Bidirectional Approach with PIPAC and Systemic Chemotherapy for Patients with Synchronous Gastric Cancer Peritoneal Metastases (GCPM).

BACKGROUND: This study evaluated the efficacy of pressurized intraperitoneal aerosol chemotherapy (PIPAC) with systemic chemotherapy as a bidirectional approach for gastric cancer (GC) patients with synchronous peritoneal metastases (SPM). METHODS: A retrospective analysis of a prospective PIPAC database was queried for patients who underwent a bidirectional approach between October 2019 and April 2022 at two high-volume GC surgery units in Italy (Verona and Siena). Surgical and oncological outcomes were analyzed. RESULTS: Between October 2019 and April 2022, 74 PIPAC procedures in 42 consecutive patients with Eastern Cooperative Oncology Group performance status ≤2 were performed-32 patients treated in Verona and 10 in Siena. Twenty-seven patients (64%) were female and median age at first PIPAC was 60.5 years (I-III quartiles: 49-68 years). Median Peritoneal Cancer Index (PCI) was 16 (I-III quartiles: 8-26) and 25 patients (59%) had at least two PIPAC procedures. Major complications according to the Common Terminology Criteria for Adverse Events (CTCAE; 3 and 4) occurred in three (4%) procedures, and, according to the Clavien-Dindo classification (>3a), one (1%) severe complication occurred. There were no reoperations or deaths within 30 days. Median overall survival (mOS) from diagnosis was 19.6 months (range 14-24), and mOS from first PIPAC was 10.5 months (range 7-13). Excluding cases with very heavy metastatic peritoneal burden, with PCI from 2 to 26, treated with more than one PIPAC, mOS from diagnosis was 22 months (range 14-39). Eleven patients (26%) underwent curative-intent surgery after a bidirectional approach. R0 was achieved in nine (82%) patients and complete pathological response was obtained in three (27%) cases. CONCLUSIONS: Patient selection is associated with bidirectional approach efficacy and feasibility for SPM GC treatment, which may allow potentially curative surgical radicalization in highly selected cases.

Peripheral monocytes and neutrophils predict response to immune checkpoint inhibitors in patients with metastatic non-small cell lung cancer.

We carried out a retrospective cohort study on patients with metastatic non-small cell lung cancer (mNSCLC) to identify the peripheral blood count parameters associated with response to immune checkpoint inhibitors (ICIs). There were 17 males and 15 females. Their median age was 64.5 years (range 20-84). History of smoking was present in 25/32 (78%) patients. Twelve patients received pembrolizumab, 19 patients nivolumab, and one patient nivolumab followed by pembrolizumab. Responses were observed in 19/32 (59%) patients, all partial responses. There was no difference in the distribution of sex, age, and smoking status between responders and non-responders. The median time to response (TTR) was 12 weeks (range 6-24) and the median duration of response (DoR) was 24 weeks (range 7-112). Higher pre-therapy absolute monocyte counts (AMCs) correlated to shorter TTR (p = 0.03), but not to response rate or DoR. Within the group of responders, those with AMCs > 700/mm3 had a significantly shorter median TTR than those with AMCs ≤ 700/mm3 (8 weeks vs 12 weeks; p = 0.048). Although baseline absolute neutrophil counts (ANCs) did not have any prognostic value, ANCs after first dose predicted response to ICI (p = 0.02). Patients with ANCs ≤ 4200/mm3 after first dose were more likely to respond than those with ANCs > 4200/mm3 (OR = 6.8; 95% CI 1.1-41.8; p = 0.05). Analysis of AMC and ANC before and during therapy may, therefore, provide an easy method to identify those mNSCLC patients most likely to benefit from ICI therapy.

Use of broad-spectrum antibiotics impacts outcome in patients treated with immune checkpoint inhibitors.

We carried out a retrospective cohort study on patients with advanced cancer treated with immune checkpoint inhibitors (ICIs) to determine whether antibiotics affect treatment outcome. Sixty consecutive patients were identified, and 17 received systemic antibiotics within 2 weeks before and/or after first dose of ICI. Antibiotic-treated patients were significantly younger (p = 0.0008) and less likely to receive nivolumab (p = 0.08) or had neutrophil:lymphocyte ratio < 5 (p = 0.08). They had a lower response rate (RR) (29.4% vs 62.8%) (p = 0.024) and more inferior progression-free survival (PFS) (p = 0.048). Narrow-spectrum antibiotics did not affect the RR. However, broad-spectrum antibiotics were associated with a lower RR (25% vs 61%) (p = 0.02) and a trend towards longer time to response (median: 14 weeks vs 12 weeks) (p = 0.1). They also had shorter PFS (p = 0.012). Multivariate analysis identified antibiotics as the only factor affecting RR (p = 0.0038) and PFS (p = 0.01). We next examined the 21 patients whose PFS lasted for 12 weeks or more. Five of the 21 patients received broad-spectrum antibiotics within 10 weeks before disease progression. There was a trend towards shorter PFS in these patients (p = 0.1). Finally, antibiotic-treated patients experienced shorter overall survival (OS) (median: 24 months vs 89 months) (p = 0.003). Multivariate analysis found age (p = 0.035) and antibiotics (p = 0.038) to be the only factors affecting OS. Our results point to a detrimental effect of broad-spectrum antibiotics on treatment outcome to ICI therapy.

A rare presentation of acute heart failure secondary to aggressive uterine leiomyosarcoma metastatic to the myocardium initially diagnosed as hypertrophic obstructive cardiomyopathy.

Uterine sarcoma is the cause of 3-9% of all uterine malignant neoplasms and has a 2-fold higher incidence in black women as compared to white women. Cellular atypia and abundant mitoses (≥10 per 10 high power fields) as seen in this patient are associated with an increased risk for metastases. Metastases to the heart are infrequently reported with a handful of cases in the literature. We present a case of a 51-year-old woman with aggressively metastatic uterine leiomyosarcoma causing acute heart failure 4 months after initial presentation.

A rare case of the upper extremity diffuse large B-cell lymphoma mimicking soft tissue sarcoma in an elderly patient.

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma, with about 30% of new cases presenting with extranodal disease. Lesions originating from soft tissues of the upper extremities are extremely rare and may mimic other malignancies like sarcoma. We present a case of an elderly patient with right upper extremity (RUE) mass which was proven to be DLBCL instead of sarcoma. We emphasize the increasing need for investigating new therapeutic options for patients of extreme age and/or with underlying heart disease.

Phase II trial of a single weekly intravenous dose of ranpirnase in patients with unresectable malignant mesothelioma.

PURPOSE: A multicenter phase II trial of ranpirnase (Onconase; Alfacell Corp, Bloomfield, NJ) as a single agent was conducted to further assess the safety and clinical efficacy of this novel antitumor ribonuclease. Patients with unresectable and histologically confirmed malignant mesothelioma (MM) were eligible. PATIENTS AND METHODS: One hundred five patients with Eastern Cooperative Oncology Group performance status 0 to 2 were enrolled onto the study. Thirty-seven percent of patients had not responded to prior chemotherapy. The primary end point of the study was survival. Tumor responses and time to progression were also assessed. The Cancer and Leukemia Group B (CALGB) prognostic group criteria were used to define a treatment target group (TTG). Both the intent-to-treat (ITT) and the TTG populations were analyzed for survival. RESULTS: Median survival times of 6 months for the ITT and 8.3 months for the TTG populations were observed. The 1- and 2-year survival rates were 34.3% and 21.6% for ITT, respectively, and 42% and 26.8% for TTG, respectively. Among the 81 patients assessable for tumor response, four had partial responses, two had minor regressions, and thirty-five experienced stabilization of previously progressive disease. Patients with responses and stable disease demonstrated markedly prolonged survival. Ranpirnase was well tolerated in the majority of patients, and there were no drug-related deaths. CONCLUSION: Ranpirnase demonstrated activity and a tolerable toxicity profile in patients with unresectable MM. The prognostic value of the CALGB groups was confirmed.

Pericardial synovial sarcoma: challenges in diagnosis and management.

INTRODUCTION: Pericardial synovial sarcoma is an extremely rare tumor with poor prognosis. Timely diagnosis and aggressive multimodal management improves patient outcome. We present our experience of diagnosis and management of a young patient with monophasic synovial sarcoma arising from pericardium. CASE: A 27-year-old man presented with dyspnea and cough of three weeks duration. Examination revealed sinus tachycardia, distant heart sounds and elevated jugular venous pressure. Chest X-ray showed widened mediastinum. Transthoracic echocardiogram (TTE) noted large pericardial effusion with tamponade physiology. Therapeutic pericardiocentesis yielded hemorrhagic fluid. Computed tomography (CT) of the chest showed persistent pericardial effusion and a left anterior mediastinal mass. Left anterior thoracotomy, pericardial window and left anterior mediastinotomy were done, revealing a well-encapsulated gelatinous tumor originating from the pericardium. Histology and immunohistochemical profile showed the tumor to be a monophasic synovial sarcoma. Fluorescent in-situ hybridization (FISH) was positive for SS18 (SYT) gene rearrangement on chromosome 18q11, substantiating the diagnosis. Work-up for metastases was negative. Neo-adjuvant chemotherapy with high dose ifosfamide led to substantial reduction in the size of the tumor. The patient underwent surgical resection and external beam radiation therapy (EBRT) post surgery. He had symptom-free survival for 8 months prior to local recurrence. This was managed with left lung upper lobectomy and follow-up chemotherapy with docetaxel. The patient is currently stable with an acceptable functional status. CONCLUSION: In patients with pericardial effusions of unknown etiology, multiple modalities of cardiac imaging must be employed if there is suspicion of a pericardial mass. CT and magnetic resonance imaging (MRI) are useful to evaluate for pericardial thickening or masses in addition to TTE. Treatment of synovial sarcoma is not well established. Surgery is the cornerstone of treatment. In non-resectable tumors, aggressive neo-adjuvant chemotherapy with ifosfamide followed by surgical resection and EBRT may lead to improved outcome.