Clinical activity of pembrolizumab in refractory MDM2-amplified advanced intimal sarcomas.

Intimal sarcoma (InS) is an ultra-rare and aggressive subtype of soft tissue sarcoma (STS). It usually arises in large mediastinal arteries and the heart. In the advanced setting, sequential cytotoxic chemotherapy is often used, mainly based on retrospective studies and case series but with modest benefit. The use of immune checkpoint inhibitors is a promising strategy for some STS, but identifying biomarkers of response remains challenging due to disease rarity and heterogeneity. A reactive and pro-inflammatory tumor microenvironment (TME) is believed to be associated with better outcomes for patients receiving anti-PD-1-based regimens, generating the rationale to explore this strategy in malignancies with this characteristic, such as InS. We report three cases of advanced InS patients experiencing partial response to pembrolizumab-based therapy despite low tumor mutational burden and absence of mismatch-repair deficiency. We hypothesize that TME-related characteristics such as PD-L1 expression and the presence of tertiary lymphoid structures might explain this phenomenon.

Pembrolizumab in advanced intimal sarcomas Intimal sarcomas are ultra-rare and highly aggressive malignant tumours that most frequently arise in mediastinal arteries or the heart. Besides arising in challenging areas of the thoracic cavity, their rarity directly interferes with the development of new therapies, which negatively impacts patients' prognosis, especially after disease progression on chemotherapy regimens. We reported three cases successfully treated with immunotherapy (represented by pembrolizumab-based regimens), as well as a potential explanation for their outcomes.

Clinico-demographic characteristics and outcomes of radiation-induced sarcomas (RIS): a CanSaRCC study.

Background: Radiation-induced sarcomas (RIS) tend to have aggressive behaviour and because of their rarity, the most appropriate management for these malignancies is uncertain. Objectives: Using the Canadian Sarcoma Research and Clinical Collaboration (CanSaRCC) database, a national sarcoma registry, we aimed to investigate prognostic factors and outcomes for RIS. Design: Retrospective study of RIS patients treated from 1996 to 2021 at three Canadian centres. Methods: RIS was defined as a sarcoma arising in a previously irradiated field following a 3+ year latency period, whose histology was distinct from the initially irradiated tumour. Clinicopathologic and treatment-related information was extracted from the CanSaRCC database. Overall survival (OS) was defined as the time from RIS diagnosis to death from any cause. Response rate (RR) to neoadjuvant chemotherapy (NACT) was based on physician assessment. Time-to-event analyses were estimated using the Kaplan-Meier method, with Cox regression for multivariate analysis. We considered a two-tailed p-value of <0.05 as statistically significant. Results: One hundred seven tumours met the criteria for RIS and were divided into three subgroups: breast angiosarcoma (BAS, n = 54), osteosarcoma (OST, n = 16), and other soft-tissue sarcomas (STS, n = 37). Patients were mostly female (n = 85, 79%), treated initially for breast carcinomas (n = 54, 50.5%), and diagnosed with high-grade tumours (n = 61/71, 86%). None had evidence of synchronous metastasis. Patients with OST were younger (median age: 48 years, p < 0.001), and BAS had the shortest latency interval (8 versus 18 years for OST/STS, p < 0.001). Most patients underwent surgery, 76% (n = 76/100) R0; 24% (n = 26) received radiation therapy, mostly (n = 15, 57.7%) neoadjuvant. Among those receiving chemotherapy, 30 (75%) underwent NACT; among patients with documented response assessment, the RR was 68% (n = 17/25), being even higher in the BAS population (89.5%, n = 13/17). Median OS was 53 months (95% CI 34-101), with a 5-year OS of 47.6%; larger tumour size, high histologic grade and older age were independent prognostic factors for worse OS. Conclusion: Surgery is standard, and NACT might be useful to downsize large lesions, especially in BAS patients. Raising RIS awareness is fundamental to promoting appropriate management and fostering research through multi-institutional collaborations.

Characterization and outcomes of patients enrolled to multiple phase I cancer trials.

PURPOSE: Some patients who participate in early phase cancer trials enroll to more than one trial. Whether these patients have different characteristics or outcomes than patients who enroll to a single phase I trial is unknown. METHODS: The study included all patients who participated in the solid tumor drug development program of the Princess Margaret Cancer Centre, a specialized academic cancer center, from July 2014 to January 2017. Patients sequentially enrolled to multiple phase I trials were compared to those enrolled in a single trial according to demographics, clinical characteristics, reported toxicities and prognosis. RESULTS: The study cohort included 328 patients, including 61 (19%) enrolled to multiple phase I trials and 267 (81%) enrolled to a single phase I trial. Demographics, comorbidities, performance status, cancer site and time between initial diagnosis and initial enrollment to the phase I program were comparable between both groups. Patients enrolled to multiple phase I trials received more previous non-trial treatment lines (median 3 versus 2, p < 0.001) and had a higher average response rate on phase I trials (18% versus 10%, p = 0.03). Toxicity data, including number of any adverse events (AEs), grade 3/4 AEs, serious AEs and dose-limiting toxicities were comparable between both groups. Time to disease progression and time to last documented follow-up were also comparable between both groups. CONCLUSIONS: Patients enrolled to multiple phase I trials and those enrolled to a single trial had similar toxicity and prognostic profiles. These patients do not introduce bias into early-phase cancer trials results.

Prognostic and predictive value of CA-125 in the primary treatment of epithelial ovarian cancer: potentials and pitfalls.

The serum cancer antigen 125 (CA-125) remains a reliable biomarker in the therapeutic management of epithelial ovarian cancer (EOC). Monitoring the efficacy of cytotoxic chemotherapy (CT) and the early detection of relapse during the follow up of patients in remission represent the two most common clinical situations where the CA-125 has been successfully applied. There are however other scenarios along the course of the disease where the CA-125 can potentially aid in the decision-making process. Preoperative levels of CA-125 can help in selecting a subset of patients where an optimal cytoreduction may not be easily achieved. Perioperative variations in the CA- 125 levels after primary surgery and, more importantly, the nadir value of the CA-125 after primary chemotherapy, are associated with patient outcome. This review focuses on the clinical relevance of dynamic changes in CA-125 levels during the primary treatment of EOC and its potential influence both in the patient management and in the design of clinical trials in the adjuvant setting.

Carboplatin and pemetrexed in the management of malignant pleural mesothelioma: a realistic treatment option?

BACKGROUND: Malignant pleural mesothelioma is an aggressive cancer. Chemotherapy with cisplatin and pemetrexed can improve overall survival but has a toxic profile. Substitution of cisplatin with carboplatin may avoid some potential side-effects. Therefore, we undertook a retrospective review to assess the effectiveness and tolerability of carboplatin and pemetrexed in patients with malignant pleural mesothelioma in clinical practice. METHODS: Patients with malignant pleural mesothelioma who had been treated with carboplatin and pemetrexed were retrospectively identified from pharmacy databases. The endpoints were disease control rate, time to treatment failure, clinical improvement rate and overall survival. We also evaluated any significant haematological and non-haematological toxicities. RESULTS: A total of 49 patients were identified. Of 45 evaluable cases, the disease control rate was achieved in 34 patients (69%, 95% CI 55-82, intention to treat analysis). The clinical response rate was achieved in 34 out of 49 patients (69%, 95% CI 55-82). The median time to treatment failure was 4.6 months (95% CI 3.4-5.8) and median overall survival was 14 months (95% CI 9.5-18.5). Grade 3/4 haematological toxicities were observed in 7 patients (14.3%). Grade 3/4 non-haematological toxicities were seen in 12 patients (24.5%). No toxic deaths were recorded. CONCLUSION: The combination of carboplatin and pemetrexed may be a viable option in the treatment of malignant pleural mesothelioma.

Tracheobronchial amyloidosis: utilization of radiotherapy as a treatment modality.

Tracheobronchial amyloidosis (TBA) is a rare disease. No general consensus exists with regard to its optimal treatment, resulting in a variety of modalities used to manage this condition. In this article, we present a case of TBA treated with external beam radiation therapy with encouraging results. A brief literature review of this rare ailment is also included.

Retreatment with pemetrexed-based chemotherapy in malignant pleural mesothelioma (MPM): a second line treatment option.

The role of second line treatment in malignant pleural mesothelioma (MPM) is currently undefined. We present four cases of patients who had durable responses from pemetrexed-based chemotherapy who were retreated with a similar regimen upon progression of their mesothelioma. This case series explores the possible role of retreatment with pemetrexed-based chemotherapy as a second line therapeutic option in MPM.

Muscular metastasis, a rare presentation of non-small-cell lung cancer.

A 71-year-old man presented with a 2-week history of pain and swelling of his left arm. Subsequent investigations revealed an intramuscular lesion, suggestive of soft tissue sarcoma. Histologic analysis was surprisingly consistent with metastasis from a primary squamous cell lung cancer. Skeletal muscle metastasis as a mode of presentation of primary lung cancer is an unusual phenomenon. A brief literature review accompanies this report.

Medulloblastoma in two successive pregnancies.

A 24-year old primaparous female at 20 weeks gestation presented acutely with cerebellar symptoms. Magnetic resonance imaging brain showed evidence of a cerebellar vermis lesion. This was diagnosed as medulloblastoma on histopathological analysis. She underwent surgical debulking and radiotherapy. Interestingly, the lesion recurred 4 years later on her second pregnancy. She underwent further surgical debulking and adjuvant chemotherapy. We believe this is the first reported description of recurrent medulloblastoma in successive pregnancies. A brief discussion on this disease and its management in pregnancy setting is also presented.