Clinical benefit and tolerability of adjuvant intraperitoneal chemotherapy in patients who have or have not received neoadjuvant chemotherapy for advanced ovarian cancer.

BACKGROUND: Adjuvant chemotherapy using intraperitoneal (IP) treatment has demonstrated survival benefit over intravenous (IV) therapy alone in patients treated with upfront debulking surgery for advanced stage ovarian cancer. Neoadjuvant chemotherapy followed by interim surgery and adjuvant chemotherapy has similar outcome in survival as compared to upfront surgery followed by adjuvant IV chemotherapy. IP chemotherapy has not been widely adopted in clinical practice for a number of reasons. Whether IP chemotherapy delivered in the patients who received neoadjuvant chemotherapy can be well tolerated or confers any clinical benefit has not been well studied. AIM: To evaluate the experience of adjuvant IP chemotherapy in the community cancer clinic setting, and the clinical benefit and tolerability of incorporating IP chemotherapy in patients who received neoadjuvant treatment. METHODS: We retrospectively evaluated toxicities and outcomes of patients with stage III and IV ovarian cancer diagnosed at our institution between 07/2007 and 07/2015 who received intraperitoneal chemotherapy after cytoreductive surgery (group 1) or after neoadjuvant chemotherapy followed by interim surgery (group 2). RESULTS: Thirty eight patients were treated with IP chemotherapy, median age was 54 years old (range 38.6 to 71 years). In group 1 (n = 25), 12 (48%) of the patients completed 4 or more cycle of IP treatment after upfront debulking surgery; while in group 2 (n = 13), 8 (61.5%) of the patients completed all 3 cycles of the assigned IP chemotherapy after receiving neoadjuvant IV chemotherapy followed by surgery, and 2 (15.4%) more patients tolerated more than 3 cycles. In those patients who did not get planned IP chemotherapy, most of them were treated with substitutional IV chemotherapy, and the completion rate for 6 cycles of IV + IP was 92%. Abdominal pain, (64% in group 1 and 38% in group 2), vomiting, (36% in group 1 and 30.8% in group 2), dehydration (16% in group 1 and 15.4% in group 2), and hypomagnesemia (12% in group 1 and 15.4% in group 2) were the most common adverse effects in all patients, while patients who have received neoadjuvant chemotherapy were more likely to get hypokalemia, fatigue and renal insufficiency. Progression free survival (PFS) was 26.5 mo (95% CI 14.9, 38.0) in group 1 and 27.6 mo (95% CI 13.1, 42.1) in group 2. The overall survival was 100.2 mo (95% CI 67.9, 132.5) for group 1 and 68.2 mo (95% CI 32.2, 104.0) for group 2. For the entire cohort, PFS was 26.5 mo (95% CI 15.9, 37.0) and OS was 78.8 mo (95% CI 52.3, 105.4). CONCLUSION: The use of IP/IV chemotherapy can be safely administrated in the community cancer clinic setting. The use of IP/IV chemotherapy in patients who have received neoadjuvant chemotherapy followed by surgery is feasible and tolerable. Despite various modification of the IP regimen, incorporation of IP chemotherapy in the adjuvant setting appears to be associated with improved PFS and overall survival.

Response of advanced stage recurrent lymphoepithelioma-like carcinoma to nivolumab.

Lymphoepithelioma-like carcinoma (LELC) of lung is a rare tumor that is mostly reported in south-east Asian countries. The surgical removal is curative in the early stages but there is no consensus on the choice of chemotherapy for the treatment of advanced stage tumors. Most of the data on chemotherapy are based on small case series and retrospective studies. As per available data, this tumor responds to chemotherapy initially but recurrences are common. The use of conventional chemotherapy in recurrent tumors leads to cumulative toxicities in the long term. Due to lack of actionable mutations, targeted therapies are also not very useful. Immune check point inhibitors immune checkpoint inhibitors have shown survival benefit in patients with advanced stage non-small-cell and small cell carcinoma with better side effect profile than conventional chemotherapy. The role of immune checkpoint inhibitors in LELC is unknown. Though several studies have reported high expression of programmed cell death-1 (PD-1)/or its -ligand (PD-L1) in LELC providing a rationale for trial of these agents, the actual benefit of these agents in LELC has not been reported so far. In this case series, we report two cases of advanced stage LELC that progressed despite multiple lines of chemotherapy but responded favorably to a PD-1 inhibitor, nivolumab.

Unusual Presentation of Diffuse Large B-Cell Lymphoma With Splenic Infarcts.

A 67-year-old man presented with a 3-day history of abdominal pain, fever, and significant weight loss over 2 months. Physical examination revealed left upper quadrant tenderness, hepatomegaly, splenomegaly, and bilateral pitting edema but peripheral lymphadenopathy was absent. Laboratory tests showed anemia, thrombocytopenia, elevated prothrombin time (PT), partial thromboplastin time (PTT), and increased lactate dehydrogenase (LDH). PTT was corrected completely in mixing study. Further workup for the cause of coagulopathy revealed decreased levels of all clotting factors except factor VIII and increase fibrinogen levels, which ruled out disseminated intravascular coagulation (DIC). Flow cytometry of peripheral blood was normal. Contrast-enhanced computed tomography (CECT) revealed splenomegaly with multiple splenic infarcts without any mediastinal or intraabdominal lymphadenopathy. Further investigations for infective endocarditis (blood cultures and transthoracic echocardiography) and autoimmune disorders (ANA, dsDNA, RA factors) were negative. The patient received treatment for sepsis empirically without any significant clinical improvement. The diagnosis remained unclear despite extensive workup and liver biopsy was conducted due to high suspicion of granulomatous diseases. However, the liver biopsy revealed high-grade diffuse large B-cell lymphoma (DLBCL). Unfortunately, patient died shortly after the diagnosis. Here we report a case of high-grade DLBCL with hepatosplenomegaly and splenic infarcts in the absence of any lymphadenopathy or focal lesions. This case highlights the fact that unusually lymphoma can present in the absence of lymphadenopathy or mass lesion mimicking autoimmune and granulomatous disorders. The diagnosis in these cases can only be made on histology, and hence the threshold for biopsy should be low in patients with unclear presentations and multiorgan involvement.