrolled. Propensity score matching (PSM) was used to balance baseline characteristics between patients receiving adjuvant RT and patients who did not receive RT. Overall survival (OS) and recurrence-free survival (RFS) was analyzed using the Kaplan-Meir method. Risk factors associated with survival outcome was analyzed by univariate and multivariate Cox regression analyses. Subgroup analyses were stratified by European Network for the Study of Adrenal Tumors (ENSAT) disease stage or chemotherapy. A joint retrospective analysis of stage III patients was performed based on data obtained from Ruijin Hospital and MD Anderson Cancer Center. Among the 700 patients enrolled, 137 patients undergoing postoperative RT were matched with 137 patients who did not receive RT. Overall survival for patients with adjuvant RT was better than patients without RT (log-rank P = 0.015). The 3-year and 5-year OS were 55.2 and 47.1% for patients with RT, vs 42.6 and 34.0% for patients without RT. Multivariate analysis showed adjuvant RT was independently associated with lower mortality (hazard ratio [HR] 0.63, P = 0.007). Subgroup analysis stratified by disease stage demonstrated that adjuvant RT showed the most favorable effect in stage III patients (HR 0.53, P = 0.013). Furthermore, joint analysis of two centers showed a tendency of better OS and local control rate for stage III patients with mitotane plus RT than those with mitotane alone. Our study indicated that adjuvant RT was associated with improved prognosis for ACC patients, especially for patients with ENSAT stage III diseases. Integrating adjuvant RT into standard care of ACC may be considered.