This retrospective, multicenter cohort study aimed to determine whether cancer cachexia serves as a biomarker for determining the most effective treatment for patients having non-small-cell lung cancer (NSCLC) with high programmed death ligand 1 (PD-L1) expression treated with immune checkpoint inhibitors (ICIs) alone or combined with chemotherapy (ICI/chemotherapy). We included 411 patients with advanced NSCLC with a PD-L1 tumor proportion score of ≥50%. The patients were treated with pembrolizumab monotherapy or ICI/chemotherapy. Cancer cachexia was defined as a weight loss of >5% of the total body weight or a body mass index of <20 kg/m2 coupled with an additional weight loss of >2% within 6 months before starting treatment. Eighty-five (21%) patients met the cancer cachexia criteria. Overall survival (OS) was significantly shorter in patients with cachexia than in those without cachexia in both the pembrolizumab monotherapy group (17.2 vs. 35.8 months, p < 0.001) and the ICI/chemotherapy group (27.0 months vs. not reached, p = 0.044). However, after stratifying by cancer cachexia status, no significant difference in OS was observed between the pembrolizumab monotherapy and chemoimmunotherapy groups, regardless of cachexia. In conclusion, ICI/chemotherapy offers limited benefits for NSCLC patients with high PD-L1 expression and concurrent cancer cachexia. Considering the frailty associated with cachexia, ICI monotherapy may be preferred to ICI/chemotherapy for these patients. New interventions that can better address the negative prognostic impact of cachexia in patients treated using ICIs with or without chemotherapy remain warranted.

Immune checkpoint blockers have substantially improved prognosis of melanoma patients, nevertheless, resistance remains a significant problem. Here, intrinsic and extrinsic factors in the tumor microenvironment are discussed, including the expression of alternative immune checkpoints such as lymphocyte activation gene 3 (LAG-3) and T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3). While most studies focus on immune cell expression of these proteins, we investigated their melanoma cell intrinsic expression by immunohistochemistry in melanoma metastases of 60 patients treated with anti-programmed cell death protein 1 (PD-1) and/or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) therapy, and correlated it with the expression of potential ligands, RNA sequencing data and clinical outcome. LAG-3 and TIM-3 were commonly expressed in melanoma cells. In the stage IV cohort, expression of LAG-3 was associated with M1 stage (p < 0.001) and previous exposure to immune checkpoint inhibitors (p = 0.029). Moreover, in the anti-PD-1 monotherapy treatment group patients with high LAG-3 expression by tumor cells tended to have a shorter progression-free survival (p = 0.088), whereas high expression of TIM-3 was associated with a significantly longer overall survival (p = 0.007). In conclusion, we provide a systematic analysis of melanoma cell intrinsic LAG-3 and TIM-3 expression, highlighting potential implications of their expression on patient survival.

Hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin plus raltitrexed showed a promising response rate in patients with unresectable hepatocellular carcinoma (HCC) in a phase 2 trial. Here, we report the updated 3-year survival data after enrollment.

In this prospective trial, we enrolled patients with intermediate and advanced unresectable HCC. The treatment was HAIC with raltitrexed plus oxaliplatin.

The objective responses were achieved in 19 (48.7%) of 39 patients in the intention-to-treat population. The median overall survival and progress-free survival were 11.2 and 6.5 months, respectively.

The 3-year survival update confirmed the antitumor activity and long-term survival benefit of HAIC with oxaliplatin plus raltitrexed in patients with unresectable HCC.

www.chictr.org.cn identifier is ChiCTR-OOC-17014182.

Cavitary retinoblastoma (CRB) represents a unique variant of retinoblastoma (RB) distinguished by the presence of translucent cavities, which are discernible through ophthalmoscopic examination. The present study was designed to elucidate the clinical implications and molecular signatures of CRB, thereby enhancing our understanding of this distinct subtype of RB.

A multicentric, nested case-control, retrospective cohort study combining spatial proteomic analysis.

In a longitudinal study encompassing 1360 RB patients, conducted over a 13-year timeframe from June 2008 to February 2022, cavitary spaces were detected within the tumors of 48 eyes of 46 patients. A control cohort of 180 eyes from 138 age-matched patients with non-CRB was selected, maintaining a 1:3 case-control ratio. Laser-captured spatial proteomic analysis was conducted to explore the pivotal molecular changes within this specific subtype. The silencing of MYCN was achieved using adeno-associated virus (AAV) 2-mediated gene therapy in patient-derived xenograft models.

Enucleation, chemotherapy, and focal therapy.

Overall survival and metastasis-free survival.

Cavitary RB was linked to enhanced metastasis-free survival (P = 0.007) and overall survival (P = 0.03), as well as an increased proportion of well-differentiated status (P < 0.001) and a reduced incidence of vitreous seeding (P = 0.02). Spatial proteomic analysis, immunofluorescence, and immunohistopathology revealed a lower MYCN expression in CRB than in non-CRB. Silencing MYCN in patient-derived xenografts using AAV recapitulated these phenotypes of CRB, including the formation of translucent cavities and the emergence of cone-like rosettes.

This study establishes a novel genetic-phenotypic association, revealing that diminished MYCN expression induces the formation of translucent cavities. This phenotype is indicative of a less aggressive, well-differentiated CRB subtype with a more favorable prognosis.

The author(s) have no proprietary or commercial interest in any materials discussed in this article.

The use of Immune checkpoint inhibitors (ICIs) as monotherapy for patients with hepatocellular carcinoma (HCC) has been associated with an increased risk of hyperprogressive disease (HPD), the occurrence of which carries a poor prognosis. However, it is unknown whether contemporary frontline treatment with the combination of atezolizumab and bevacizumab causes significant HPD. This study conducted a secondary analysis of patient-level data from the IMbrave150 randomized controlled trial of atezolizumab plus bevacizumab versus sorafenib for frontline treatment of HCC. Multiple established definitions of early progression and treatment failure applicable to clinical trials were evaluated, including Response Evaluation Criteria in Solid Tumours (RECIST) HPD, HPD based on percent change of sum of longest diameter (SLD HPD), treatment failure HPD (TF HPD), and fast progression (FP). The incidence of these measures was compared between arms. The risk factors for and prognosis of TF HPD were evaluated. The risk of RECIST HPD and TF HPD was significantly lower with atezolizumab plus bevacizumab treatment than with sorafenib treatment-odds ratio for RECIST HPD: 0.29 (95% CI 0.01 to 0.82), TF HPD: 0.30 (0.17, 0.54). TF HPD was similarly associated with poor prognosis, irrespective of treatment arm. High blood alpha-fetoprotein and neutrophil-to-lymphocyte ratio were both associated with an increased risk of TF HPD. For all definitions of early progression/treatment failure, the risk was either significantly lower with atezolizumab plus bevacizumab than with sorafenib, or there were no differences. Atezolizumab plus bevacizumab treatment is unlikely to cause significant HPD.

An understanding the natural history of von Hippel-Lindau (VHL) disease-associated renal cell carcinoma (RCC) is critical to the development of optimal clinical management approaches and interpretation of trial results for comparable populations and endpoints. Our aim was to describe the natural progression of disease in patients with VHL RCC.

This was a natural history study involving 244 patients with VHL with ≥10-mm renal tumor(s) who were evaluated and managed at the US National Cancer Institute between 2004 and 2020. We analyzed radiographic outcomes, renal surgeries, metastasis, sequalae of surgery, including chronic kidney disease (CKD), and mortality. Radiographic outcomes were assessed according to Response Evaluation Criteria in Solid Tumours v1.1. The primary analyses were descriptive in nature.

Among 178 patients with at least three serial tumor assessments and up to 5 yr of follow-up, the rate of spontaneous tumor regression (≥30% decrease) was 1.8% (95% confidence interval [CI] 0.4-5.2%). The probability of not having disease progression in the presence of competing risks at 5 yr was 37% (95% CI 30-44%). During follow-up, 186/244 patients had one or more renal surgeries, and 108/244 had two or more. RCC metastasis was reported for 12 patients. Among patients who underwent surgery, 41% developed postprocedure CKD. Potential limitations include selection bias and misclassification of outcomes.

Our study demonstrates that RCC is a significant burden for VHL patients, with high rates of disease progression, surgery, and metastasis development, even in a closely monitored, multidisciplinary clinical environment, and identifies CKD as an underappreciated aspect of VHL. These findings can provide a context for the antitumor activity of new treatments for RCC.

Neoadjuvant endocrine therapy (NET) in oestrogen receptor-positive /HER2-negative breast cancer (ER+/HER2- BC) allows real-time evaluation of treatment sensitivity by monitoring tumour response and offers the opportunity of personalised therapy. However, the lack of reproducible biomarkers to assess response and long-term prognosis after NET is a significant barrier to increase its indications.

In this study we searched for clinically relevant molecular reporters of response to NET in a multicentre population of ER+/HER2- BC patients (n = 87) by using: PAM50 gene expression panel and immunohistochemical evaluation of key proteins involved in tumorigenesis.

Our PAM50 analyses show that tumours changing from luminal A to normal-like subtype after NET presented better radiological and pathological tumour responses, a significant larger decrease in Ki67 at surgery, lower preoperative endocrine prognostic index score (PEPI) and lower tumour cellularity size (TCS) than those with persistent luminal A status. Patients with the highest response to NET showed the largest decrease in PAM50-derived risk of recurrence (ROR) following NET. In addition, the percentage of p53 positive cells was associated with decreased response to NET.

Our findings highlight the change of intrinsic subtype from luminal A to normal-like after NET as a putative biomarker characterising the patient population that obtains the highest benefit from NET. Our study also suggests that changes in PAM50-derived ROR score and p53 evaluation could also help to identify those patients. Thus, this study uncovers potential biomarkers of response to NET and prognosis, which should be validated in independent cohorts, helping to the implementation of NET in the clinical practice.

Lung cancer is the most common and deadly cancer worldwide. The 9th edition of the tumor node meta (TNM) classification system, effective from January 1, 2025, introduces significant updates. Notably, the N2 category is newly divided into N2a (single-station involvement) and N2b (multiple-station involvement), which reflects distinct prognostic implications. Additionally, the M1c category is now subcategorized into M1c1 (multiple metastases in a single organ system) and M1c2 (metastases in multiple organ systems), affecting stage classification. This reclassification allows for potential downstaging, which could expand treatment options for affected patients. Accurate imaging remains crucial for the classification of anatomical stages. As the TNM system evolves, enhanced imaging precision will play a key role in implementing these updates and ultimately improve patient outcomes. KEY POINTS: Question The 9th TNM for lung cancer introduces changes in the N2 and M1c descriptors, to better align with new therapeutic options and outcome studies. Findings Proper knowledge of the key changes of the 9th TNM can help radiologists offer clinicians a meaningful report. Clinical relevance Radiologists should incorporate the 9th TNM classification into their reports and discussions in multidisciplinary meetings, thus ensuring a common language across disciplines to enable clearer communication with other specialists, supporting more precise and cohesive decision-making in patient care.

Neoadjuvant immunotherapy has shown promising short-term outcomes of perioperative treatments for resectable non-small cell lung cancer (NSCLC) and is expected to release long-term survival benefits. Here, we reported the long-term prognostic value of 18F-FDG PET/CT over ∼a 5-year follow-up.

A total of 35 patients with NSCLC (29 males and 6 females; median age, 62 y) received 2 doses of sintilimab, followed by complete tumor resection and PET/CT scans at baseline and post-neoadjuvant stages. We investigated the prognostic value of PET/CT for overall survival (OS) and progression-free survival (PFS), focusing on metabolic parameters of primary tumors, mediastinal lymph nodes, lymphoid organs, and immune-related adverse events on imaging.

During a median follow-up of 62.6 months, patients with low primary tumor metabolism (SULmax ≤6.6, SULpeak ≤4.0/3.9, or SULmean ≤2.7) at post-neoadjuvant scan were alive and disease-free, demonstrating improved OS (P = 0.07, 0.07, and 0.09) and significantly enhanced PFS (P = 0.01, 0.02, and 0.02); those with low metabolic tumor volume ≤49.3 or total lesion glycolysis ≤41.0 at post-neoadjuvant scan also had significantly improved OS (P = 0.03 and 0.05). Patients with low lymph node metabolism (SULmax ≤4.6) at baseline scan had significantly improved PFS (P = 0.04).

This is the first study to report the long-term prognostic value of 18F-FDG PET/CT for resectable NSCLC after neoadjuvant immunotherapy. Low primary tumor metabolism at post-neoadjuvant scan and low lymph node metabolism at baseline scan are promising prognostic markers for improved clinical outcomes.

Prophylactic cerebral irradiation (PCI) reduces the rate of brain metastasis and improves the prognosis of patients with small cell lung cancer (SCLC), but little is known about the effect of PCI on second-line chemotherapy in patients with relapsed sensitive SCLC. This retrospective cohort study included a total of 164 patients with relapsed sensitive SCLC, 20 of whom were administered temozolomide (TMZ). Categorical clinical variables were compared between subgroups with the chi-square test or Fisher's exact test, continuous clinical variables were compared with the t-test or one-way ANOVA, and the impact on overall survival (OS) was assessed using Kaplan-Meier analysis with the log-rank test. In general, TMZ prolonged the OS of patients with SCLC with brain metastasis from 12.0 to 19.0 months [P=0.0109, hazard ratio (HR): 0.4789, 95% CI: 0.2470-0.9287]. Furthermore, the administration of PCI improved the effects of TMZ on patients with SCLC with brain metastasis, with an increase in OS from 16.0 to 36.5 months (P=0.0017, HR: 3.634, 95% CI: 1.083-12.20); additionally, no difference was observed on the basis of the history of chemotherapy or state of brain metastasis. For the local response evaluation, the overall response rate reached 75.0% for both brain metastasis and extracranial lesions in the two-cycle evaluation, remained at 30.0 and 25.0% in the four-cycle and more-cycle evaluations, respectively, and was minimally influenced by the history of chemotherapy or PCI. In conclusion, the results of this study suggest that PCI may be valuable for patients with relapsed sensitive SCLC with brain metastasis who are receiving TMZ treatment, and it may also serve as an effective regimen to prevent local progression of extracranial lesions; however, more evidence is needed.

Osteosarcoma is a highly malignant bone tumor that predominantly affects adolescents. Its aggressive nature, complex treatment options and poor prognosis render it a notable concern in oncology. With advancements in therapy for osteosarcoma, neoadjuvant chemotherapy in conjunction with limb-salvage surgery has emerged as the preferred surgical strategy. However, the physical and emotional trauma associated with surgery, along with the adverse side effects of chemotherapy, can be unacceptable to some patients. In recent years, alternative local treatment modalities such as transarterial chemoembolization (TACE) and iodine-125 seed implantation have garnered considerable attention. These techniques show potential in enhancing local tumor control while minimizing systemic toxicity. TACE involves obstructing the blood supply to the tumor while administering localized chemotherapy, resulting in tumor ischemia and necrosis, which is particularly effective for hypervascular tumors. Meanwhile, iodine-125 seeds act as low-energy radiation sources that can effectively target tumor cells while sparing the surrounding healthy tissue. The present study describes a case of osteosarcoma treated with a combination of TACE and iodine-125 seed implantation. The patient, diagnosed with osteosarcoma of the left knee joint, declined surgical intervention. Consequently, a treatment plan involving TACE paired with iodine-125 seed implantation was established. Post-treatment follow-up demonstrated marked pain relief, improved limb function and a notable reduction in tumor volume with decreased bone destruction visible on imaging. Over a follow-up period of 6 years, there were no signs of disease recurrence or distant metastasis, and no notable chemotherapy-related side effects were reported. The quality of life of the patient was markedly improved. The current case illustrates the antitumor efficacy and reduced toxicity of combining TACE with iodine-125 seed implantation in the management of osteosarcoma.

Metastatic uveal melanoma (mUM) has a poor prognosis, with liver metastases typically presenting a therapeutic challenge. Melphalan/Hepatic Delivery System (Melphalan/HDS) is a drug/medical device combination used for liver-directed treatment of unresectable mUM patients. This study assessed efficacy and safety of Melphalan/HDS versus best alternative care (BAC).

Eligible patients with unresectable mUM were randomized (1:1) to receive Melphalan/HDS (3 mg/kg ideal body weight) once every 6 to 8 weeks for a maximum of 6 cycles or BAC. Due to slow enrollment and patient reluctance to receive BAC treatment, the study design was amended to a single-arm Melphalan/HDS study, and all efficacy analyses of the randomized study were treated as exploratory.

The study enrolled 85 patients. Eligible patients were randomized to receive Melphalan/HDS (n = 43) or BAC (n = 42), and 72 patients received study treatment (Melphalan/HDS [n = 40]; BAC [n = 32]). Exploratory analyses of efficacy endpoints showed numerical differences consistently favoring the Melphalan/HDS arm versus BAC (median overall survival: 18.5 vs. 14.5 months; median progression-free survival: 9.1 vs. 3.3 months; objective response rate: 27.5% vs. 9.4%; and disease control rate: 80.0% vs. 46.9%). Serious adverse events (SAEs) occurred in 51.2% of Melphalan/HDS and in 21.9% of BAC patients. The most common (>5%) SAEs included thrombocytopenia (19.5%), neutropenia (9.8%), leukopenia (9.8%) and febrile neutropenia (7.3%) in Melphalan/HDS patients and cholecystitis, nausea and vomiting (6.3% each) in BAC patients. No treatment-related deaths were observed.

Treatment with Melphalan/HDS shows clinically meaningful efficacy and demonstrates a favorable benefit-risk profile in patients with unresectable mUM as compared to BAC.

Comsplete resection is the primary treatment for retroperitoneal sarcomas (RPS). The role of neoadjuvant chemotherapy (NACT) in improving oncologic outcomes is currently under investigation in the STRASS 2 trial. This study assessed the association between change in tumor size or pathologic response and oncologic outcomes.

Data were retrieved from the international Retroperitoneal Sarcoma Registry and included patients who had RPS treated with NACT between January 2017 and October 2020. The correlation between radiologic response (RECIST1.1), change in tumor size, pathologic response, and oncologic outcomes was evaluated. Binary logistic, Cox, and polynomial spline regression and log-rank tests were performed as statistical analyses.

The study enrolled 141 patients from 14 medical centers. The most common histologies were dedifferentiated liposarcoma (36.9 %) and leiomyosarcoma (34 %). At completion of NACT, 14.5 % of the patients, had a partial response (PR), 63.3 % had stable disease (SD), and 22.2 % had progressive disease (PD). The hazard ratio of PD after NACT for overall survival (OS) was 1.9 (95 % confidence interval [CI], 0.9-4.1). A linear trend was observed between tumor growth and death rate. At early radiologic evaluation during NACT, PD was significantly associated, with worse OS (HR, 5.4; 95 % CI, 1.1-25.3). Partial response was significantly correlated with ≥20 % fibrosis/hyalinization (odds ratio [OR], 5.6; 95 % CI, 1.1-29.0).

Progression in RPS on an early evaluation scan is associated with worse OS, and radiologic response is correlated with pathologic response based on fibrosis/hyalinization. A larger cohort is necessary for more significant associations between radiologic or pathologic response and oncologic outcomes.

To investigate overall survival (OS) and health-related quality of life (HRQOL) of first-line isolated hepatic perfusion (IHP) compared to best alternative care for patients with uveal melanoma liver metastases.

Approximately half of the patients with uveal melanoma develop metastatic disease, most commonly in the liver, and systemic treatment options are limited. IHP is a locoregional therapy with high response rates but with an unclear effect on OS.

In this phase III randomized controlled multicenter trial (the SCANDIUM trial), patients with previously untreated isolated uveal melanoma liver metastases were included between 2013 and 2021, with at least 24 months of follow-up. The planned accrual was 90 patients randomized 1:1 to receive a one-time treatment with IHP or best alternative care. Crossover to IHP was not allowed. The primary endpoint was the 24-month OS rate, with the hypothesis of a treatment effect leading to a 50% OS rate in the IHP group compared to 20% in the control group. HRQOL was measured by the EuroQol 5-domains 3-levels (EQ-5D-3L) questionnaire over 12 months.

The intention-to-treat population included 87 patients randomized to the IHP group [43 patients; 41 (89%) received IHP] or the control group (44 patients). The control group received chemotherapy (49%), immunotherapy (39%), or localized interventions (9%). In the intention-to-treat population, the median progression-free survival was 7.4 months in the IHP group compared with 3.3 months in the control group, with a hazard ratio of 0.21 (95% CI, 0.12-0.36). The 24-month OS rate was 46.5% in the IHP group versus 29.5% in the control group ( P =0.12). The median OS was 21.7 months versus 17.6 months, with a hazard ratio of 0.64 (95% CI, 0.37-1.10). EQ-5D-3L showed a sustained high health status for the IHP group over 12 months, compared to a deteriorating trend in the control group.

For patients with liver metastases from uveal melanoma, IHP offers high response rates translating to a benefit in progression-free survival including a trend of better HRQOL compared to the control group. However, the primary endpoint of OS at 24 months was not met.

Early response of the primary tumor (PT) to neoadjuvant chemotherapy (NAC) in patients with esophageal squamous cell carcinoma (ESCC) is considered a potential predictor of postoperative prognosis. However, the role of metastatic lymph nodes (LNs) remains poorly understood. This study aimed to compare the predictive value of early response in PT and LNs for postoperative prognosis.

We enrolled 124 consecutive patients who received NAC-docetaxel, cisplatin, 5-fluorouracil (DCF) followed by surgery for ESCC between April 2010 and March 2020. Initial tumor reduction of the PT (ITR-PT) and LN (ITR-LN), defined as the percentage decrease in tumor shorter diameter after the first course of NAC-DCF, was evaluated using computed tomography. The optimal cut-off values of ITRs were determined using receiver operating characteristic curves and Cox regression models, and their relationship with recurrence-free survival (RFS) was analyzed.

The median ITR-PT and ITR-LN were 21.77% and -0.88%, respectively. The optimal cut-off values for predicting prognosis were approximately 10% for ITR-PT (hazard ratio [HR], 3.23; 95% confidence interval [CI], 1.84-5.64) and -10% for ITR-LN (HR, 2.20; 95% CI, 1.27-3.80). ITR-PT showed a greater impact on RFS (3-year RFS: ITR-PT ≥ 10%, 66.1%; ITR-PT < 10%, 18.4%; log-rank P < 0.001) compared with ITR-LN (3-year RFS: ITR-LN ≥ -10%, 64.1%; ITR-PT < -10%, 34.3%; log-rank P = 0.004). Multivariate analysis of RFS identified ypN, ITR-PT, and ITR-LN as independent prognostic factors.

Both ITR-PT and ITR-LN are promising predictors of survival in patients with ESCC who underwent NAC-DCF plus surgery. ITR-PT may be a stronger prognostic factor than ITR-LN.

Desmoplastic small round cell tumor (DSRCT) is a rare, aggressive pediatric sarcoma that has a poor prognosis despite a multimodal approach of surgical resection, chemotherapy, and radiation. Incidence is only approximately 0.2 cases per million, limiting clinical trials from which to derive a standard of treatment. Advancement instead relies on case reports and series. The Children's Hospital at Montefiore in the Bronx, New York, a tertiary care hospital associated with the Montefiore Einstein Comprehensive Cancer Center, has treated eight such patients in the last decade, resulting in one of the largest single-institution case series of DSRCT patients to date. Though these patients are demographically unusual for DSRCT, including two women and two with rare extra-abdominal tumors of the brain and bone, through treatment of these patients we have accrued experience regarding various treatment strategies in both primary and refractory DSRCT. We treat primary DSRCT with interval-compressed vincristine/doxorubicin/cyclophosphamide alternating with cycles of ifosfamide/etoposide and irinotecan/temozolomide/temsirolimus (ITT). This is the first descriptive series of this size describing the use of ITT in DSRCT. Treatment for refractory cases focuses on targeted therapies when available, emphasizing the personalization that DSRCT treatment requires.

Biomarkers capable of predicting adverse melanoma patient responses to immune checkpoint inhibitor (ICI) therapies are an unmet need. Clinical biomarkers are largely prognostic and current response guidelines do not reflect the complex tumor-immune cell interaction dynamics attributed to ICI therapies. Validation of enhanced predictive biomarkers is dependent upon adoption of novel spatial imaging platforms capable of quantifying immune checkpoint receptor-ligand interactions within the tumor microenvironment. Assessments of these interactions at multiple points during neoadjuvant ICI regimens would inform biomarker selection based on changes in receptor-ligand interactions that best correlate with patient survival.

To compare an MRI-based radiomics signature with the programmed cell death ligand 1 (PD-L1) expression score for predicting immunotherapy response in nasopharyngeal carcinoma (NPC).

Consecutive patients with NPC who received immunotherapy between January 2019 and June 2022 were divided into training (n = 111) and validation (n = 66) sets. Tumor radiomics features were extracted from pretreatment MR images. PD-L1 combined positive score (CPS) was calculated using immunohistochemistry. The least absolute shrinkage and selection operator (LASSO) algorithm was used for feature selection and radiomics signature construction. Receiver operating characteristic (ROC) curve analysis was performed to assess prediction performance.

A total of eleven radiomics features with the greatest discrimination capability were identified by the LASSO algorithm to construct the radiomics signature. In predicting patients with objective response to immunotherapy, radiomics score (Rd-score) yielded a significantly higher area under the ROC curve than that of CPS in both the training (0.790 vs. 0.645, p = 0.025) and the validation (0.735 vs. 0.608, p = 0.038) sets. Multivariate analysis identified the Rd-score as an independent influencing factor in predicting immunotherapy response (odds ratio = 19.963, p < 0.001). Kaplan-Meier analysis indicated that patients with Rd-score ≥ 0.5 showed longer progression-free survival than patients with Rd-score < 0.5 (log-rank p < 0.01).

An MRI-based radiomics signature demonstrated greater efficacy than the PD-L1 expression score in predicting immunotherapy response in patients with NPC.

Question How does an MRI-based radiomics signature compare with the programmed cell death ligand 1 expression score for predicting immunotherapy response in nasopharyngeal carcinoma? Findings The MRI-based radiomics signature demonstrated superior predictive value compared with programmed cell death ligand 1 expression score in identifying immunotherapy responders. Clinical relevance MRI-based radiomics are a promising novel noninvasive tool for predicting immunotherapy outcomes in nasopharyngeal carcinoma.

We aimed to answer the following question: How effective is the addition of AKT inhibitors to the treatment of advanced or metastatic breast cancer?

We searched PubMed, Embase and Cochrane for randomized controlled trials (RCTs) that investigated AKT inhibitors for advanced or metastatic BC. We computed hazard-ratios (HRs) for binary endpoints.

A total of 5 RCTs were included in the meta-analysis, comprising 1,334 patients with BC. The use of AKT inhibitors demonstrated a significant improvement in OS (HR 0.70; 95% CI, 0.58-0.85; P < .001) and PFS (HR 0.6797; 95% CI, 0.5499-0.8403; P < .001) in the overall population. Within the PIK3CA/AKT1/PTEN-altered subgroup (n = 645), the OS rate also significantly favored AKT inhibitors over the control group (HR 0.62; 95% CI, 0.42-0.92; P = .019), as well as PFS (HR 0.5224; 95% CI, 0.3366-0.8105; P = .004).

Our findings suggest that the incorporation of AKT inhibitors holds promise for treating patients with advanced or metastatic PIK3CA/AKT1/PTEN-altered BC.

To provide up-to-date European Society of Urogenital Radiology (ESUR) guidelines for staging and follow-up of patients with ovarian cancer (OC).

Twenty-one experts, members of the female pelvis imaging ESUR subcommittee from 19 institutions, replied to 2 rounds of questionnaires regarding imaging techniques and structured reporting used for pre-treatment evaluation of OC patients. The results of the survey were presented to the other authors during the group's annual meeting. The lexicon was aligned with the Society of American Radiology (SAR)-ESUR lexicon; a first draft was circulated, and then comments and suggestions from the other authors were incorporated.

Evaluation of disease extent at diagnosis should be performed by chest, abdominal, and pelvic CT. The radiological report should map the disease with specific mention of sites that may preclude optimal cytoreductive surgery. For suspected recurrence, CT and [18F]FDG PET-CT are both valid options. MRI can be considered in experienced centres, as an alternative to CT, considering the high costs and the need for higher expertise in reporting.

CT is the imaging modality of choice for preoperative evaluation and follow-up in OC patients. A structured radiological report, including specific mention of sites that may preclude optimal debulking, is of value for patient management.

Question Guidelines were last published for ovarian cancer (OC) imaging in 2010; here, guidance on imaging techniques and reporting, incorporating advances in the field, are provided. Findings Structured reports should map out sites of disease, highlighting sites that limit cytoreduction. For suspected recurrence, CT and 18FDG PET-CT are options, and MRI can be considered. Clinical relevance Imaging evaluation of OC patients at initial diagnosis (mainly based on CT), using a structured report that considers surgical needs is valuable in treatment selection and planning.

GALOP investigators developed a multicenter protocol to standardize treatment for newly diagnosed metastatic Ewing sarcoma (ES) in South America.

Prospective trial. Induction chemotherapy consisted of 9 alternating interval-compressed cycles (every 14 days) of vincristine, doxorubicin, cyclophosphamide, and ifosfamide-etoposide; local and metastatic site control; and 5 consolidation cycles (every 21 days), followed by MCT with cyclophosphamide and vinblastine for 1 year.

Between 2011 and 2019, 198 patients were recruited from 34 centers in Argentina, Brazil, Chile, and Uruguay. Characteristics include: male patients (60.6%), median age of 12.3 years (range, 0.8-31.1); axial primary localization (62.1%), size >8 cm (70.2%); and bone origin (71.2%). Metastatic sites were lung, extra-lung, and combined in 43.4%, 31.3%, and 25.3%, respectively. The overall response rate was 79.3%, and local treatment was performed in 85.3% of patients. With a median follow-up of 65.1 months (95% CI: 53.9-76.4), the 5-year overall survival (OS) and event-free survival (EFS) were 33.1% (95% CI: 25.9-40.4) and 27.8% (95% CI: 21.5-34.3), respectively. The 5-year OS was 44.9%, 31.3%, and 15.6% for lung, extra-lung, and combined, respectively (p < 0.001). The median interval between induction chemotherapy cycles was 17 days, with a febrile neutropenia rate of 19.3%. Metronomic chemotherapy (MCT) was administered to 100 patients (50.5%), demonstrating good tolerability, with 58 patients completing at least 75% of the scheduled cycles.

The implementation of a multicenter protocol incorporating MCT for metastatic ES proved feasible across Latin America.

Large type 3 (≥ 8 cm) and type 4 gastric cancers (GCs) have poor prognoses and necessitate multidisciplinary treatment. A multi-institutional phase II study (OGSG1902) was conducted to assess the efficacy and safety of neoadjuvant chemotherapy (NAC) with docetaxel, oxaliplatin, and S-1 (DOS) in these patients.

Patients with large type 3 or type 4 GC without distant metastasis, except for positive peritoneal cytology (CY), were enrolled. Patients received three courses of neoadjuvant DOS therapy (docetaxel 40 mg/m2 and oxaliplatin 100 mg/m2 on day 1 via intravenous infusion, and S-1 80 mg/m2 orally for 14 days, repeated every 3 weeks) followed by gastrectomy. After R0 resection, adjuvant docetaxel/S-1 therapy was administered for 1 year.

From October 2019 to February 2022, 48 patients were enrolled. NAC was completed in 91.7% of patients. The R0 resection rate was 89.6%. The pathological response rate (Grade 1b-3) was 66.7%. Among patients with measurable lesions, the response rate was 50.0%. The CY-negative conversion rate was 80.0%, and the protocol completion rate was 45.8%. Grade 3 or 4 adverse events during NAC, including neutropenia and appetite loss, occurred in 37.5% of patients. Major postoperative complications (Clavien-Dindo Grade IIIa or higher) were observed in 2.1% of patients.

NAC with DOS for large type 3 or type 4 GC followed by gastrectomy demonstrated promising efficacy, high pathological response rates, and an acceptable toxicity profile. Further evaluation of long-term survival outcomes is ongoing.

To evaluate the role of multimodal magnetic resonance imaging radiomics features in predicting early recurrence of primary central nervous system lymphoma (PCNSL) and to investigate their correlation with patient prognosis.

A retrospective analysis was conducted on 145 patients with PCNSL who were treated with high-dose methotrexate-based chemotherapy. Clinical data and MRI images were collected, with tumor regions segmented using ITK-SNAP software. Radiomics features were extracted via Pyradiomics, and predictive models were developed using various machine learning algorithms. The predictive performance of these models was assessed using receiver operating characteristic (ROC) curves. Additionally, Cox regression analysis was employed to identify risk factors associated with progression-free survival (PFS).

In the cohort of 145 PCNSL patients (72 recurrence, 73 non-recurrence), clinical characteristics were comparable between groups except for multiple lesion frequency (61.1% vs. 39.7%, p < 0.05) and not receiving consolidation therapy (44.4% vs. 13.7%, p < 0.05). A total of 2392 radiomics features were extracted from CET1 and T2WI MRI sequence. Combining clinical variables, 10 features were retained after the feature selection process. The logistic regression (LR) model exhibited superior predictive performance in the test set to predict PCNSL early relapse, with an area under the curve (AUC) of 0.887 (95 % confidence interval: 0.785-0.988). Multivariate Cox regression identified the Cli-Rad score as an independent prognostic factor for PFS. Significant difference in PFS was observed between high- and low-risk groups defined by Cli-Rad score (8.24 months vs. 24.17 months, p < 0.001).

The LR model based on multimodal MRI radiomics and clinical features, can effectively predict early recurrence of PCNSL, while the Cli-Rad score could independently forecast PFS among PCNSL patients.

As described in ICH E3 Q&A R1 (International Council for Harmonisation. E3: Structure and content of clinical study reports-questions and answers (R1). 6 July 2012. Available from: https://database.ich.org/sites/default/files/E3_Q%26As_R1_Q%26As.pdf ): "A protocol deviation (PD) is any change, divergence, or departure from the study design or procedures defined in the protocol". A problematic area in human subject protection is the wide divergence among institutions, sponsors, investigators and IRBs regarding the definition of and the procedures for reviewing PDs. Despite industry initiatives like TransCelerate's holistic approach [Galuchie et al. in Ther Innov Regul Sci 55:733-742, 2021], systematic trending and identification of impactful PDs remains limited. Traditional Natural Language Processing (NLP) methods are often cumbersome to implement, requiring extensive feature engineering and model tuning. However, the rise of Large Language Models (LLMs) has revolutionised text classification, enabling more accurate, nuanced, and context-aware solutions [Nguyen P. Test classification in the age of LLMs. 2024. Available from: https://blog.redsift.com/author/phong/ ]. An automated classification solution that enables efficient, flexible, and targeted PD classification is currently lacking.

We developed a novel approach using a large language model (LLM), Meta Llama2 [Meta. Llama 2: Open source, free for research and commercial use. 2023. Available from: https://www.llama.com/llama2/ ] with a tailored prompt to classify free-text PDs from Roches' PD management system. The model outputs were analysed to identify trends and assess risks across clinical programs, supporting human decision-making. This method offers a generalisable framework for developing prompts and integrating data to address similar challenges in clinical development.

This approach flagged over 80% of PDs potentially affecting disease progression assessment, enabling expert review. Compared to months of manual analysis, this automated method produced actionable insights in minutes. The solution also highlighted gaps in first-line controls, supporting process improvement and better accuracy in disease progression handling during trials.

Docetaxel resistance, particularly post-androgen-receptor targeted therapy (ART), undermines its clinical utility in metastatic castration-resistant prostate cancer (mCRPC). This study explores the impact of docetaxel plus carboplatin (DC) chemotherapy on serum testosterone levels in metastatic docetaxel-resistant prostate cancer (mDRPC) patients. 123 mDRPC patients were categorized into three groups: (1) no previous ART (n = 65), (2) previous ART with serum free testosterone (FT) > detection limit (DL) at baseline (n = 31), and (3) previous ART with FT < DL at baseline (n = 27). Salvage DC chemotherapy led to significant reductions in FT and total testosterone (TT) levels in groups 1 and 2 (p < 0.05). Group 1 saw FT decrease from 0.85 pg/mL to below the DL (< 0.18 pg/mL) with 54.3% achieving complete reduction (CR); group 2 showed FT decrease from 0.28 pg/mL to below the DL with 67.7% achieving CR; group 3 had baseline FT values already below the DL with 96.3% maintaining this level. TT reductions to below the DL occurred in all groups. Low FT was an independent predictor for better PFS and for improved OS in groups 1 and 2. Our data indicate that adding carboplatin may improve the therapeutic effects of docetaxel in a castration-dependent setting.

This randomized phase-II trial (ClinicalTrials.gov identifier: NCT02767557) compared efficacy of gemcitabine/nab-paclitaxel (Gem/Nab) with or without the anti-interleukin-6 (IL-6) receptor antibody tocilizumab (Toc) for advanced pancreatic cancer (PC).

A safety cohort received Gem 1,000 mg/m2 and Nab 125 mg/m2 on days 1, 8, and 15, and Toc 8 mg/kg on day 1 for each 28-day cycle. Participants with modified Glasgow prognostic scores of 1 or 2 were randomly assigned 1:1 to receive Gem/Nab/Toc or Gem/Nab. The primary end point was the overall survival (OS) rate at 6 months (OS6). Secondary end points were progression-free survival (PFS), overall response rate (ORR), and safety. Exploratory end points were cachexia, quality of life, and biomarkers, including the cachexia-promoting protein, growth differentiation factor 15 (GDF15).

Overall, 147 patients were treated, including six safety cohort participants. The median follow-up period was 8.1 months (IQR, 4.2-13.9). OS6 was 68.6% (95% CI, 56.3 to 78.1) for the Gem/Nab/Toc group and 62.0% (49.6-72.1) for the Gem/Nab group (P = .409). OS for Gem/Nab/Toc versus Gem/Nab improved at 18 months (27.1% v 7.0%, P = .001). No differences in median OS, PFS, or ORR were observed. Incidence of grade-3+ treatment-related adverse events (TrAEs) was 88.1% for Gem/Nab/Toc and 63.4% for Gem/Nab (P < .001). Gem/Nab/Toc decreased muscle loss versus Gem/Nab, with median change +0.1013% versus -3.430% (P = .0012) at 2 months and +0.7044 versus -3.353% (P = .036) at 4 months. Incidence of muscle loss was 43.48% on Gem/Nab/Toc versus 73.52% on Gem/Nab at 2 months (P = .0045) and 41.82% versus 68.75% (P = .0062) at 4 months. GDF15 was not changed by Gem/Nab or Gem/Nab/Toc.

Although the primary end point was not met and TrAEs were increased by Toc, increased survival at 18 months and reduced muscle wasting support an anticachexia effect of IL-6 blockade independent of GDF15. Further studies could leverage these findings for precision anticachexia therapy.

Immune checkpoint inhibitors (ICIs) have dramatically transformed the therapeutic landscape of deficient mismatch repair/microsatellite unstable-high (dMMR/MSI-H) metastatic colorectal cancer (mCRC); however, ICI use is challenged by primary resistance and timing of discontinuation. Whether circulating tumor DNA (ctDNA) may be predictive of progression-free survival (PFS) and overall survival (OS) in this treatment context remains unknown.

To assess the prognostic and predictive role of ctDNA, detected by tumor-specific methylation markers, in patients with dMMR/MSI-H mCRC treated with ICIs.

This prespecified secondary analysis of the SAMCO-PRODIGE 54 randomized clinical trial evaluated ctDNA in patients with dMMR/MSI-H mCRC treated with avelumab or standard chemotherapy, with or without a targeted agent in the second-line setting, to assess its prognostic role. Plasma samples were obtained prospectively for ctDNA analysis, and digital droplet polymerase chain reaction amplification of bisulfite-converted cell-free DNA (cfDNA) for WIF1 and NPY genes was used to quantify ctDNA levels. These samples were collected from April 2018 to April 2021 at 49 sites in France at baseline (V1) and 1-month posttreatment initiation (V2) during. Data analyses were performed from October 1 to November 1, 2024.

Avelumab or standard chemotherapy with or without targeted agents.

PFS and OS according to baseline ctDNA positivity or concentration, and early ctDNA variation (ΔctDNA = [V1-V2] ÷ V1).

The predictive analysis included 99 patients (mean [SD] age, 66 [13] years; 51 female [51.5%]) with plasma samples available for ctDNA assessment at V1, of which 74 had samples available also at V2 for Change in ctDNA assessment. In the 99 patients with available V1 plasma samples, baseline ctDNA positivity or concentration were not associated with clinical outcomes. Change in ctDNA (cutoff at median value) was significantly associated with both PFS (hazard ratio [HR], 2.98; 95% CI, 1.77-5.01; P < .001) and OS (HR, 3.61; 95% CI, 1.81-7.17; P < .001). This association was evident in patients treated with avelumab (PFS HR, 4.22; 95% CI, 1.77-10.1; P = .001; OS HR, 17.40; 95% CI, 3.82-79.70; P < .001) than in those receiving chemotherapy (PFS HR, 2.09; 95% CI, 1.03-4.21; P = .04; OS HR, 1.51; 95% CI, 0.61-3.72; P = .38). Avelumab (vs chemotherapy) improved PFS in favorable ctDNA responders (HR, 0.33; 95% CI, 0.14-0.77; log-rank P = .008) but not in poor responders (HR, 1.32; 95% CI, 0.67-2.62; log-rank P = .42) Combined ctDNA response and RECIST, version 1.1, assessment accurately predicted long-term OS. In the multivariable analysis, lack of ctDNA response was associated with an increased risk of disease progression and death in the avelumab group (HR, 7.27; 95% CI, 2.23-23.7; P = .001) but not in the chemotherapy group (HR, 1.61; 95% CI, 0.66-3.93; P = .30).

The findings of this secondary analysis of an RCT found that change in ctDNA at 1-month posttreatment can predict long-term outcomes in patients with dMMR/MSI-H mCRC treated with ICIs.

ClinicalTrials.gov Identifier: NCT03186326.

Neoadjuvant immunotherapy has emerged as a promising strategy for treating esophageal squamous cell carcinoma (ESCC). This study evaluates the therapeutic efficacy and safety of neoadjuvant immunochemotherapy (nICT) in ESCC and explores potential biomarkers associated with treatment outcomes.

Patients with locally advanced ESCC were enrolled and received two cycles of nICT followed by surgical resection. The primary endpoint was the pathological complete response rate, while secondary endpoints included overall survival (OS), event-free survival (EFS), safety, and the identification of predictive biomarkers.

A total of 47 patients were enrolled in the study, with 42 undergoing surgical resection, all of whom achieved R0 resection. The rates of complete and partial pathological responses were 28.5% and 16.7%, respectively. The 1-year and 2-year EFS rates were 82% and 37.3%, while OS rates were 100% and 71.4%, respectively. The majority of treatment-related adverse events were Grade 1-2, and no surgical delays were observed. RNA sequencing analysis identified epithelial-mesenchymal transition as the most significantly enriched pathway in non-responders. Notably, higher infiltration of normal fibroblasts was associated with improved pathological response and enhanced long-term survival, while myofibroblastic cancer-associated fibroblasts (myCAF) negatively impacted treatment efficacy and clinical outcomes.

Neoadjuvant PD-1 inhibitors combined with chemotherapy show promising potential for patients with locally advanced ESCC, inducing a robust immune response that correlates with clinical outcomes. The infiltration of myCAF emerges as a potential predictive biomarker for treatment response and disease progression, underscoring the need for further mechanistic exploration and validation in larger cohorts.

Tyrosine kinase inhibitors (TKIs) have significantly improved the prognosis of patients with advanced medullary thyroid cancer (MTC). However, treatment response heterogeneity leads to challenges in predicting individual favourable response. This study evaluated the correlation between PET metrics on 68Ga-DOTATATE and 18F-FDG PET/CTs prior to treatment, and TKI response.

This study retrospectively evaluated patients with metastatic MTC who received TKIs at a tertiary care hospital and had prior 68Ga-DOTATATE and/or 18F-FDG PET/CT imaging. Patient demographics, treatment and PET/CT data were collected. Standardized Uptake Value (SUV) max, SUVmean, Total Lesion Activity (TLA) and Metabolic Tumor Volume (MTV) were determined per PET/CT.

In the 25 patients, mean age at diagnosis was 48 (±15) years; 11 (44%) were female and 21 tumors harbored RET driver alterations. Thirty-six TKI treatments were administered (11 patients received two TKIs sequentially). RECIST response rates (available in 32/36 treatments) included; stable disease in 8/32 (25%), partial response in 23/32 (72%) and complete response in 1/32 (3%) treatments. In total, 30 pre-TKI PET/CTs (24 68Ga-DOTATATE PET/CTs, 6 18F-FDG PET/CTs) were performed. Pre-TKI 68Ga-DOTATATE PET/CTs did not correlate with TKI treatment response. In the 18F-FDG cohort, high MTV and TLA correlated with a better structural response (p < 0.001) and high SUVmean correlated with a longer time to reach optimal response (p = 0.037).

In a small cohort of MTC patients, MTV and TLA on 18F-FDG PET/CT were associated with the structural response of TKI treatment, suggesting their potential utility in identifying patients who are likely to respond significantly. In contrast, TKI response showed no correlation with uptake on 68Ga-DOTATATE PET/CT.