Nivolumab plus ipilimumab with chemotherapy for non-small cell lung cancer with untreated brain metastases: A multicenter single-arm phase 2 trial (NIke, LOGiK 2004).

BACKGROUND: The effect of dual immunotherapy combined with platinum-based chemotherapy on untreated brain metastases derived from non-small cell lung cancer (NSCLC) has remained unclear. METHODS: This multicenter single-arm phase 2 study enrolled patients with chemotherapy-naïve advanced NSCLC and at least one brain metastasis ≥ 5 mm in size that had not been previously treated. Patients received nivolumab plus ipilimumab combined with platinum-doublet chemotherapy (two cycles), followed by nivolumab-ipilimumab alone. The primary endpoint of the study was intracranial response rate as determined by modified Response Evaluation Criteria in Solid Tumors (RECIST) for brain metastases of ≥ 5 mm as target lesions. RESULTS: A total of 30 patients from 18 institutions was enrolled in this study. The median age was 66.5 years (range, 47-83 years), and 26 patients (87 %) had a non-squamous cell carcinoma histology. The median size of all target brain lesions was 8.4 mm, with a range of 5-39 mm. The intracranial response rate assessed by modified RECIST was 50.0 % (95 % CI, 33.2-66.8 %), with the rate of complete response being 20.0 %, and the study met its primary endpoint. The systemic response rate was 53.3 % (95 % CI, 36.1-69.8 %), and responses for intracranial and extracranial lesions were generally consistent. The median intracranial progression-free survival was 8.1 months, and both the median intracranial duration of response and time to brain radiotherapy were not reached. CONCLUSION: Nivolumab plus ipilimumab combined with platinum-based chemotherapy showed promising intracranial activity in NSCLC patients with untreated brain metastases. TRIAL REGISTRATION: jRCT071210019.

A near-infrared fluorescent probe with assembly/aggregation-induced retention effect for specific diagnosis of metastasis and image-guided surgery in breast cancer.

Image-guided surgery is crucial for achieving complete tumor resection, reducing postoperative recurrence and improving patient survival. However, current clinical near-infrared fluorescent probes, such as indocyanine green (ICG), face two main limitations: 1) lack of active tumor targeting, and 2) short retention time in tumors, which restricts real-time imaging during surgery. To address these issues, we developed a near-infrared fluorescent probe capable of in situ nanofiber formation within tumor lesions. This probe actively targets the integrin αvß3 receptors overexpressed on breast cancer cells and exhibits assembly/aggregation-induced retention effects at the tumor site, significantly extending the imaging time window. Additionally, we found that the probe's fluorescence intensity can be enhanced under receptor induction. Due to its excellent tumor specificity and sensitivity, 1FCG-FFGRGD not only identifies primary breast cancer but also precisely locates smaller lymph node metastases and detects sub-millimeter peritoneal metastases. In summary, this near-infrared probe, leveraging assembly/aggregation-induced retention effects, holds substantial potential for various biomedical applications.

Preoperative stereotactic radiotherapy for the management of brain metastases.

Traditionally, postoperative whole-brain radiation therapy (WBRT) has been used for resected brain metastases, reducing local and intracerebral relapses. However, WBRT is associated with cognitive deterioration. Postoperative stereotactic radiotherapy (SRT) has emerged due to its neurocognitive preservation benefits. Despite its advantages, postoperative SRT has several drawbacks, including difficulties in target volume delineation, increased risk of radionecrosis (RN) and leptomeningeal disease (LMD), and prolonged treatment duration. Preoperative SRT has been proposed as a potential alternative, offering promising results in retrospective studies. Retrospective studies have suggested that preoperative SRT could achieve high local control rates with fewer LMD and RN rates compared to postoperative SRT. However, preoperative SRT is primarily based on retrospective data, and no phase 2/3 trials have been published to date. Ongoing clinical trials are expected to provide further insights into the efficacy and safety of preoperative SRT, addressing key questions regarding fractionation, dose, and timing relative to surgery.

Survival outcomes in patients with de novo metastatic Merkel cell carcinoma according to site of metastases.

Introduction: Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine malignancy of the skin with a predilection for metastases. This study investigates the clinical outcomes in patients presenting with de novo Stage IV MCC according to the metastatic site(s) at presentation. Materials and methods: Patients who presented with one or more sites of distant metastatic MCC at initial diagnosis between 2009 and 2023 were identified. The presence or absence of one or more metastases in each organ was categorized for each patient at the time of diagnosis. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Competing risk analysis was used to estimate the cumulative occurrence risk of MCC-specific death. Fisher's exact test was used for response rate analysis. Results were considered statically significant if p < 0.05. Results: Thirty-four patients presented with de novo distant metastatic MCC. There was no association between the number of metastatic sites at diagnosis and OS (p= 0.58), PFS (p=0.79), or response rates (p=0.53). However, the presence of bone metastases was associated with significantly shorter OS (8.2 versus 25.2 months, HR: 2.4, 95% CI 1.01-5.7, p= 0.04). MCC-specific death in patients with lymph node metastases was significantly lower than in patients without (HR: 0.28, 95% CI: 0.09-0.87, p= 0.013). The presence of bone metastases tended to associate with an increased risk of MCC-specific death, although not statistically significant. The location of metastases was not associated with the response rate to first-line treatment. There was no significant association between site of metastases and PFS. Conclusion: In this cohort of patients with de novo metastatic MCC, the presence of bone metastases, but not the number of organs involved, was associated with significantly worse OS. The presence of lymph node metastases was associated with lower MCC-specific death. Further research is warranted in larger cohorts to investigate the impact of the location of metastases on clinical outcomes.

Factors associated with the distribution of brain metastases in lung cancer: a retrospective study.

The distribution of brain metastases (BMs) in patients with lung cancer may be associated with the primary tumor-related factors and cerebral small vascular diseases (CSVDs). The aim of this study was to investigate the potential effects of the above factors on the distribution of BMs. A total of 5,788 lesions in 823 patients with BMs from lung cancer were enrolled. The numbers of BMs and CSVDs in 15 brain regions were determined. CSVDs include recent small subcortical infarcts (RSSIs), perivascular spaces, and lacunes of presumed vascular origin (LPVOs). We collected the number of CSVDs, and primary tumor-related factors (including clinical and imaging features) in lung cancer patients with BMs. Univariate and multivariate linear regression were utilized to analyze the potential influence of the above factors on the number of BMs in 15 brain regions. In addition, we performed subgroup analyses of all patients with adenocarcinoma (AD), female patients with AD, male patients with AD, and patients with small cell lung cancer. Univariate linear regression analyses showed that bone metastasis, adrenal metastasis, RSSIs, and LPVOs were associated with the number of BMs in over half of the examined brain regions. Only the independent association of LVPOs persisted in the multivariate linear regression analyses, and similar phenomenon was found in the subgroup analyses. In conclusion, the distribution of BMs in lung cancer patients appears to be associated with the presence of LVPOs, while primary tumor-related factors have less influence.

Return to work in younger patients with brain metastases who survived for 2 years or more.

PURPOSE: The study's purpose was to analyze return to work and other long-term outcomes in younger patients with newly diagnosed brain metastases, treated before they reached legal retirement age, i.e. younger than 65 years. METHODS: We included patients who survived greater than 2 years after their first treatment, regardless of approach (systemic therapy, neurosurgical resection, whole-brain or stereotactic radiotherapy). The primary endpoint was the proportion of patients who worked 2 years after their initial treatment for brain metastases. Outcomes beyond the 2-year cut-off were also abstracted from comprehensive electronic health records, throughout the follow-up period. RESULTS: Of 455 patients who received active therapy for brain metastases, 62 (14%) survived for > 2 years. Twenty-eight were younger than 65 years. The actuarial median survival was 81 months and the 5-year survival rate 53%. For patients alive after 5 years, the 10-year survival rate was 54%. At diagnosis, 25% of patients (7 of 28) were permanently incapacitated for work/retired. Of the remaining 21 patients, 33% did work 2 years later. However, several of these patients went on to receive disability pension afterwards. Eventually, 19% continued working in the longer run. Younger age, absence of extracranial metastases, presence of a single brain metastasis, and Karnofsky performance status 90-100 were common features of patients who worked after 2 years. CONCLUSION: Long-term survival was achieved after vastly different therapeutic approaches, regarding both upfront and sequential management. Many patients required three or more lines of brain-directed treatment. Few patients continued working in the longer run.

The combination of transarterial chemoembolization and microwave ablation is superior to microwave ablation alone for liver metastases from colorectal cancer.

OBJECTIVES: This study aimed to compare the combination therapy of transarterial chemoembolization (TACE) and microwave ablation (MWA) with MWA alone in treating liver metastases from colorectal cancer (LMCRC). MATERIALS AND METHODS: In this retrospective study, a total of 251 patients with unresectable and not to chemotherapy responding LMCRC were included. Group A consisted of 184 patients (104 male and 80 females; mean age: 64 ± 11.4 years) with 442 metastases who received a combination of TACE and MWA. A total of 67 patients (49 male and 18 females; mean age: 63.2 ± 11.8 years) with 173 metastases patients were included in group B, who received only MWA. Parameters assessed were local tumor progression (LTP), hepatic distant tumor progression (hDTP), hepatic progression-free survival (hPFS), and overall survival (OS). RESULTS: The rate of LTP was 4.9% in group A and 4.5% in group B (p-value: 0.062). The rate of hDTP was 71.7% and 83.6% for groups A and B (p-value: 0.81), respectively. The mean hPFS was 13.8 months (95% CI 10.9-16.8) for group A and 8.1 months (95% CI 6.1-10.1) for group B (p-value: 0.03). The median OS time for group A was 30 months (95% CI 26-34), with 1-, 2-, 3-, and 4-year OS rates of 84.2%, 61.1%, 40.8% and 31.3%, respectively. In group B however, the median OS time was 26 months (95% CI 18-34) with 1-, 2-, 3-, and 4-year OS rates of 82.3%, 53.2%, 34.6% and 28.2%, respectively (p-value: 0.67). CONCLUSION: The combination therapy of TACE and MWA is superior to the monotherapy of MWA for LMCRC, especially regarding hDTP, hPFS and OS.

Predicting the survival of patients with painful tumours treated with palliative radiotherapy: a secondary analysis using the 3-variable number-of-risk-factors model.

BACKGROUND: The 3-variable number-of-risk-factors (NRF) model is a prognostic tool for patients undergoing palliative radiotherapy (PRT). However, there is little research on the NRF model for patients with painful non-bone-metastasis tumours treated with PRT, and the efficacy of the NRF model in predicting survival is unclear to date. Therefore, we aimed to assess the prognostic accuracy of a 3-variable NRF model in patients undergoing PRT for bone and non- bone-metastasis tumours. METHODS: This was a secondary analysis of studies on PRT for bone-metastasis (BM) and PRT for miscellaneous painful tumours (MPTs), including non-BM tumours. Patients were grouped in the NRF model and survival was compared between groups. Discrimination was evaluated using a time-independent C-index and a time-dependent area under the receiver operating characteristic curve (AUROC). A calibration curve was used to assess the agreement between predicted and observed survival. RESULTS: We analysed 485 patients in the BM group and 302 patients in the MPT group. The median survival times in the BM group for groups I, II, and III were 35.1, 10.1, and 3.3 months, respectively (P < 0.001), while in the MPT group, they were 22.1, 9.5, and 4.6 months, respectively (P < 0.001). The C-index was 0.689 in the BM group and 0.625 in the MPT group. In the BM group, time-dependent AUROCs over 2 to 24 months ranged from 0.738 to 0.765, while in the MPT group, they ranged from 0.650 to 0.689, with both groups showing consistent accuracy over time. The calibration curve showed a reasonable agreement between the predicted and observed survival. CONCLUSIONS: The NRF model predicted survival moderately well in both the BM and MPT groups.

Radiofrequency ablation: mechanisms and clinical applications.

Radiofrequency ablation (RFA), a form of thermal ablation, employs localized heat to induce protein denaturation in tissue cells, resulting in cell death. It has emerged as a viable treatment option for patients who are ineligible for surgery in various diseases, particularly liver cancer and other tumor-related conditions. In addition to directly eliminating tumor cells, RFA also induces alterations in the infiltrating cells within the tumor microenvironment (TME), which can significantly impact treatment outcomes. Moreover, incomplete RFA (iRFA) may lead to tumor recurrence and metastasis. The current challenge is to enhance the efficacy of RFA by elucidating its underlying mechanisms. This review discusses the clinical applications of RFA in treating various diseases and the mechanisms that contribute to the survival and invasion of tumor cells following iRFA, including the roles of heat shock proteins, hypoxia, and autophagy. Additionally, we analyze| the changes occurring in infiltrating cells within the TME after iRFA. Finally, we provide a comprehensive summary of clinical trials involving RFA in conjunction with other treatment modalities in the field of cancer therapy, aiming to offer novel insights and references for improving the effectiveness of RFA.

Large Pleural Metastases With Significant Inter-fractional Volume Reduction During Online Adaptive Radiotherapy: A Case Report With Dosimetry Comparison.

Online adaptive radiotherapy (oART) dose calculation relies on synthetic computed tomography (sCT), which notably influences anatomical changes. This study elucidates how sCT may respond to significant inter-fractional tumor volume reduction and its subsequent impact on dose distribution. In this case report, we exported sCT and cone-beam CT (CBCT) images from each treatment session. We retrospectively analyzed 20 adaptive and scheduled plans of a patient receiving oART for large pleural metastases with notable inter-fractional tumor regression. By overriding the CT number of the dissipated tumor volume with that of the lungs on each sCT, we recalculated each plan. We compared the dose distribution between the adaptive and scheduled plans. Percentage dose difference and 3D gamma analysis were employed to assess dose variability. Results of the dose analysis showed that, compared to the online (non-overridden) plans, the recalculated plans using overridden sCT demonstrated right-shifted dose-volume histogram curves for the targets and right lung, with a slight but statistically significant increase of no less than 1.5% in D mean and D max for the targets and right lung. The location of hotspots shifted in alignment with tumor shrinkage and beam arrangement. Both recalculated adaptive and scheduled plans achieved ideal GTV, CTV, and PTV coverage, with adaptive plans significantly reducing the dose and irradiated volume to the right lung. In conclusion, as the pleural tumor volume decreased, online plans slightly underestimated the dose distribution and shifted the location of hotspots, though this remained clinically acceptable. Importantly, adaptive plans significantly minimized the irradiated volume of the critical OAR (right lung) while ensuring optimal dose coverage of the target volume, demonstrating the potential of sCT and adaptive oART to enhance treatment precision and efficacy in dynamically changing tumor environments.

Exophthalmos as the initial presentation of metastatic prostate cancer.

Primary metastatic prostate cancer to the orbit is exceedingly rare. Benign lesions, including meningioma, have demonstrated PSMA expression and can be visualized using PSMA-based PET tracers. We report the findings of 18F-PSMA-1007 PET/CT in a 76-year-old man with progressive confusion and long-standing blindness of the left eye. PET/CT scan revealed increased uptake of PSMA in the orbital and temporal region, and other sites throughout the body. Histopathological examination after biopsy of the left orbit showed adenocarcinoma of the prostate. This case substantiates the diverse clinical and radiological presentations of metastatic prostate cancer and underscores the diagnostic significance of targeted biopsy.

Spinal Diffuse Midline Glioma H3 K27M-Altered: Report of a Rare Tumor with Extracranial Skeletal Metastases and Review of Literature.

Diffuse midline glioma, H3 K27-altered is a rare and aggressive pediatric brain tumor with a grim prognosis. Diffuse midline glioma is characterized by specific molecular alterations, including H3 K27 mutations, and involves deep midline structures such as the brainstem, cerebellum, spinal cord, and thalamus. These tumors present with a classic triad of symptoms and have limited surgical options due to their challenging locations. Extra-neural metastases are an unusual occurrence in diffuse midline glioma and have been rarely described. Here we report a 17-year-old girl with spinal diffuse midline glioma, H3 K27M-mutant, who presented with multiple metastatic osseous lesions confirmed on biopsy of the thoracic vertebral lesion. Due to the rapid disease progression, the patient was recommended palliative therapy. Extra-neural metastases in diffuse midline glioma are rare, with only 16 reported patients, and no standard therapy exists. An accurate and early diagnosis is necessary to develop a personalized plan of treatment. Further research is needed to gain insights into the molecular pathology of diffuse midline glioma, H3 K27-altered, and improve the quality of life and the outcome of patients with this deadly disease.

New definition of borderline resectable colorectal liver metastasis based on prognostic outcomes.

BACKGROUND: Although surgical resection is the curative treatment for colorectal liver metastases (CRLM), the efficacy of neoadjuvant chemotherapy (NAC) has been discussed due to recent remarkable advances in chemotherapy. The definition of borderline resectable (BR) is most important, where neoadjuvant chemotherapy should be administered. This study aimed to examine a new definition of BR CRLM based on the results of the treatment outcomes. METHODS: This study included 127 patients who underwent liver resection for CRLM after exclusion of conversion cases between April 2010 and December 2023. Upfront resection was performed for synchronous and single liver metastasis or metachronous liver metastases. NAC was administered for multiple synchronous liver metastases. In order to find a new definition of BR, we examined the prognostic factors obtained from the treatment outcomes. RESULTS: CA19-9 level > 37.0 was the only prognostic factor in the upfront group [hazard ratio (HR) 2.386, 95% CI, 1.583-4.769; p = 0.049]. in the NAC group, a maximum tumor diameter ˃3 cm (HR 2.248, 95% CI 1.038-4,867, p = 0.040), CA19-9 level > 37.0 (HR 2.239, 95% CI 1.044-4.800, p = 0.038), and a right-sided primary tumor in the colon (HR 2.770, 95% CI 1.284-5.988, p = 0.009) were identified as significant prognostic factors. CONCLUSIONS: In cases of CRLM, patients with CA19-9 levels > 37.0, or CA19-9 level with < 37.0 but with a primary tumor in the right colon or a maximum tumor diameter of > 3 cm can be defined as BR CRLM and should be treated with NAC.

Evaluating Combinations of Biological and Clinicopathologic Factors Linked to Poor Outcomes in Resected Colorectal Liver Metastasis: An External Validation Study.

BACKGROUND: Recent studies have suggested that certain combinations of KRAS or BRAF biomarkers with clinical factors are associated with poor outcomes and may indicate that surgery could be "biologically" futile in otherwise technically resectable colorectal liver metastasis (CRLM). However, these combinations have yet to be validated through external studies. PATIENTS AND METHODS: We conducted a systematic search to identify these studies. The overall survival (OS) of patients with these combinations was evaluated in a cohort of patients treated at 11 tertiary centers. Additionally, the study investigated whether using high-risk KRAS point mutations in these combinations could be associated with particularly poor outcomes. RESULTS: The recommendations of four studies were validated in 1661 patients. The first three studies utilized KRAS, and their validation showed the following median and 5-year OS: (1) 30 months and 16.9%, (2) 24.3 months and 21.6%, and (3) 46.8 months and 44.4%, respectively. When analyzing only patients with high-risk KRAS mutations, median and 5-year OS decreased to: (1) 26.2 months and 0%, (2) 22.3 months and 15.1%, and (3) not reached and 44.9%, respectively. The fourth study utilized BRAF, and its validation showed a median OS of 10.4 months, with no survivors beyond 21 months. CONCLUSION: The combinations of biomarkers and clinical factors proposed to render surgery for CRLM futile, as presented in studies 1 (KRAS high-risk mutations) and 4, appear justified. In these studies, there were no long-term survivors, and survival was similar to that of historic cohorts with similar mutational profiles that received systemic therapies alone for unresectable disease.

Intracranial outcomes following neurosurgical resection in patients with brain metastases secondary to HER2-positive breast cancer versus other subtypes.

PURPOSE: Neurosurgical resection serves an important role in select patients with breast cancer and brain metastases but can delay systemic therapy and yield complications. Consequently, identification of patients most likely to benefit from surgery is important. Given the poorer long-term intracranial responses to radiotherapy sometimes observed in HER2-positive (HER2 +) patients, we investigated whether neurosurgical resection is differentially beneficial in this population. METHODS: We identified 633 patients with newly diagnosed brain metastases arising from breast cancer managed at Brigham and Women's Hospital/Dana-Farber Cancer Institute between 2010 and 2022. Patients were stratified by breast cancer subtype: HER2 + (N = 189), hormone receptor positive (HR +)/HER2- (N = 267), and triple negative (N = 177). Per-patient and per-metastasis outcomes were evaluated; interaction models assessing the impact of neurosurgical resection by subtype were constructed. RESULTS: Relative to HR + /HER2- subtype, omission of upfront neurosurgical resection in patients with HER2 + disease was associated with increased subsequent utilization of salvage stereotactic radiation, whole brain radiotherapy, and craniotomy (interaction HR 2.02 [95% CI, 1.04-3.93], p = 0.04; HR 3.92 [95% CI, 1.24-12.40], p = 0.02; HR 4.98 [95% CI, 1.34-18.58], p = 0.02, respectively). Tumors stemming from HER2 + versus HR + /HER2- primaries displayed increased local recurrence when upfront neurosurgical resection was omitted (interaction HR 3.62 [95% CI, 1.06-12.38], p = 0.04). No such associations were noted when comparing triple negative to HR + /HER2- subtype (p-interaction > 0.05 in all cases). CONCLUSION: Patients with HER2 + disease and brain metastases may disproportionately benefit from upfront neurosurgical resection relative to other subtypes. If validated, our results may suggest a lower threshold to consider surgery in brain metastases secondary to HER2 + breast cancer.

RTOG 0915-compliant patient specific QA for lung stereotactic body radiotherapy using the new PTW 1600SRS detector array.

PURPOSE: An area of focus in radiotherapy is the treatment of oligometastatic lung cancer using highly conformal techniques such as SBRT, performed using VMAT that involves flattening filter free (FFF) beams. This study proposes a new calibration procedure for PTW Octavius 1600SRS detector array and was designed to also evaluate clinical and dosimetric aspects of a patient-specific quality assurance (PSQA) for lung SBRT patients. METHODS: The cohort consists of 20 patients, treated for lung metastases using SBRT with 50 Gy dose in 5 fractions (10 Gy/fr). The proposed calibration method uses only one calibration factor determined at maximum dose rate of 6MV FFF photon beam. The dosimetric accuracy of achieving a high dose gradient was analyzed using the RTOG 0915 protocol and was confirmed by PSQA procedures using the PTW Octavius 1600SRS detector. RESULTS: Conformity index, gradient index, maximum dose at 2 cm and V20 parameters were evaluated with clinical favorable results, with only two plans with lesions situated in the inferior lobe exceeding the deviation allowed for the gradient index. Gamma passing rates using the new calibration method were 98.93% and 99.38% for different gamma criteria of 2 mm/2% and 1 mm/3%, respectively. CONCLUSIONS: The proposed method for calibration using one calibration factor at maximum dose rate for the involved photon beam shows clinically acceptable gamma passing rates. Employing the RTOG 0915 protocol for lung SBRT treatment plan evaluation brings important dosimetric information about treatment plan quality and dose gradient fall-off which can be correlated with the results achieved during the pretreatment verification procedures.

T lymphocyte recruitment to melanoma brain tumors depends on distinct venous vessels.

To improve immunotherapy for brain tumors, it is important to determine the principal intracranial site of T cell recruitment from the bloodstream and their intracranial route to brain tumors. Using intravital microscopy in mouse models of intracranial melanoma, we discovered that circulating T cells preferably adhered and extravasated at a distinct type of venous blood vessel in the tumor vicinity, peritumoral venous vessels (PVVs). Other vascular structures were excluded as alternative T cell routes to intracranial melanomas. Anti-PD-1/CTLA-4 immune checkpoint inhibitors increased intracranial T cell motility, facilitating migration from PVVs to the tumor and subsequently inhibiting intracranial tumor growth. The endothelial adhesion molecule ICAM-1 was particularly expressed on PVVs, and, in samples of human brain metastases, ICAM-1 positivity of PVV-like vessels correlated with intratumoral T cell infiltration. These findings uncover a distinct mechanism by which the immune system can access and control brain tumors and potentially influence other brain pathologies.

KL-6 Mucin as Serum Tumor Marker of Metastatic Renal Cancer: A Case Report.

We encountered a case of metastatic renal cell carcinoma in which the serum level of KL-6, a therapeutic marker, was exceptionally high and fluctuated with the progression of treatment. A 74-year-old man was diagnosed with right renal cystic cancer and multiple metastases in October 2022. The KL-6 level was 27490 U/mL. He started treatment with lenvatinib and pembrolizumab. KL-6 decreased to 3885 U/mg in February 2023. The patient's proteinuria worsened, leading to the discontinuation of lenvatinib. KL-6 increased to 25950 U/mL in April. He discontinued pembrolizumab and started taking cabozantinib. In September, drug-induced bilateral inflammatory pneumonitis developed. He discontinued cabozantinb and began taking axitinib. KL-6 decreased; however, he suffered from severe diarrhea and subsequent renal insufficiency. He discontinued axitinib in November. KL-6 increased to 29640 U/mL in December.

A simple sore can lead to limb amputation; metastatic squamous cell carcinoma of the sole in a 22-year-old man.

INTRODUCTION AND IMPORTANCE: Squamous cell carcinoma (SCC) is a cancerous tumor that can develop when normal keratinocytes undergo a transformation into invasive cancer cells, typically due to genetic mutations that affect cell growth and differentiation. SCC is frequently found on sun-exposed areas of the skin like the face, ears, neck, and hands, but it is unusual to see it develop on the soles of the feet. CASE REPORT: This case is about a 22-year-old man who came in with a persistent sore on the bottom of his left foot. The patient mentioned sustaining a small injury to his foot about two weeks before seeking medical help, which started off as a minor wound but deteriorated over time. Ultimately, the diagnosis revealed squamous cell carcinoma that had spread to the lungs and lymph nodes. DISCUSSION: This case highlights the importance of considering the possibility of malignancy in non-healing wounds, even in young patients without known risk factors. The initial presentation of a simple sore that progressed to metastatic SCC underscores the challenges in diagnosing and managing skin cancers in atypical presentations. CONCLUSION: This case highlights cancer's aggressiveness and atypical youth presentations, stressing early detection, aggressive treatment, and comprehensive patient support. Continued research is crucial for enhancing disease management.

Computed Tomography-Based Radiomics with Machine Learning Outperforms Radiologist Assessment in Estimating Colorectal Liver Metastases Pathologic Response After Chemotherapy.

OBJECTIVES: This study was designed to assess computed tomography (CT)-based radiomics of colorectal liver metastases (CRLM), extracted from posttreatment scans in estimating pathologic treatment response to neoadjuvant therapy, and to compare treatment response estimates between CT-based radiomics and radiological response assessment by using RECIST 1.1 and CT morphologic criteria. METHODS: Patients who underwent resection for CRLM from January 2003-December 2012 at a single institution were included. Patients who did not receive preoperative systemic chemotherapy, or without adequate imaging, were excluded. Imaging characteristics were evaluated based on RECIST 1.1 and CT morphologic criteria. A machine-learning model was designed with radiomic features extracted from manually segmented posttreatment CT tumoral and peritumoral regions to identify pathologic responders (≥ 50% response) versus nonresponders. Statistical analysis was performed at the tumor level. RESULTS: Eighty-five patients (median age, 62 years; 55 women) with 95 tumors were included. None of the subjectively evaluated imaging characteristics were associated with pathologic response (p > 0.05). Inter-reader agreement was substantial for RECIST categorical response assessment (K = 0.70) and moderate for CT morphological group response (K = 0.50). In the validation cohort, the machine learning model built with radiomic features obtained an area under the curve (AUC) of 0.87 and outperformed subjective RECIST assessment (AUC = 0.53, p = 0.01) and morphologic assessment (AUC = 0.56, p = 0.02). CONCLUSIONS: Radiologist assessment of oligometastatic CRLM after neoadjuvant therapy using RECIST 1.1 and CT morphologic criteria was not associated with pathologic response. In contrast, a machine-learning model based on radiomic features extracted from tumoral and peritumoral regions had high diagnostic performance in assessing responders versus nonresponders.