The role of multimodality imaging in the selection and management of patients treated with cytoreductive surgery and HIPEC.

Cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC) is the mainstay of potentially curative surgical treatment for malignancies that have spread to peritoneal surfaces. This surgical procedure is however associated with high morbidity and appropriate patient selection and planning is therefore essential. Available multimodality imaging techniques include CT with oral and intravenous contrast, MRI including use of dedicated peritoneal protocol and FDG-PET/CT. These used with the correct technique, read by specialist radiologists and discussed under the auspices of a dedicated multidisciplinary team, can help to improve outcomes. We demonstrate that imaging not only provides information about peritoneal disease burden but more importantly want to shift the reader's focus to disease distribution. Our examples highlight how imaging helps avoid futile surgery by identifying patients with disease in unfavourable sites and show the strength and limitations of the various imaging modalities. We share how MR imaging can help identify multifocal and often occult sites including widespread miliary disease. Our examples provide a comprehensive overview demonstrating how imaging can help plan surgery by identifying patients who may need splenic vaccinations, counselling for stoma, egg harvesting and input from surgeons with other specialist expertise greatly increasing likelihood of achieving complete cytoreduction.

CT and MRI Findings of Renal Angiomyolipoma With Lung Metastasis: A Case Report and Literature Review.

Renal angiomyolipoma has two histological variants: classical and epithelioid. Epithelioid angiomyolipoma is considered as a potential malignant tumor, often leading to recurrence and metastasis, with rapid progression in most of the cases. The lung is one of the most commonly reported sites of metastasis, and pulmonary metastasis of renal angiomyolipoma is usually diagnostic by computed tomography (CT) scans. Here, we report for the first time renal angiomyolipoma with lung metastasis by combining CT and magnetic resonance imaging (MRI).

Implications of bone metastasis on response to systemic therapy in patients with advanced renal cell carcinoma: A systematic literature review.

INTRODUCTION: Bone metastases negatively affect prognosis in patients with advanced renal cell carcinoma (aRCC). We conducted a systematic literature review to identify clinical trial publications including patients with aRCC with and without bone metastases. METHODS: The review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta­Analyses (PRISMA) guidelines and registered with PROSPERO (CRD42022355436). MEDLINE and Embase databases were searched (September 2, 2022) to identify publications reporting efficacy and safety outcomes for patients with/without bone metastasis from clinical trials of systemic RCC therapies. Risk of bias was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: Of 526 publications screened, 19 were eligible: seven (from five studies) reported phase 3 trials, six reported phase 2 trials, one reported phase 1b/2 trials, and five were pooled analyses. Five publications reported moderate-quality evidence, while 14 were graded as low- or very low-quality evidence, suggesting a high potential for uncertainty. Five studies reported benefits of investigational therapies versus comparators in patients with and without bone metastases; these studies included cabozantinib, nivolumab, cabozantinib plus nivolumab, and lenvatinib plus pembrolizumab treatment arms. Data were also available for nivolumab plus ipilimumab. Bone metastases were consistently associated with poor prognosis in patients with aRCC. Preliminary data support the hypothesis that therapies targeting pathways implicated in the development of bone metastases may be beneficial, and warrant further investigation. However, data to support treatment decision-making are lacking. CONCLUSION: Our findings highlight the need for clinical data to assist in defining the optimal treatment for patients with aRCC and bone metastasis.

Prognostic value of lateral lymph node metastasis in pretreatment MRI for rectal cancer in patients undergoing neoadjuvant chemoradiation followed by surgical resection without lateral lymph node dissection: A systemic review and meta-analysis.

PURPOSE: To systematically review and meta-analyze the prognostic significance of lateral lymph node metastasis (LLNM) on pretreatment MRI in patients with rectal cancer who undergo neoadjuvant chemoradiation followed by curative surgical resection without lateral lymph node dissection (LLND). METHODS: We searched the MEDLINE and EMBASE databases until September 27, 2023, utilizing the following search terms: (rectal OR rectum OR colorectal) AND (lateral OR sidewall) AND (lymph OR node). The QUIPS tool was employed to evaluate methodological quality. We pooled the association between LLNM on pretreatment MRI and outcomes such as local recurrence, distant metastasis, disease-free survival, and overall survival using hazard ratio (HR) and odds ratio (OR) based on random effects model. RESULTS: We included 9 studies, encompassing 3180 patients. LLNM on pretreatment MRI revealed a significant association with increased local recurrence rates (HR: 4.11; 95 % CI: [1.87, 9.02]) and elevated risks for both disease-free (HR: 1.70; 95 % CI: [1.42, 2.03]) and overall survival (HR: 1.76; 95 % CI: [1.44, 2.15]). As for distant metastasis, our analysis indicated a potential trend towards increased rates, though this did not reach statistical significance (HR: 1.67; 95 % CI: [0.85, 3.27]). CONCLUSIONS: Our findings underscore the relationship between LLNM and increased local recurrence and compromised disease-free and overall survival. This emphasizes the potential limitations of relying solely on neoadjuvant chemoradiation and highlights the potential need to intensify treatment in select patients.

Trends in incidence of infrequent and frequent synchronous metastases from colorectal cancer.

BACKGROUND: Population-based data on the incidence of frequent colorectal metastases are fairly scarce, while that on rare metastatic sites are lacking. AIMS: The aim of this study was to provide epidemiological indicators of metastatic sites frequency in patients with colorectal cancer. METHODS: Incidence was modelled using Poisson and Joinpoint regressions in a population-based cancer registry study including metastatic colorectal cancers diagnosed between 1991 and 2020 (N = 5,199). Tumor molecular markers were collected for the [2016-2020] period. RESULTS: Liver, peritoneum, lung and bone were the most frequent metastatic sites. Among frequent sites, incidence of liver and lung sites decreased in men respectively since 1999 and 2010, whereas in women incidence of liver and peritoneum sites increased steadily throughout the whole period. Each of the other sites concerned less than 3% of metastatic colorectal cancer cases and presented standardized incidence rates between 0.19 and 1.39 per 1,000,000. Among rare sites, incidence of adrenal glands, supraclavicular lymph node, mediastinum and ascites had doubled in [2016-2020] as compared to the 25 previous years. BRAFV600E variant was more frequent in presence of carcinomatosis, and absence of liver and lung metastasis while KRAS variant was more frequent in presence of lung metastasis. CONCLUSION: This study provides unprecedented incidence indicators for rare synchronous metastases of colorectal cancer.

Case report: Drug-eluting bead transcatheter arterial chemoembolization in liver metastasis and retroperitoneal lymph node metastases of renal cell carcinoma: effective local therapy with the first report.

The liver is the fourth most common site of metastasis in renal cell carcinoma (RCC), which is usually treated with systemic therapies and local treatments. However, local treatments are challenging in RCC patients with liver metastasis who failed in first-line systemic therapy. Here, we report a case of a patient with both liver-dominant RCC metastasis and recurrence in the operative site who had failed in first-line targeted therapy plus immunotherapy, received drug-eluting bead transcatheter arterial chemoembolization (DEB-TACE), and achieved a complete response.

Presentation of metastatic carotid body paraganglioma on F-18 FDG PET/CT: a rare disease.

Carotid body paraganglioma is a slow growing tumor of head and neck region. It can rarely be malignant in nature which is characterized by distant metastases on anatomical imaging. We share an interesting presentation of a malignant carotid body on F-18 FDG PET/CT in form of liver and skeletal metastases.

Surgery for Infrarenal Retroperitoneal Node Metastases from Colon Cancer.

PURPOSE: Treatment of retroperitoneal lymph node metastases (RPN) from colon cancer (CC) is a therapeutic challenge. Available evidence supporting a curative approach is weak and uncertainties remain concerning the extent of the dissection, the optimal timing for surgery, and the role of adjuvant radiotherapy. We report the outcomes of a curative intent strategy in a recent monocentric series of patients. METHODS: We did a retrospective review of all curative intent surgical treatment of RPN from CC performed consecutively in a French university hospital from June 2015 to April 2021. Demographics, clinicopathological, and molecular characteristics were evaluated. We describe recurrence-free and overall survival and factors related to recurrence. RESULTS: Records from 18 patients were reviewed. The median age was 69 years. Most of the patients were male (55%), ASA 1-2 (94%), had a left-sided primary colon cancer (73%), and had metachronous RPN (62%). Thirteen patients (72%) experienced recurrence. Recurrence was often limited to RPN (27%) or liver (22%). Four patients underwent a second surgery for RPN recurrence. Median disease-free and overall survival were 22 months and 50 months after RPN surgery. We did not find any factor associated with recurrence. Short-term recurrence (< 6 months) was associated with shorter overall survival (0.031). CONCLUSION: The current results suggest that RPN resection is feasible and associated with long survival in selected patients. Further studies evaluating the benefit of curative strategies including radical surgery for patients with potentially resectable RPN are warranted.

Spotlight on the treatment of non-small cell lung cancer with rare genetic alterations and brain metastasis: Current status and future perspectives.

In patients with non-small cell lung cancer (NSCLC), oncogenic variants present in <5% of cases are considered rare, the predominant of which include human epidermal growth factor receptor 2 (HER2) mutations, mesenchymal-epithelial transition (MET) alterations, c-ros oncogene 1 (ROS1) rearrangements, rearrangement during transfection (RET) fusions, v-raf mouse sarcoma virus oncogene homolog B1 (BRAF) mutations, and neurotrophic troponin receptor kinase (NTRK) fusions. Brain metastases (BMs) occur in approximately 10%-50% of patients with NSCLC harboring rare genetic variants. The recent advent of small-molecule tyrosine kinase inhibitors and macromolecular antibody-drug conjugates (ADCs) has conferred marked survival benefits to patients with NSCLC harboring rare driver alterations. Despite effective brain lesion control for most targeted agents and promising reports of intracranial remission associated with novel ADCs, BM continues to be a major therapeutic challenge. This review discusses the recent advances in the treatment of NSCLC with rare genetic variants and BM, with a particular focus on intracranial efficacy, and explores future perspectives on how best to treat these patients.

Spinal extradural meningioma: Report of two cases.

Purely extradural spinal meningiomas are rare and often confused with metastases and schwannomas. Only a few cases have been described in the literature, and they are located mainly in the cervical and dorsal regions. We present two cases of extradural meningiomas, one well-defined nodular growth present at a cervicodorsal junction that was confused with schwannoma preoperatively and the other typical meningioma extending both intra and extradurally in the upper dorsal spine.

Assessing survival in non-small cell lung cancer brain metastases after stereotactic radiosurgery: before and after the start of the targetable mutation era.

PURPOSE: Targeted treatment options for non-small cell lung cancer (NSCLC) brain metastases (BMs) may be combined with stereotactic radiosurgery (SRS) to optimize survival. We assessed patient outcomes after SRS for NSCLC BMs, identifying survival trajectories associated with targetable mutations. METHODS: In this retrospective time-dependent analysis, we analyzed median overall survival of patients who received ≥ 1 SRS courses for BM from NSCLC from 2001 to 2021. We compared survival of patients with and without targetable mutations based on clinical variables and treatment. RESULTS: Among the 213 patients included, 87 (40.8%) had targetable mutations-primarily EGFR (22.5%)-and 126 (59.2%) did not. Patients with targetable mutations were more often female (63.2%, p <.001) and nonsmokers (58.6%, p <.001); had higher initial lung-molGPA (2.0 vs. 1.5, p <.001) and lower cumulative tumor volume (3.7 vs. 10.6 cm3, p <.001); and received more concurrent (55.2% vs. 36.5%, p =.007) and total (median 3 vs. 2, p <.001) systemic therapies. These patients had lower mortality rates (74.7% vs. 91.3%, p <.001) and risk (HR 0.298 [95%CI 0.190-0.469], p <.001) and longer median overall survival (20.2 vs. 7.4 months, p <.001), including survival ≥ 3 years (p =.001). Survival was best predicted by SRS with tumor resection in patients with non-targetable mutations (HR 0.491 [95%CI 0.318-757], p =.001) and by systemic therapy with SRS for those with targetable mutations (HR 0.124 [95%CI 0.013-1.153], p =.067). CONCLUSION: The presence of targetable mutations enhances survival in patients receiving SRS for NSCLC BM, particularly when used with systemic therapies. Survival for patients without targetable mutations was longest with SRS and surgical resection. These results inform best practices for managing patients with NSCLC BM based on driver mutation status.

Accumulation of liposomes in metastatic tumor sites is not necessary for anti-cancer drug efficacy.

BACKGROUND: The tumor microenvironment is profoundly heterogeneous particularly when comparing sites of metastases. Establishing the extent of this heterogeneity may provide guidance on how best to design lipid-based drug delivery systems to treat metastatic disease. Building on our previous research, the current study employs a murine model of metastatic cancer to explore the distribution of ~ 100 nm liposomes. METHODS: Female NCr nude mice were inoculated with a fluorescently labeled, Her2/neu-positive, trastuzumab-resistant breast cancer cell line, JIMT-1mkate, either in the mammary fat pad to create an orthotopic tumor (OT), or via intracardiac injection (IC) to establish tumors throughout the body. Animals were dosed with fluorescent and radio-labeled liposomes. In vivo and ex vivo fluorescent imaging was used to track liposome distribution over a period of 48 h. Liposome distribution in orthotopic tumors was compared to sites of tumor growth that arose following IC injection. RESULTS: A significant amount of inter-vessel heterogeneity for DiR distribution was observed, with most tumor blood vessels showing little to no presence of the DiR-labelled liposomes. Further, there was limited extravascular distribution of DiR liposomes in the perivascular regions around DiR-positive vessels. While all OT tumors contained at least some DiR-positive vessels, many metastases had very little or none. Despite the apparent limited distribution of liposomes within metastases, two liposomal drug formulations, Irinophore C and Doxil, showed similar efficacy for both the OT and IC JIMT-1mkate models. CONCLUSION: These findings suggest that liposomal formulations achieve therapeutic benefits through mechanisms that extend beyond the enhanced permeability and retention effect.

68Ga-PSMA-11 PET and mpMRI in the diagnosis of initial lymph node staging of prostate cancer: a head-to-head comparative meta-analysis.

Purpose: This meta-analysis evaluates the comparative diagnostic efficacy of 68Ga-prostate-specific membrane antigen-11 PET (68Ga-PSMA-11 PET) and multiparametric MRI (mpMRI) for the initial lymph node staging of prostate cancer. Methods: We searched PubMed and Embase databases through October 2023 for studies that provide a head-to-head comparison of 68Ga-PSMA-11 PET and mpMRI, using pelvic lymph node dissection as the gold standard. We assessed sensitivity and specificity using the DerSimonian and Laird method, with variance stabilization via the Freeman-Tukey double inverse sine transformation. The quality of included studies was evaluated using the Quality Assessment of Diagnostic Performance Studies (QUADAS-2) tool. Results: The meta-analysis incorporated 13 articles, involving a total of 1,527 patients. 68Ga-PSMA-11 PET demonstrated an overall sensitivity of 0.73 (95% CI: 0.51-0.91) and a specificity of 0.94 (95% CI: 0.88-0.99). In comparison, mpMRI showed a sensitivity of 0.49 (95% CI: 0.30-0.68) and a specificity of 0.94 (95% CI: 0.88-0.99). Although 68Ga-PSMA-11 PET appeared to be more sensitive than mpMRI, the differences in sensitivity (p = 0.11) and specificity (p = 0.47) were not statistically significant. Conclusion: Our findings indicated that 68Ga-PSMA-11 PET and mpMRI exhibit similar sensitivity and specificity in the diagnosis of initial lymph node staging of prostate cancer. However, given that most included studies were retrospective, further prospective studies with larger sample sizes are essential to validate these results. Systematic Review Registration: PROSPERO code is CRD42023495266.

FINAL outcome ANALYSIS FROM THE PHASE II TUXEDO-1 TRIAL OF TRASTUZUMAB-DERUXTECAN IN HER2-positive breast cancer PATIENTS WITH active brain metastases.

BACKGROUND: Brain metastases (BM) are a devastating complication of HER2-positive metastatic breast cancer (BC) and treatment strategies providing optimized local and systemic disease control are urgently required. The antibody-drug conjugate (ADC) trastuzumab deruxtecan (T-DXd) improved progression-free survival (PFS) and overall survival (OS) over trastuzumab emtansine but data regarding intracranial activity is limited. In the primary outcome analysis of TUXEDO-1, a high intracranial response rate (RR) was reported with T-DXd. Here, we report final PFS and OS results. PATIENTS AND METHODS: TUXEDO-1 accrued adult patients with HER2-positive BC and active BM (newly diagnosed or progressing) without indication for immediate local therapy. The primary endpoint was intracranial RR; secondary endpoints included PFS, OS, safety, quality-of-life (QoL), and neurocognitive function. PFS and OS were estimated with the Kaplan-Meier method and analysed in the per-protocol population. RESULTS: At 26.5 months median follow-up, median PFS was 21 months (95% CI 13.3-n.r.) and median OS was not reached (95% CI 22.2-n.r.). With longer follow-up, no new safety signals were observed. The most common grade 3 adverse event was fatigue (20%). Grade 2 interstitial lung disease and a grade 3 symptomatic drop of left-ventricular ejection fraction were observed in one patient each. QoL was maintained over the treatment period. DISCUSSION: T-DXd yielded prolonged intra- and extracranial disease control in patients with active HER2-positive BC BM in line with results from the pivotal trials. These results support the concept of ADCs as systemic therapy for active BM.

Metastatic Pleomorphic Carcinoma of the Lung with Extensive Chromosomal Rearrangements: An Autopsy Case with a Literature Review.

We herein report a 47-year-old man who presented with progressive paraparesis. Imaging revealed a right upper pulmonary nodule, massive bilateral adrenal metastases, thoracolumbar vertebral osteolysis, and subcutaneous nodules. A biopsy of the right buttock nodule revealed a poorly differentiated metastatic carcinoma with high programmed cell death-ligand 1 expression and extensive chromosomal rearrangements. The patient died 10 days after the initiation of pembrolizumab treatment. Autopsy findings confirmed pulmonary pleomorphic carcinoma with extensive metastases. Quantification of chromosomal rearrangements revealed a jump-up mutation from the normal karyotype, followed by a further incremental increase in the degree of deviation.

Patterns of brain metastases response to immunotherapy with pembrolizumab.

PURPOSE: Central nervous system (CNS) metastases from lung cancers and melanoma, significantly contribute to morbidity and mortality. Despite advances in local therapies, there is a need for effective systemic treatments. Pembrolizumab, a PD-1 inhibitor, has shown promise for some patients with untreated brain metastases from melanoma and non-small cell lung cancer (NSCLC). This study aims to analyze the response of brain metastasis to pembrolizumab and associate characteristics like size and location with treatment outcome. METHODS: This retrospective study used imaging data from a phase II trial of pembrolizumab in melanoma or NSCLC patients with untreated brain metastases. MRI evaluations were conducted at 2 month intervals, with each brain metastasis treated as a distinct tumor for response assessment, based on modified RECIST criteria (maximum 5 lesions, 5 mm target lesions). RESULTS: Of 130 individual target metastases (> 5 mm), in 65 patients with NSCLC (90 metastases) and Melanoma (40 metastases), 32 (24.6%) demonstrated complete resolution, 24 (18.5%) had partial resolution, 32 (24.6%) were SD and 42 (32.3%) demonstrated PD. Those smaller than 10 mm were more likely to show complete resolution (p = 0.0218), while those ≥ 10 mm were more likely to have PR. There was no significant association between size, number or location (supratentorial vs. infratentorial) and lesion progression. The median time to metastatic lesion progression in the brain was 5.7-7 weeks. CONCLUSION: Pembrolizumab is effective in brain metastases from NSCLC and melanoma, showing response (CR + PR) in 43% and progression (PD) in 32% of metastases. With the median time to CNS progression of 5.7-7 weeks, careful radiographic monitoring is essential to guide timely local treatment decisions.

6,126 hepatectomies in 2022: current trend of outcome in Italy.

PURPOSE: Whether hospital volume affects outcome of patients undergoing hepatobiliary surgery, and whether the centralization of such procedures is justified remains to be investigated. The aim of this study was to analyze the outcome of liver surgery in Italy in relationship of hospital volume. METHODS: This is a nationwide retrospective observational study conducted on data collected by the National Italian Registry "Piano Nazionale Esiti" (PNE) 2023 that included all liver procedures performed in 2022. Outcome measure were case volume and 30-day mortality. Hospitals were classified as very high-volume (H-Vol), intermediate-volume (I-Vol), low-volume (L-Vol) and very low-volume (VL-VoL). A review on centralization process and outcome measures was added. RESULTS: 6,126 liver resections for liver tumors were performed in 327 hospitals in 2022. The 30-day mortality was 2.2%. There were 14 H-Vol, 19 I-Vol, 31 L-Vol and 263 VL-Vol hospitals with 30-day mortality of 1.7%, 2.2%, 2.6% and 3.6% respectively (P < 0.001); 220 centers (83%) performed less than 10 resections, and 78 (29%) centers only 1 resection in 2022. By considering the geographical macro-areas, the median count of liver resection performed in northern Italy exceeded those in central and southern Italy (57% vs. 23% vs. 20%, respectively). CONCLUSIONS: High-volume has been confirmed to be associated to better outcome after hepatobiliary surgical procedures. Further studies are required to detail the factors associated with mortality. The centralization process should be redesigned and oversight.

Enhanced recovery after surgery (ERAS) implementation in cytoreductive surgery (CRS) and hyperthermic IntraPEritoneal chemotherapy (HIPEC): Insights from Italian peritoneal surface malignancies expert centers.

BACKGROUND: Cytoreductive surgery (CRS) combined with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is a complex procedure that involves extensive peritoneal and visceral resections followed by intraperitoneal chemotherapy. The Enhanced Recovery After Surgery (ERAS) program aims to achieve faster recovery by maintaining pre-operative organ function and reducing the stress response following surgery. A recent publication introduced dedicated ERAS guidelines for CRS and HIPEC with the aim of extending the benefits to patients with peritoneal surface malignancies. METHODS: A survey was conducted among 21 Italian centers specializing in peritoneal surface malignancies (PSM) treatment to assess adherence to ERAS guidelines. The survey covered pre/intraoperative and postoperative ERAS items and explored attitudes towards ERAS implementation. RESULTS: All centers completed the survey, demonstrating expertise in PSM treatment. However, less than 30 % of centers adopted ERAS protocols despite being aware of dedicated guidelines. Preoperative optimization was common, with variations in bowel preparation methods and fasting periods. Intraoperative normothermia control was consistent, but fluid management practices varied. Postoperative practices, including routine abdominal drain placement and NGT management, varied greatly among centers. The majority of respondents expressed an intention to implement ERAS, citing concerns about feasibility and organizational challenges. CONCLUSIONS: The study concludes that Italian centers specialized in PSM treatment have limited adoption of ERAS protocols for CRS ± HIPEC, despite being aware of guidelines. The variability in practice highlights the need for standardized approaches and further evaluation of ERAS applicability in this complex surgical setting to optimize patient care.

The clinicopathological features of lung metastases of parathyroid cancinoma.

Parathyroid carcinoma(PC) is an extremely rare malignant tumor of the parathyroid glands. The lung is the most common target organ for PC distant metastases. In this study, twelve patients diagnosed with PC with lung metastases were enrolled in the study. Hematoxylin and Eosin(H&E) stained, immunohistochemical stained and next-generation sequencing (NGS) of a 425-gene panel were performed on tumor tissue samples. At the same time, we also evaluated its histopathologic characteristics. The results indicate that the microscopic examination of metastatic lesions reveals the same structure and characteristics as PC; the tumor was composed of relatively uniform cells organized in nests and separated by thin fibrous bands and abundant blood vessels. Immunohistochemical evaluation of Ki67, CyclinD1, PTH, SYN, CgA, and CD56 was useful in diagnosing PC with lung metastases. The most frequently genetic alterations were mutations of CDC73 and copy number variation (CNV) of MCL1, with a mutation rate of 25 %. In addition, the mutations of CDC73, ATM, TP53, ALK, ERBB2, MAP3K4, TSC1, CCND1 and CNV of CDK4, MCL1, SMARCB1 overlap between metastatic lesions and primary lesions. In conclusions, PC is a rare endocrine malignant tumor that is very difficult to diagnose preoperatively and prone to clinical recurrence or distant metastasis. Genetic mutations, presentation and histological characteristic were the basis for diagnosing PC with lung metastases.