Search Results (26)

Pleural malignancies represent a clinically devastating group of oncological disorders, most commonly arising from metastatic disease, with lung and breast cancers being the most frequent primary sites. Malignant pleural mesothelioma is a primary malignancy of the pleura and occurs less often than metastatic pleural disease. Pleural malignancies often present with malignant pleural effusion, which typically indicates advanced-stage disease and is associated with poor overall prognosis. Treatment of pleural malignancies includes both palliative and definitive approaches. Palliative interventions primarily aim to relieve symptoms and improve quality of life. Definitive treatments include systemic chemotherapy, targeted therapy, and immunotherapy, depending on the type and molecular profile of the underlying tumor. In mesothelioma, platinum-based chemotherapy in combination with pemetrexed remains the cornerstone of treatment, while the combination of nivolumab and ipilimumab is recommended as first-line therapy for unresectable disease. For metastatic disease, systemic therapy is typically tailored to the primary tumor’s characteristics. Intrapleural administration of chemotherapeutic agents is one of the therapeutic strategies and hyperthermic intrathoracic chemotherapy and pressurized intrathoracic aerosol chemotherapy are the most recent innovations that are under active investigation. This review provides an up-to-date synthesis of systemic chemotherapy strategies for pleural malignancies, their integration with targeted and immune-based therapies, and recent advances in intrapleural chemotherapy modalities. It also explores existing knowledge gaps and outlines directions for future research and potential changes in clinical practice. Full article

Background/Objectives: Thymic epithelial tumors with pleural metastasis require a multimodal treatment approach with the use of novel modalities such as hyperthermic intrathoracic chemotherapy (HITHOC). This systematic review and case report aims to summarize the existing evidence regarding HITHOC for these tumors and presents the first case of a robotic approach to HITHOC. Methods: A search in November 2023 yielded a total of 17 articles, including 281 patients who met the eligibility criteria (i.e., underwent HITHOC for treatment of a thymic epithelial tumor). Results: Variations existed among HITHOC regimens and surgical approaches. The most common complications observed were air leaks. Overall survival ranged 92–95% at 1 year, 83–91.7% at 3 years, 66.7–92% at 5 years, 40–83.3% at 10 years, and 27.8–58.2% at 15 years. Conclusions: While HITHOC for thymic epithelial tumors with pleural dissemination has been shown to yield successful outcomes in the literature, this procedure has historically been performed almost exclusively via an open thoracotomy. The robotic approach to HITHOC is feasible and affords several important benefits. Full article

Pressurized intra-thoracic aerosol chemotherapy (PITAC) is a novel and promising strategy for the treatment of malignant pleural effusion (MPE). PITAC enables effective pleurodesis while potentially exerting an antineoplastic effect by delivering chemotherapeutic agents as a therapeutic aerosol into the thoracic cavity via a nebulizer. Our preliminary study involved nine patients with unresectable pleural mesothelioma (PM) treated with PITAC. Among them, one case was particularly emblematic for demonstrating notable oncological improvements in addition to well-known palliative benefits. This patient underwent two PITAC procedures, one year apart, without perioperative complications. Redo pleural biopsies from both previous and new sites revealed only fibrous tissue and inflammatory cells, with no evidence of malignancy. Beyond achieving pleurodesis, PITAC—by combining cytotoxic and sclerosing effects—may offer effective local antineoplastic control and represent a promising avenue for enhancing loco-regional therapy in PM. Full article

Malignant Triton Tumors (MTTs) are rare, high-grade malignant peripheral nerve sheath tumors (MPNSTs) frequently associated with Type 1 Neurofibromatosis (NF1). NF1, an autosomal dominant disorder, predisposes approximately 10% of affected individuals to developing MPNSTs, with 50% of these tumors occurring in NF1 patients, while others arise sporadically or in association with radiation exposure. MTTs predominantly affect anatomical regions rich in large nerves, such as the limbs, spinal root, and cranial nerves. Mediastinal presentations are exceedingly rare, posing significant diagnostic and therapeutic challenges. Current treatment strategies include surgical resection, chemotherapy, radiotherapy, and lung-sparing procedures for metastatic disease. Molecular studies of MPNSTs have revealed that NF1 mutations lead to dysregulation of the RAS signalling pathway, while epigenetic alterations (e.g., SUZ12/EED mutations) further contribute to tumor progression. Dysregulated phylogenetically conserved pathways, including Wnt/beta-catenin and non-canonical SHH signalling, play a role in sarcoma progression and Schwann cell transformation. Recent advances in miRNA research highlight their involvement in tumor invasion and progression, with dysregulated miRNA expression and chromatin remodeling contributing to the pathogenesis of these neoplasms. However, the distinct molecular profiles for MTTs remain incompletely understood. Further investigation of the genetic and epigenetic landscape is essential for improving our understanding and identifying potential therapies. Herein, we present a single-center retrospective case series of three patients with an intrathoracic triton tumor treated at our University Hospital between 2000 and 2024, serving as a starting point for future insights into MPNST pathobiology. Full article

Pleural carcinomatosis (PC) and malignant pleural effusion (MPE) affect up to 20% of patients with non-small cell lung cancer (NSCLC) and are usually synonymous with poor prognosis. Pressurized Intra-Thoracic Aerosol Chemotherapy (PITAC) is a novel and promising technique to control MPE in PC-NSCLC. This pilot study aimed to assess the feasibility, safety, and efficacy of PITAC in terms of palliative pleurodesis and evaluate the local antineoplastic control by analyzing patient-derived primary cell cultures. From January to December 2023, seven patients underwent PITAC with tailored doses of cisplatin and doxorubicin. There were four males and three females, with a median age of 65 (IQR:19) years. No operating room contamination by aerosolized chemotherapeutics was observed. No intraoperative complications occurred, and 30-day mortality was nil. One patient developed a postoperative prolonged air leak. The median chest tube stay was 2 (IQR:2) days, and the median hospital stay was 4 (IQR:2) days. No systemic toxicity nor hypersensitivity to chemotherapeutics were observed. All patients developed effective pleurodesis in 30 days. Cell cultures obtained from biopsy of PC-NSCLC sampled before PITAC formed confluent and monolayer sheets of attached tumor cells, while after 30 min from PITAC, cultures exhibited a significant reduction in the cancer cells’ growth. Effective pleurodesis was observed three and six months after surgery in all patients. PITAC is a safe and effective technique to control MPE recurrence and might revolutionize loco-regional therapy for PC-NSCLC. Further research should assess its oncological role. Full article

Objectives: Extensive-stage small-cell lung cancer (SCLC) has a poor prognosis, but recently, the combination of immunotherapy and chemotherapy has improved treatment outcomes in some patients, and treatment plans may vary depending on the individual’s general condition and tumor response. In addition, intrathoracic tumor control remains a major challenge for this disease. In the current study, we aim to share our clinical experience and demonstrate that consolidative high-dose thoracic radiotherapy effectively reduces intrathoracic tumor recurrence while maintaining acceptable treatment-related toxicities. Materials and Methods: The medical records of 81 SCLC patients treated at Korea University Guro Hospital from January 2019 to December 2023 were reviewed retrospectively. Among them, 22 patients with extensive-stage SCLC who had a favorable tumor response after systemic therapy, including those with oligo-progressive disease limited to the thoracic region and suitable for curative local therapy, received consolidative radiotherapy. A total dose of 52.5 Gy in 25 fractions was administered over 5 weeks to all patients with extensive-stage SCLC. Results and Conclusions: The median follow-up time was 22 months (range: 8–59 months), with the median follow-up period after completing consolidative radiotherapy being 13 months (range: 4–35 months). In-field local recurrence occurred in only one patient after consolidative thoracic radiotherapy. Most importantly, 10 patients with oligo-progressive disease at the thoracic site, at the time of tumor response, remained stable without further intrathoracic in-field recurrence. Additionally, no severe cases of radiation pneumonitis or esophagitis were observed. Based on our institution’s experience, consolidative high-dose thoracic radiotherapy is well-tolerated and associated with fewer intrathoracic recurrences, leading to improved long-term survival in carefully selected patients with extensive-stage SCLC. Given these findings, we believe consolidative radiotherapy should be considered more proactively in clinical practice. Furthermore, these results may help guide the design of future clinical trials. Full article

Pleural mesothelioma (PM) is an aggressive cancer originating from the mesothelial lining of the pleura, with a rising global incidence since the mid-20th century due to asbestos and erionite exposure. PM accounts for 80–90% of all mesothelioma cases and is histologically classified into three subtypes—epithelioid, sarcomatoid, and biphasic— with epithelioid carrying the most favorable prognosis. Despite advances in surgery, chemotherapy, radiotherapy, and immunotherapy, PM prognosis remains poor, necessitating more effective, multimodal strategies. Hyperthermic intrathoracic chemoperfusion (HITHOC) has emerged as a promising adjunct to cytoreductive surgery by delivering heated chemotherapy directly to the pleural cavity, potentially improving survival—especially in patients with epithelioid PM. Combining HITHOC with post-surgical immunotherapy represents a novel approach to enhancing both local and systemic anti-tumor responses and targeting microscopic disease and distant metastases. This review explores surgical outcomes after surgery for PM, the therapeutic synergy of HITHOC and immunotherapy, ongoing clinical trials evaluating this multimodal strategy, and its implications for future patient care. Full article

Background: Immune checkpoint inhibitors (ICIs) offer a novel approach to cancer treatment by enhancing immune responses against malignant cells. However, ICIs are associated with immune-related adverse events (irAEs), including hyponatremia, a potentially severe electrolyte disturbance. The risk of hyponatremia increases further when ICIs are combined with cisplatin, a nephrotoxic chemotherapy agent widely used in treating respiratory and intrathoracic cancers. This study investigated the incidence, severity, and temporal dynamics of hyponatremia in patients treated with ICIs alone or in combination with cisplatin. Methods: A retrospective cohort study was conducted using data from the TriNetX global health research network. Patients with respiratory or intrathoracic malignancies (n = 14,026) were divided into two groups: ICI-only (n = 7013) and ICI with cisplatin combination (n = 7013), matched using propensity scores. Hyponatremia was categorized into mild (130–134 mmol/L), moderate (125–129 mmol/L), and severe (<125 mmol/L). Temporal trends and cumulative incidence over 90 days were analyzed using Poisson regression. Results: The combination group exhibited a higher cumulative incidence of hyponatremia across all severity levels, with early-phase risk peaking within 20 days of treatment. Rate ratios for mild, moderate, and severe hyponatremia were significantly elevated in the combination group (p < 0.01). Conclusions: Hyponatremia is a significant complication in patients receiving ICIs, particularly when combined with cisplatin. Early monitoring and tailored management are essential to mitigate risks and optimize treatment outcomes. Full article

Background: Preclinical studies on liposomal interleukin (IL) therapy demonstrate considerable promise in cancer treatment. This review explores the achievements, challenges, and future potential of liposomal IL encapsulation, focusing on preclinical studies. Methods: A structured search was conducted using the PubMed and Web of Science databases with the following search terms and Boolean operators: (“liposomal interleukin” OR “liposome-encapsulated interleukin”) AND (“gene therapy” OR “gene delivery”) AND (“cancer” OR “tumor” OR “oncology”) AND (“pre-clinical studies” OR “animal models” OR “in vitro studies”. Results: Liposomal IL-2 formulations are notable for enhancing delivery and retention at tumor sites. Recombinant human interleukin (rhIL-2) adsorbed onto small liposomes (35–50 nm) substantially reduces metastases in murine models. Hepatic metastasis models demonstrate superior efficacy of liposomal IL-2 over free IL-2 by enhancing immune responses, particularly in the liver. Localized delivery strategies, including nebulized liposomal IL-2 in canine pulmonary metastases and intrathoracic administration in murine sarcoma models, reduce systemic toxicity while promoting immune activation and tumor regression. Liposomal IL gene therapy, delivering cytokine genes directly to tumor sites, represents a notable advancement. Combining IL-2 gene therapy with other cytokines, including IL-6 or double-stranded RNA adjuvants, synergistically enhances macrophage and T-cell activation. Liposomal IL-4, IL-6, and IL-21 therapies show potential across various tumor types. Pairing liposomal IL-2 with chemotherapy or immune agents improves remission and survival. Innovative strategies, including PEGylation and ligand-targeted systems, optimize delivery, release, and therapeutic outcomes. Conclusions: Utilizing immune-stimulatory ILs through advanced liposomal delivery and gene therapy establishes a strong foundation for advancing cancer immunotherapy. Full article

Background: Primary intrathoracic synovial sarcoma (SS) is a rare entity. The objective of this study was to evaluate survival outcomes for patients with intrathoracic SS presenting with localized disease at diagnosis. Methods: We conducted a retrospective review of 63 patients diagnosed with intrathoracic SS between 1997 and 2020. The Kaplan–Meier method and log-rank test were used to estimate the progression-free survival (PFS), overall survival (OS), local recurrence-free survival (LRFS), and metastasis-free survival (MFS). The hazard ratios were estimated by using Cox proportional hazards regression. Median follow-up time, age-at-diagnosis, and primary tumor size were 31 months (range: 4–218 months), 43 years (range: 18–77), and 7 cm (range: 1–23), respectively. Results: Sixty-two of sixty-three (98%) patients had their primary tumor resected, from whom eighteen (29%) and forty-three (69%) had received neo/adjuvant radiotherapy and chemotherapy, respectively. Median PFS, OS, and MFS were 1.2, 3.0, and 1.1 years, respectively. Based on multivariable analyses, patients with ≥5 cm tumor size had poorer OS (versus < 5 cm; HR: 2.66; 95% CI: 1.16, 6.11; LR-p = 0.014). Importantly, the receipt of neo/adjuvant chemotherapy was the only factor associated with both a more favorable PFS (HR: 0.33; 95% CI: 0.17, 0.65; LR-p = 0.0002) and a more favorable MFS (median 1.33 years versus no chemo 0.5 years; HR: 0.35; 95% CI: 0.17, 0.73; LR-p = 0.005). Conclusions: Outcomes associated with intrathoracic SS remain poor. Factors associated with poorer outcomes include larger tumors and omission of chemotherapy in the management of localized disease. We recommend providing perioperative chemotherapy to all patients with ≥5 cm tumor size to improve progression and metastasis-free survival. Full article

Background: Hyperthermic intrathoracic chemotherapy (HITOC) is an additive treatment option after surgical cytoreduction of pleural malignancies. Despite growing clinical experience and studies evaluating its feasibility, postoperative morbidity and mortality, as well as the effect on survival, there is still only little known about the local effects of HITOC on the lung parenchyma and tumour cells. The objective of this in vitro study was to evaluate the dose-dependent concentration and penetration depth of cisplatin in human lung tissue. Methods: In total, 40 patients were enrolled for elective lung resection, and wedge samples were taken to the laboratory. The visceral pleura was removed, and the decorticated lung tissue was incubated in cisplatin solutions of different concentrations (0.05, 0.075, and 0.1 mg/mL) at 42 °C over 60 min. Afterwards, platinum amounts in the lung tissue samples were measured using atomic absorption spectroscopy. Results: A strong decline of the cisplatin concentration was found until a depth of 3.5 mm, followed by a mild decline until a depth of 7.5 mm. In a depth of 0.5 mm, there was only a significant difference between 0.05 and 0.1 mg/mL (p = 0.03, Cohen’s d = 0.43). In a depth of 1.5 mm, there was an overall significant difference in cisplatin concentration dependent on dose (p = 0.027). In deeper tissue layers, no significant difference in cisplatin concentrations in the tissue was found. Conclusions: A dose-dependent increase of the cisplatin concentration was found for superficial tissue layers. This emphasises the relevance of sufficiently high intrathoracic concentrations of the chemotherapeutic agent. This study confirms that cisplatin penetrates lung tissue in therapeutically effective concentrations. Full article

Background: Extensive-stage small-cell lung cancer (ES-SCLC) treatment has recently been revolutionized by the advent of immune checkpoint inhibitors. This survey was conducted to evaluate the current pattern of care among Italian clinicians, in particular about the integration with radiation therapy (RT). Methods: In June 2023, 225 Italian cancer care professionals were invited to complete a 21-question web-based survey about ES-SCLC management through personal contacts and the Italian Association for Radiotherapy and Clinical Oncology (AIRO) network. Results: We received 90 responses; the majority were radiation oncologists (89%) with more than 10 years of experience (51%). The preferred management of ES-SCLC in patients with a good performance status was concomitant chemo-immunotherapy (84%). Almost all respondents recommended prophylactic cranial irradiation (PCI) (85%), taking into account age and thoracic response; PCI was performed mainly between the end of chemotherapy and before starting immunotherapy (37%), with a three-dimensional conformal technique (46%). Furthermore, 83% of respondents choose to deliver thoracic RT in the case of both an intrathoracic and extrathoracic response, with an RT schedule of 30 Gy/10 fractions. Stereotactic RT is increasingly being used in oligoprogressions. Conclusions: Our analysis showed the variability of real-world management of ES-SCLC. Future clinical trials and developments are needed to improve the multidisciplinary treatment of these patients. Full article

Fibrolamellar hepatocellular carcinoma (FL-HCC) is a malignant primary hepatic cancer that affects mainly adolescents and young adults without underlying liver disease. Its biology remains unknown, but it is pathologically distinct from traditional HCC. Therapeutic strategies are not well defined and, as chemotherapies seem to have limited efficacy, surgical resection remains the only effective treatment. Here we report on a case of a metastatic FL-HCC in an 18-year-old man successfully treated with aggressive intra-thoracic bilateral lung metastasectomy following primary tumour resection and adjuvant chemotherapy. Survival time after initial hepatectomy is 39 months, with no recurrence of disease to date. Aggressive surgical resection and redo surgery should be considered until more effective multimodality therapies are identified. Multidisciplinary team discussion and involvement of medical and surgical specialties are essential in managing these rare entities. Full article

Pleural mesothelioma (PM) is a rare but aggressive thoracic tumor with a poor prognosis. Multimodal treatment—including induction chemotherapy, aggressive surgical resection, radiotherapy and immunotherapy in selected cases—currently represents the best therapeutic option. Single-center studies advocate hyperthermic intrathoracic chemotherapy (HITHOC) during surgical resection as an additional therapeutic option, although its impact on post-operative morbidity and survival has not yet been evaluated on a larger scale. HITHOC can be applied not only in the case of mesothelioma, but also in the case of thymoma with pleural involvement or—in very selected cases—in patients with secondary pleural metastases. Despite favorable outcomes and reduced clinical risks, there is no uniform approach to HITHOC, and a wide variety of indications and technical applications are still reported. Based on available data, HITHOC seems to offer a clear benefit in regard to overall survival of all mesothelioma patients; however, multicenter randomized controlled trials are required to validate and standardize this approach. The aim of this review is to focus on the present role of HITHOC in thoracic tumors with pleural involvement as well as on future challenges, particularly in the light of possible combined therapy of thoracic tumors still presenting poor prognoses. Full article

(1) Background. Intracavitary hyperthermic chemotherapy (HITHOC) remains part of the complex mosaic that is the multimodal approach for advanced stage thymoma and pleural malignancies. However, robotic pleurectomy/removal of pleural lesions in combination with intrathoracic chemotherapy is not currently being investigated. The aim of this study is to evaluate the safety of robotic pleurectomy/removal of relapses and HITHOC in patients with pleural recurrence of thymoma or MPM. (2) Methods: The data of nine consecutive patients affected by thymoma relapses or MPM who underwent robotic surgery in combination with HITHOC from February 2017 to November 2022 were collected and analyzed. Surgery performed prior to intrathoracic infusion of high-temperature chemotherapy consisted of removal of recurrences (three patients) or pleurectomy (six patients). All surgeries were performed with a four-port, fully robotic technique. (3) Results: No intraoperative complications occurred. No renal complications related to infusion were recorded. One patient, who underwent pleurectomy for MPM, had a grade II Clavien–Dindo postoperative complication. Oncological follow-up showed results in line with the literature. (4) Conclusions: With the limitation of the small number of patients, robotic surgery in combination with HITHOC seems to be safe in patients with pleural relapses of thymoma and early-stage MPM. Full article